ASCO releases studies from upcoming annual meeting

ALEXANDRIA, VA USA  (PRESS RELEASE) - 

Important Advances in Treatment for Aggressive Cancers, Surveillance Strategies and Cancer Prevention

The American Society of Clinical Oncology (ASCO) today highlighted seven studies in a presscast from among more than 4,500 abstracts publicly posted online at abstract.asco.org in advance of ASCO's 49th Annual Meeting.

Plenary, late-breaking and other major studies will be presented in on-site press conferences at the Annual Meeting to be held May 31 - June 4, 2013, at McCormick Place in Chicago, Ill. The meeting, based on the theme Building Bridges to Conquer Cancer, is expected to draw approximately 30,000 cancer specialists from around the world. 

“Fifty years of modern oncology has delivered dramatic progress, offering our patients better treatments, more cures and a better quality of life during and after therapy. We‟re also making headway toward preventing cancer from developing in the first place,” said Bruce J. Roth, MD, Chair of ASCO‟s Cancer Communications Committee. “Studies being presented at this year‟s ASCO Annual Meeting embody a new era of precision medicine, in which we‟re taking better aim at vital targets on cancer and immune cells. Several studies also suggest that „less is more‟ for some cancer treatments, sparing patients unnecessary side-effects and costs.”

Studies highlighted in today's presscast include:

Men who are fit in their fifties have a lower risk of developing and dying from common cancers: Findings from a 20-year follow-up study of over 17,000 men indicate that being fit in middle age protects men against developing and dying from lung and colorectal cancers later in life. Researchers observed that even a modest improvement in cardiovascular fitness reduces the risk of dying from cancer by 14 percent.

New immunotherapy is active against a number of advanced cancers: A phase I study of the PD-L1 targeted antibody MPDL3280A reports tumor shrinkage in 21 percent of patients with advanced melanoma and lung, kidney, colorectal, and stomach cancer. Therapy responses are still ongoing for 26 out of 29 patients who have been on the study between 3-15 months.

 

Early trial suggests a combination of two immunotherapy drugs may be better than either drug alone: A phase I trial shows that concurrent treatment with ipilimumab (Yervoy) and the PD-1 targeted drug nivolumab led to substantial tumor shrinkage in roughly half of patients with difficult-to-treat, advanced melanoma. The authors state this is the strongest immunotherapy response observed in this setting to date.

 

Lower-dose radiation is safer and more effective than higher-dose radiation for advanced NSCLC: A phase III trial shows standard-dose radiation therapy (60 Gy) is superior to high-dose (74 Gy) in terms of both treatment effectiveness and survival. Standard-dose was also associated with significantly fewer treatment-related deaths. Many doctors have been using higher dose therapy, expecting better patient outcomes. These results should discourage this approach and reinforce existing recommendations.

 

Surveillance following surgery for cancer recurrences is a safe long-term strategy for patients with stage I seminoma: The largest study to date of men with this common form of testicular cancer finds that 99.6 percent of patients followed on surveillance alone after surgery are alive at 10 years. Roughly half of U.S. men currently undergo chemotherapy and radiation following surgery to improve outcomes; these findings suggest such treatments may not be necessary for most patients.

 

Routine surveillance imaging scans may not be needed for many lymphoma survivors: A large study reports that only 1.5 percent of diffuse large B cell lymphoma (DLBCL) relapses are detected through scheduled CT surveillance scans alone. While CT scans have been a routine part of follow-up care for many years, the great majority of relapses in this study were detected through symptoms, abnormal findings on physical exams or abnormal blood tests.

 

New targeted drug shows promising activity against treatment-resistant CLL in early trial: Final results from a phase I study in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) indicate that treatment with idelalisib, a new PI3K-delta inhibitor, led to tumor shrinkage in half of the patients treated, stalling disease progression by 17 months on average. The encouraging results point to a possible alternative to traditional chemotherapy for delaying CLL progression.

Detailed information about the 2013 ASCO Annual Meeting Press Program is available on ASCO’s Annual Meeting Media Resource Center, including:

 Media registration instructions

 Press briefing schedule at-a-glance

 Press briefing recordings

 Frequently asked questions

 On-site press facility hours and locations

 Print-friendly materials

 General information about the meeting

 Links to helpful reporting resources such as, ASCO‟s CancerProgress.Net and Cancer.Net websites

The Annual Meeting Media Resource Center will be updated frequently leading up to and throughout the Annual Meeting.

Men’s Fitness in Middle Age Protects against Developing and Dying from Cancer Later in Life (Summary includes updated data not included in the abstract) 

Findings from a large, prospective 20-year study indicate that a high level of cardiovascular fitness in middle age reduces men‟s risk of developing and dying from lung and colorectal cancer, two of the most common cancers affecting men. Better fitness also reduces the risk of dying from, though not developing, prostate cancer. 

“While poor fitness is already known to predict future cardiovascular disease, this is the first study to explore fitness as a marker of future cancer risk prognosis,” said lead study author Susan Lakoski, MD, assistant professor of medicine at the University of Vermont. “This finding makes it clear that patients should be advised that they need to achieve a certain fitness level, and not just be told that they need to exercise. And unlike exercise behavior, which relies on patient self-reporting, fitness can be objectively and accurately measured in a clinical setting.”

The study included 17,049 men who had a single cardiovascular fitness assessment as part of a specialized preventive health check-up visit at a mean age of 50 years offered at the Cooper Institute. The fitness test, which is similar to a stress test for heart disease risk, entailed walking on treadmill under a regimen of changing speed and elevation. The men‟s performance was recorded in established units of fitness called metabolic equivalents or METs. Study participants were divided into five groups (quintiles) according to their fitness performance. 

Researchers subsequently analyzed Medicare claims data to identify the participants of this study who had developed lung, colorectal, or prostate cancer – the three most common types of cancer among U.S. men. Over a median follow-up period of 20-25 years, 2,332 men were diagnosed with prostate cancer, 276 were diagnosed with colorectal cancer, and 277 were diagnosed with lung cancer. There were 347 deaths due to cancer and 159 men died of cardiovascular disease.

Researchers found that the risk of being diagnosed with lung or colorectal cancer was reduced by 68 and 38 percent, respectively, in men who were the most fit, relative to those who were the least fit. Fitness did not significantly impact prostate cancer risk. In the analysis, data were adjusted for smoking and other factors, such as body mass index and age.

Among the men who developed cancer, those who were more fit at middle age had a lower risk of dying from all the three cancers studied, as well as cardiovascular disease. Even a small improvement in fitness (by 1MET) made a significant difference in survival ─ reducing the risks of dying from cancer and cardiovascular disease by 14 and 23 percent, respectively.

Another interesting finding was that men who had low fitness had an increased risk of cancer and cardiovascular disease even if they were not obese. This suggests that patients should focus on improving their fitness, regardless of their body weight. Adequate fitness level depends on gender and age. In this study, men who fell in the lowest quintile for fitness achieved less than 13.5 minutes during the treadmill exercise test if they were 40-49 years old, less than 11 minutes if they were 50-59, and less than 7.5 minutes if they were 60 or older.

ASCO Perspective: “This important study establishes cardiorespiratory fitness as an independent and strong predictor of cancer risk and prognosis in men. While more research is needed to determine if similar trends are valid in relation to other cancers and among women, these results indicate that people can reduce their risk of cancer with relatively small lifestyle changes,” said ASCO President Sandra M. Swain, MD, FACP.

This research was supported by the National Cancer Institute.

Relevant Links From Cancer.Net , the oncologist-approved cancer information website from the American Society of Clinical Oncology:  

Cancer.Net Guides to Cancer

Physical Activity and Cancer Risk

Physical Activity: Suggestions and Tips

Abstract #1520: Cardiorespiratory fitness and risk of cancer incidence and cause-specific mortality following a cancer diagnosis in men: The Cooper Center longitudinal study.

Authors: Susan G. Lakoski, Carolyn Barlow, Ang Gao, Laura DeFina, Nina Radford, Steve Farrell, Benjamin Willis, Jeffrey M. Peppercorn*, Pamela S. Douglas, Jarett Berry, Lee Jones; University of Vermont, Colchester, VT; The Cooper Institute, Dallas, TX; UT Southwestern Medical Center, Dallas, TX; The Cooper Clinic, Dallas, TX; Duke Cancer Institute, Durham, NC; Duke University, Durham, NC; Duke University Medical Center, Durham, NC

Background: Few studies have examined the prognostic importance of cardiorespiratory fitness (CRF) to predict cancer incidence or cause-specific mortality following a cancer diagnosis in men. Accordingly, we examined the relationships between baseline CRF and incidence of prostate, lung, or colorectal cancer in men at Medicare age and subsequent cause-specific mortality among men diagnosed with cancer. Methods: The Cooper Center Longitudinal Study (CCLS) is a prospective observational cohort study of participants undergoing a preventive health examination including CRF assessment at the Cooper Clinic in Dallas, Texas. We studied 17,049 men with a complete CCLS medical exam and cardiovascular risk factor assessment at a mean age of 50± 9 years. Cancer incidence was defined using Medicare claims data. Cox proportional models were used to estimate the risk of adjusted primary cancer incidence and cause-specific mortality after cancer according to baseline age-specific CRF quintiles (Q). Results: The mean times from CRF assessment to cancer incidence and death were 20.2 ± 8.2 years and 24.4 ± 8.5 years, respectively. During this period, 2885 men were diagnosed with prostate, lung, or colorectal cancer and 769 died. Compared with men in lowest CRF quintile, the adjusted hazard ratio (HR) for incident lung, colorectal, and prostate cancer incidence among men in the highest CRF quintile was 0.32 (95% CI: 0.20 to 0.51, p<0.001), 0.62 (95% CI: 0.40 to 0.97, p=0.05), 1.13 (95% CI: 0.97 to 1.33, p=0.14), respectively. In men developing cancer, both cancer-specific mortality and cardiovascular-specific mortality declined across increasing CRF quintiles (p‟s <0.001). A 1-MET increase in CRF was associated with a 14% reduction in cancer-specific mortality (HR 0.86, 95% CI: 0.81-0.91, p<0.001), and 23% reduction in cardiovascular-specific mortality (HR 0.77, 95% CI: 0.69-0.85, p<0.001). Conclusions: Fitness is a strong independent predictor of incident lung and colorectal cancer and remained a robust predictor of cause-specific mortality in middle-aged and older men diagnosed with lung, prostate, or colorectal cancer.

Disclosures: Jeffrey M. Peppercorn*, MD, MPH, Employment/Leadership Position with GlaxoSmithKline (I), Consultant or Advisory Role with Bayer, Genentech, Stock Ownership with GlaxoSmithKline (I)

Authors marked with an asterisk (*) are participants in ASCO‟s Disclosure Management System Pilot; their disclosure is not limited to subject matter under consideration in this article and includes payments to themselves, an immediate family member (I), and/or their institutions (Inst). For information on the pilot program, or to provide feedback, please visit coipilot.asco.org .  

Anti-PD-L1 Drug Shows Promising anti-Cancer Effects in a Variety of Advanced Cancers (Summary contains updated data not included in the abstract)

A phase I expansion study of the investigational drug MPDL3280A – an engineered PD-L1 targeted antibody – shows impressive tumor shrinkage rates in patients with several different cancers – including lung, melanoma, kidney, colorectal and gastric cancers – that had progressed despite several prior treatments. The new drug was safe and produced durable responses, with nearly all responses still ongoing. Several patients experienced tumor shrinkage within days of starting treatment. Importantly, many patients reported improvement in their cancer-related symptoms, such as no longer requiring oxygen supplementation or decreased need for narcotics to control pain.

PD-L1 is a protein frequently overexpressed on the surface of cancer cells that acts as a disguise, allowing cancer cells to hide from the immune system. When MPDL3280A attaches to the PD-L1 protein, the cancer can no longer hide from the patient‟s immune system, allowing the body‟s T-cells to fight the cancer. MPDL3280A was specifically engineered for enhanced safety and efficacy compared to earlier PD-L1 or PD-1 targeted agents.

“We are impressed with the frequency and duration of the responses in these patients with very difficult-to-treat tumors. So far, almost none of the patients that have had tumor shrinkage have progressed,” said Roy S. Herbst, MD, PhD, Ensign professor of medicine at Yale Cancer Center and Chief of Medical Oncology at Smilow Cancer Hospital at Yale-New Haven. “This drug is part of an exciting new generation of drugs that unlock the power of the immune system to attack the cancer.” 

Efficacy was evaluated in 140 patients with locally advanced or metastatic solid tumors whose disease had progressed despite prior therapies. Tumor shrinkage was observed in patients with non-small cell lung cancer, melanoma, kidney cancer (renal cell carcinoma), colorectal cancer, and gastric cancer.

Overall, 29 out of 140 (21 percent) patients experienced significant tumor shrinkage and the highest number of therapy responses occurred in patients with lung cancer and melanoma. Therapy responses are still ongoing, with 26 out of 29 responders continuing to respond (time on study of responders 3-15+ months).

It is not yet clear how PD-L1 expression affects response to MPDL3280A. Using an investigational diagnostic test, researchers analyzed archived tumor tissue from 103 patients and found that tumor shrinkage occurred in 36 percent of patients with PD-L1 positive tumors and, surprisingly, also in 13 percent of patients with PD-L1 negative tumors. The diagnostic test for PD-L1 is still evolving, so currently a negative result on the PD-L1 test could simply mean that tumors have less PD-L1 than the test currently detects.

This study has been expanded to include a larger range of solid tumors and blood cancers, with more than 275 patients currently enrolled. While these early data are encouraging, a randomized trial is needed to confirm the findings. A number of phase II and phase III studies are already planned to confirm the drug‟s anti-cancer activity and further validate the utility of the PD-L1 diagnostic test. Researchers are also looking at ways it could be combined with other anti-cancer therapies to further boost responses over current standard treatments. 

ASCO Perspective: “The fact that this drug was active in such a variety of tumors suggests that PD-L1 is part of a universally or generally important immune mechanism. Over the next few years, drugs that target and help activate and direct the immune system will likely take on a growing role in patient care, and it‟s particularly exciting to see strong effects in patients whose cancer has progressed despite all other standard therapies,” said ASCO President-Elect Clifford A. Hudis, MD. 

This study was supported by Genentech, Inc.

Dr. Herbst is the recipient of a 1997 Conquer Cancer Foundation of ASCO Young Investigator Award and 1999 Career Development Award.

Relevant Links From Cancer.Net , the oncologist-approved cancer information website from the American Society of Clinical Oncology:  

Cancer.Net Guides to Cancer

Understanding Immunotherapy

Abstract #3000: A study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors.

Authors: Roy S. Herbst, Michael S. Gordon, Gregg Daniel Fine, Jeffrey Alan Sosman, Jean-Charles Soria, Omid Hamid, John D. Powderly II, Howard A. Burris III, Ahmad Mokatrin, Marcin Kowanetz, Maya Leabman, Maria Anderson, Daniel S. Chen, F. Stephen Hodi; Yale University, New Haven, CT; Pinnacle Oncology Hematology, Scottsdale, AZ; Genentech, Inc., South San Francisco, CA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Institut Gustave Roussy, Villejuif, France; The Angeles Clinic and Research Institute, Los Angeles, CA; Carolina BioOncology Institute, Huntersville, NC; Sarah Cannon Research Institute, Nashville, TN; Genentech Inc., South San Francisco, CA; Dana-Farber Cancer Institute, Boston, MA

Background: Tumor PD-L1 mediates cancer immune evasion. Therefore, inhibition of PD-L1 binding represents an attractive strategy to restore tumor-specific T-cell immunity. MPDL3280A, a human monoclonal antibody containing an engineered Fc-domain designed to optimize efficacy and safety, targets PD-L1, blocking PD-L1 from binding its receptors, including PD-1 and B7.1. Methods: A study was conducted with MPDL3280A administered IV q3w in pts with locally advanced or metastatic solid tumors, including 3+3 dose-escalation and expansion cohorts. ORR was assessed by RECIST v1.1 and includes u/cCR and u/cPR. Results: As of Jan 10, 2013, 171 pts were evaluable for safety. Administered doses include ≤1 (n=9), 3 (n=3), 10 (n=35), 15 (n=57) and 20 mg/kg (n=67). Pts in the dose-escalation cohorts did not experience DLTs. No MTD was identified. Pts had received MPDL3280A for a median duration of 127 days (range 1-330). 39% of pts reported G3/4 AEs, regardless of attribution. AEs of special interest included hepatitis, rash and colitis. No G3-5 pneumonitis was observed. MPDL3280A PK was linear at doses ≥1 mg/kg. 122 pts enrolled prior to Jul 1, 2012 were evaluable for efficacy. RECIST responses were observed in multiple tumor types including NSCLC, RCC, melanoma, CRC and gastric cancer. An ORR of 21% (25/122) was observed in nonselected solid tumors, including several pts who demonstrated tumor shrinkage within days of initiating treatment. Additional pts had delayed responses after apparent radiographic progression (not included in the ORR). Some responders demonstrated prolonged SD prior to RECIST responses. The 24-week PFS was 44%. Pts with PD-L1–positive tumors (from archival samples) showed an ORR of 39% (13/33) and a PD rate of 12% (4/33). In contrast, patients with PD-L1–negative tumors showed an ORR of 13% (8/61) and a PD rate of 59% (36/61). As of the cutoff date, all responses are ongoing or improving. Updated data will be presented. Conclusions: MPDL3280A was well tolerated, with no pneumonitis-related deaths. Durable responses were observed in a variety of tumors. PD-L1 tumor status appears to correlate with responses to MPDL3280A. PK supports q3w dosing at 15 mg/kg or fixed-dose equivalent.

Disclosures: Roy S. Herbst, MD, PhD, Research Funding from Genentech, Michael S. Gordon, MD, Consultant or Advisory Role with Genentech, Research Funding from Genentech, Gregg Daniel Fine, MD, Employment/Leadership Position with Genentech, Stock Ownership with Genentech/Roche, Jeffrey Alan Sosman, MD, Consultant or Advisory Role with Roche/Genentech, Honoraria from Roche/Genentech, Research Funding from Roche/Genentech, Jean-Charles Soria, Consultant or Advisory Role with Roche/Genentech, Honoraria from Roche/Genentech, Omid Hamid, MD, Consultant or Advisory Role with Genentech, Honoraria from Genentech, Research Funding from Genentech, John D. Powderly II, MD, Enployment/Leadership Position with BioCytics, Consultant or Advisory Role with Genentech/Roche, Stock Ownership with BioCytics, Honoraria from Genentech, Bristol-Myers Squibb, Research Funding from Celldex, Millennium, ImClone Systems, Genentech, Lilly, Bristol-Myers Squibb and Amgen, Ahmad Mokatrin, Employment/Leadership Position with Genentech, Stock Ownership with Genentech/Roche, Marcin Kowanetz, PhD, Employment/Leadership Position with Genentech, Stock Ownership with Genentech/Roche, Maya Leabman, Employment/Leadership Position with Genentech, Stock Ownership with Genentech/Roche, Maria Anderson, Employment/Leadership Position with Genentech/Roche, Stock Ownership with Genentech/Roche, Daniel S. Chen, M.D., Ph.D., Employment/Leadership Position with Genentech, Stock Ownership with Genentech, F. Stephen Hodi, MD, Consultant or Advisory Role with Genentech, Research Funding from Genente

 Phase I Trial Suggests Ipilimumab and PD-1 Drug Nivolumab May Be Better Together than Alone for Advanced Melanoma

Results from a phase I study show that combination therapy with ipilimumab (Yervoy) and the investigational antibody drug nivolumab led to lasting tumor shrinkage in approximately half of patients with aggressive, advanced melanoma. 

Ipilimumab is a standard treatment option for advanced melanoma in many countries. Nivolumab, used alone, has shown promising activity against melanoma and other cancers. Both nivolumab and ipilimumab are antibody drugs that target immune system “gatekeepers” or checkpoints (PD-1 and CTLA-4, respectively) on immune cells, effectively releasing the brakes on the immune system and boosting its ability to fight off cancer. This proof-of-principal study shows that concurrent use of two immune checkpoint antibodies offers a promising strategy for advanced melanoma therapy.

“The complete and near-complete response rates we‟re seeing are unprecedented for an immunotherapy in melanoma. We were particularly impressed that the drugs work together so well,” said Jedd D. Wolchok, MD, PhD, a medical oncologist at the Memorial Sloan-Kettering Cancer Center. “Melanoma researchers have been hopeful that combination regimens would increase the effectiveness of single-agent immunotherapies, and now we have confirmation that such an approach has significant potential.”

In this trial, patients with inoperable stage III and stage IV (metastatic) melanoma who had undergone up to three prior therapies were assigned to six different treatment arms. The current results are based on 37 patients in three completed treatment arms, in which patients received concurrent treatment with the two drugs.

In those three arms, tumor shrinkage rates were 21 percent, 47 percent, and 50 percent, with highest rates seen in patients treated with the highest dose of both drugs. The responses to therapy were rapid for an immunotherapy– three out of four patients who responded to the concurrent treatment experienced tumor reduction within the first three months, which is faster than with single-agent ipilimumab. Thirty percent of patients experienced significant tumor shrinkage of more than 80 percent.

Two of the remaining three arms enrolled patients who had undergone prior ipilimumab treatment. Those patients received only nivolumab on this study. While the data are still preliminary, it appears that even patients who initially had little benefit from ipilimumab had significant tumor shrinkage after subsequent treatment with nivolumab.

Side effects have been manageable in the trial and did not impact the positive therapeutic activity for the majority of the patients in this analysis. A randomized phase III trial of the nivolumab/ipilimumab combination as first-line therapy for patients with advanced melanoma is scheduled to begin in June 2013.

ASCO Perspective: “The further exploration of immunotherapy as stand-alone therapy without chemotherapy for a devastating disease such as advanced melanoma is a tremendous advance. We are identifying therapies that appear better together than alone, and look promising for more than just a small subset of patients. The extensive tumor shrinkage that was observed in this study is exactly the type of benefit patients and doctors have been hoping for,” said ASCO President Sandra M. Swain, MD, FACP.

This research was supported by Bristol-Myers Squibb.

Relevant Links From Cancer.Net , the oncologist-approved cancer information website from the American Society of Clinical Oncology:  

Guide to Melanoma

Understanding Immunotherapy

Abstract #9012: Safety and clinical activity of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in combination with ipilimumab in patients (pts) with advanced melanoma (MEL).

Authors: Jedd D. Wolchok, Harriet M. Kluger, Margaret K. Callahan, Michael Andrew Postow, Ruth Ann Roman, Neil Howard Segal, Naiyer A. Rizvi, Alexander M. Lesokhin, Kathleen Reed, Matthew M. Burke, Anne Caldwell, Stephanie Anne Kronenberg, Blessing Agunwamba, William Feely, Quan Hong, Christine E. Horak, Alan J. Korman, Jon M. Wigginton, Ashok Kumar Gupta, Mario Sznol; Memorial Sloan-Kettering Cancer Center, New York, NY; Yale School of Medicine; Yale Cancer Center, New Haven, CT; Memorial-Sloan Kettering Cancer Center, New York, NY; Bristol-Myers Squibb, Princeton, NJ; Bristol-Myers Squibb, Redwood City, CA

Background: CTLA-4 and PD-1 are critical immune checkpoint receptors. In MEL pts, ipilimumab (anti-CTLA-4) prolonged survival in two phase III trials, and nivolumab (anti-PD-1) produced an objective response rate (ORR) of 31% (n=106) in a phase I trial. PD-1 is induced by CTLA-4 blockade, and combined blockade of CTLA-4/PD-1 showed enhanced antitumor activity in murine models. Thus, we initiated the first phase 1 study to evaluate nivolumab/ipilimumab combination therapy. Methods: MEL pts with ≤3 prior therapies received IV nivolumab and ipilimumab concurrently, q3 wk × 4 doses, followed by nivolumab alone q3 wk × 4 (Table). At wk 24, combined treatment was continued q12 wk × 8 in pts with disease control and no DLT. In two sequenced-regimen cohorts, pts with prior standard ipilimumab therapy were treated with nivolumab (q2 wk × 48). Results: As of Dec. 6, 2012, 69 pts were treated. We report efficacy data on 37 pts with concurrent therapy in completed cohorts 1-3 (Table); ORR was 38% (95% CI: 23-55). In cohort 2 (MTD), ORR was 47% and 41% of pts had ≥80% tumor reduction at 12 wk with some pts showing rapid responses, prompt symptom resolution, and durable CRs. Related adverse events (rAEs) for concurrent therapy were similar in nature with some higher in frequency than those typically seen for the monotherapies and were generally manageable using immunosuppressisants. Cohort 3 exceeded the MTD (DLT: gr 3-4 ↑ lipase). At the MTD, gr 3-4 rAEs occurred in 59% of pts and included uveitis/choroiditis, colitis, and reversible lab abnormalities. Conclusions: Nivolumab and ipilimumab can be combined with a manageable safety profile. Clinical activity for concurrent therapy appears to exceed that of published monotherapy data, with rapid and deep tumor responses (≥80% tumor reduction at 12 wk) in 30% (11/37) of pts. A phase III trial is planned to compare concurrent combination dosing with each monotherapy.

Disclosures: Jedd D. Wolchok, MD, PhD, Consultant or Advisory Role with Bristol-Meyers Squibb, Research Funding from Bristol-Meyers Squibb, Margaret K. Callahan, MD, PhD, Research Funding from Bristol-Meyers Squibb, Michael Andrew Postow, MD, Consultant or Advisory Role with Brisol-Meyers Squibb, Ruth Ann Gordon, RN, BSN, OCN, Other Renumeration from Brisol-Meyers Squibb, Alexander M. Lesokhin, MD, Research Funding from Bristol-Meyers Squibb, Matthew M. Burke, Consultant or Advisory Role with Bristol-Meyers Squibb, Honoraria from Bristol-Meyers Squibb, William Feely, Employment/Leadership Position with Bristol-Meyers Squibb, Quan Hong, Ph.D, Employment/Leadership Position with Bristol-Meyers Squibb, Stock Ownership with Bristol-Meyers Squibb, Christine E. Horak, PhD, Employment/Leadership Position with Bristol-Meyers Squibb, Stock Ownership with Bristol-Meyers Squibb, Alan J. Korman, PhD, Employment/Leadership Position with Bristol-Meyers Squibb, Stock Ownership with Bristol-Meyers Squibb, Jon M. Wigginton, MD, Employment/Leadership Position with Bristol-Meyers Squibb, Stock Ownership with Bristol-Meyers Squibb, Ashok Kumar Gupta, MD, PhD, MBBS, Employment/Leadership Position with Bristol-Meyers Squibb, Stock Ownership with Bristol-Meyers Squibb

Standard-Dose Radiation Is Superior to High-Dose Radiation for Patients with Locally Advanced Stage III NSCLC Undergoing Chemotherapy (Summary includes updated data not in the abstract)

 A phase III trial in patients with stage III non-small cell lung cancer (NSCLC) concludes that standard dose (SD) radiotherapy (60 Gy) is safer and more effective than high-dose (HD) radiotherapy (74 Gy), extending survival by nine months and causing fewer treatment related deaths. While 60 Gy is already standard, many doctors use higher doses expecting better outcomes. These findings should put an end to higher-dose treatment, given better outcomes in the standard dose arm. 

Radiation therapy is used to control the growth of the primary tumor and cancer spread to the nearby (regional) lymph nodes. Although HD therapy in this patient population appeared promising in earlier phase I and phase II clinical trials, this study clearly shows that it is associated with dramatically shorter survival.

“We expected at the outset that high-dose radiation therapy would lead to better outcomes. We were surprised, though also pleased, to discover that less intense treatment led to better control of cancer progression and spread, and even improved overall survival,” said lead author Jeffrey D. Bradley, MD, a professor of radiation oncology at the Washington University School of Medicine in St. Louis, Mo. “The biological reasons for failure of the high dose with respect to overall survival and local-regional control are not readily apparent.” 

In the study, 464 patients were randomly assigned to treatment with SD or HD radiation therapy along with standard chemotherapy (paclitaxel and carboplatin). In each treatment arm, the patients were also randomly assigned to receive cetuximab (Erbitux) or no additional therapy. Data on the effects of cetuximab on survival will be reported at a later date. The HD arm was closed after an interim analysis showed it was not superior to the SD arm.

The median survival for patients who received SD radiation therapy was much longer compared to that in patients who received HD radiation therapy (28.7 months vs. 19.5 months) and the estimated 18-month overall survival rates were also higher for the SD arm (66.9 percent vs. 53.9 percent). Cancer recurrence rates at 18 months were higher in the HD group of patients compared with the SD group (local recurrence rates were 34.3 percent vs. 25.1 percent, and distant recurrence rates were 44 percent vs. 35.3 percent). While the primary cause of death for most patients was lung cancer, there were a notably higher number of treatment-related deaths in the HD arm (10), compared to the SD arm (2).

ASCO Perspective: “This is a critical study in the field of radiation oncology. After a decade of research, we can finally close the chapter on high-dose vs. standard-dose therapy debate in lung cancer therapy, using evidence-based data to improve care for our patients,” said ASCO President Sandra M. Swain, MD, FACP. 

This research was supported by the National Cancer Institute and Eli Lilly and Company. 

Relevant Links From Cancer.Net , the oncologist-approved cancer information website from the American Society of Clinical Oncology:  

Guide to Lung Cancer

Understanding Radiation Therapy

What to Know: ASCO‟s Guideline on Adjuvant Treatment for Lung Cancer

Abstract #7501: A randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) conformal chemoradiotherapy with or without cetuximab for stage III non-small cell lung cancer: Results on radiation dose in RTOG 0617.

Authors: Jeffrey D Bradley, Rebecca Paulus, Ritsuko Komaki, Gregory A. Masters, Kenneth Forster, Steven E. Schild, Jeffrey Bogart, Yolanda I. Garces, Samir Narayan, Vivek Kavadi, Lucien Alexander Nedzi, Jeff M. Michalski, Douglas Johnson, Robert Malcolm MacRae, Walter John Curran, Hak Choy, Radiation Therapy Oncology Group; Washington University School of Medicine in St. Louis, St. Louis, MO; Radiation Therapy Oncology Group, Statistical Center, Philadelphia, PA; The University of Texas MD Anderson Cancer Center, Houston, TX; Helen F. Graham Cancer Center, Christiana Care, Newark, DE; Moffitt Cancer Center, Tampa, FL; Mayo Clinic, Scottsdale, AZ; SUNY Upstate Medical University, Syracuse, NY; Mayo Clinic, Rochester, MN; St Joseph Mercy Hosp, Ann Arbor, MI; Texas Oncology, Sugarland, TX; The University of Texas Southwestern Medical Center, Dallas, TX; Florida Radiation Oncology Group, Jacksonville, FL; The Ottawa Hospital, Ottawa, ON; Emory University, Atlanta, GA

Background: The first objective of RTOG 0617 was to compare the overall survival(OS) of patients(pts) treated with standard-dose(SD)(60Gy) versus high-dose(HD)(74Gy) radiotherapy with concurrent chemotherapy(CT). Methods: This phase III Intergroup trial randomized 464 pts with Stage III NSCLC to the SD(60Gy) vs. HD(74Gy) arms prior to closure of the HD arm. Concurrent CT included weekly paclitaxel(45 mg/m2) and carboplatin(AUC=2). Pts randomized to cetuximab received a 400 mg/m2 loading dose on Day 1 followed by weekly doses of 250 mg/m2. All pts were to receive consolidation CT. We are reporting the final results on radiation dose. Results: 464 pts were accrued prior to closure of the HD arm in 6/11, of which 419 were eligible for analysis. Median follow up was 17.2 months. There were 2 and 10 grade 5 treatment-related adverse events(AEs) on the SD and HD arms, respectively. Grade 3+AEs were 74.2% and 78.2% on SD and HD arms, respectively (p=0.34). The median survival times and 18-month OS rates for the SD and HD arms were 28.7 vs 19.5 months, and 66.9% vs 53.9% respectively (p=0.0007). The primary cause of death was lung cancer (72.2% vs 73.5%)(p=0.84). Local failure rates at 18 months were 25.1% vs 34.3% for SD and HD patients, respectively(p=0.03). Local-regional and distant failures at 18 months were 35.3% vs 44%(p=0.04) and 42.4% vs 47.8%(p=0.16) for SD and HD arms, respectively. Factors predictive of less favorable OS on multivariate analysis were higher radiation dose, higher esophagitis/dysphagia grade, greater gross tumor volume, and heart volume >5 Gy. Conclusions: In this setting of chemoradiation for locally-advanced Stage III NSCLC, 60 Gy is superior to 74 Gy in terms of OS and local-regional control. The effect of the anti-EGFR antibody (cetuximab) awaits further follow up. This project was supported by RTOG grant U10 CA21661, CCOP grant U10 CA37422, and ATC U24 CA 81647 from the National Cancer Institute (NCI) and Eli Lilly and Company.

Disclosures: Jeff M. Michalski, MD, Research Funding from NCI 

 Surveillance Following Surgery Is Sufficient for Men with Stage I Seminoma 

A long-term study of men with stage I seminoma, a common form of testicular cancer, suggests that surveillance for cancer recurrence, rather than additional chemotherapy or radiation therapy, is sufficient for the vast majority of men who have undergone successful surgery for their cancer. Researchers found that 99.6 percent of patients who underwent surveillance only were alive 10 years after their initial diagnosis.

Surveillance entails five years of scheduled physical exams, chest X-ray exams, CT scans and blood tests. In Denmark, where this study was conducted, surveillance is the follow-up strategy of choice. In the United States, about 50 percent of patients receive surveillance alone following surgery, while the remainder undergo either radiotherapy or chemotherapy (carboplatin). However, there has been a recent shift towards surveillance in the United States – a trend that will likely accelerate with these new data. Avoiding additional treatments spares patients of associated harmful side effects, such as a potential risk of secondary cancers, including gastrointestinal cancers and leukemia, following radiotherapy.

“To our knowledge, this study is the largest to address this issue in patients with stage I seminoma, and with the longest follow-up. Now we have solid proof that surveillance is safe and appropriate for most patients with this particular cancer,” said Mette Saksø Mortensen, MD, a PhD student at the Department of oncology at the Copenhagen University Hospital in Copenhagen, Denmark. “We also characterized key prognostic factors for relapse, which can help us identify „high-risk‟ patients who may need adjuvant therapy instead of surveillance. However, in general, seminoma stage I patients can safely be followed on a surveillance program.”

Using a nationwide clinical database, researchers identified 1,822 patients with stage I seminoma followed on a five year surveillance program in Denmark. By linking the patient files with national registries they were able to follow the patients for a median period of 15.4 years. All patients had initial surgery to treat their primary cancer. Overall, 355 of 1,822 patients (19.5 percent) experienced a relapse, which was treated with radiotherapy (216 patients), chemotherapy (136 patients) or surgery (3 patients). The 10-year cancer-specific survival was 99.6 percent. This rate means that for every 1,000 men followed on a surveillance program, only four die within 10 years.

Researchers found that tumor size larger than 1.5 inches, spread to blood or lymphatic vessels, and elevated levels of a blood marker called human chorionic gonadotropin increased the risk of relapse. These factors had been associated with high-risk patients in prior, smaller studies.

Seminoma accounts for about half of testicular cancer cases. Testicular cancer is rare in the general population, but it is the most common solid tumor among young men. About 4,000 new cases of stage I seminoma will be diagnosed in the United States this year. The typical initial treatment for the disease is orchiectomy, or surgical removal of the affected testicle and the spermatic cord.

ASCO Perspective: “This important study is one of several recent reminders that sometimes "less is more‟ in patient care. Opting for surveillance spares patients, most of whom are young men, from the harmful side effects of chemotherapy and radiation without diminishing their chances for a long and healthy life,” said ASCO President-Elect Clifford A. Hudis, MD.

This research was supported in part by The Danish Cancer Society, The Danish Cancer Research Foundation and the Preben and Anna Simonsen Foundation.

Relevant Links From Cancer.Net , the oncologist-approved cancer information website from the America Society of Clinical Oncology:  

Guide to Testicular Cancer

What to Know: ASCO‟s Guideline on Tumor Markers for Testicular Cancer and Extragonadal Germ Cell Tumors in Teenage Boys and Men

Abstract #4502: A nationwide cohort study of surveillance for stage I seminoma.

Authors: Mette Saksoe Mortensen, Maria Gry Gundgaard, Jakob Lauritsen, Mads Agerbaek, Niels Vilstrup Holm, Hans von der Maase, Gedske Daugaard; Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Survivorship, Danish Cancer Society, Copenhagen, Denmark; Aarhus University Hospital, Aarhus, Denmark; Odense University Hospital, Odense, Denmark

Background: The standard treatment for stage I seminoma remains a topic for discussion. Survival rates are excellent irrespective of treatment modality (radiotherapy, carboplatin or surveillance). However, late effects might differ between treatment options. Only smaller surveillance studies with limited follow-up have previously been published. We present data from a large nationwide cohort study on surveillance in stage I seminoma patients. Methods: A nationwide and population based clinical database covering germ cell cancer patients diagnosed 1984-2007 was constructed. The database included 4,683 cases. All stage I seminoma patients followed by surveillance were identified. Possible prognostic factors for relapse were collected from patient files and pathology reports. By merging our data with the national patient registry we were able to collect data on late relapses, vital status and cause of death on all patients up to December 2012. Results: 1,822 patients with stage I seminoma were followed on a surveillance program. The median follow-up time was 15.4 years. Ten year cancer specific survival (CSS) was 99.6%. A total of 355 (19.5%) patients had a relapse after a median time of 13.7 months (range 1.2-173.7 months). Within 2-5 years after orchiectomy, 72 patients (4.0 %) had a relapse and 26 patients (1.4 %) had a relapse more than 5 years after orchiectomy. Invasion of blood or lymphatic vessels, tumor size > 4 cm and serum human chorionic gonadotropin > 200 IU/L were all predictive factors for relapse in both univariate and multivariate analyses (p<0.01). Invasion of rete testis was significant in the univariate analysis but not in the multivariate analyses (p=0.53). Conclusions: We present the largest cohort ever published of stage I seminoma patients followed on a surveillance program. The prognosis was excellent with a 10 year CSS of 99.6%. Prognostic factors for relapse were identified. The relapse rate after 5-years of follow-up was 1.4%. Surveillance should be the preferred option of management in stage I seminoma patients. Several international guidelines are now in agreement with this statement.

Disclosures: Nothing to disclose 

Routine Surveillance Imaging Scans Add Little to Detection of Relapse in Patients with Diffuse Large B-Cell Lymphoma

 A large study reports that the vast majority of diffuse large B cell lymphoma (DLBCL) relapses are detected based on symptoms, abnormal blood tests or abnormal findings on physical exam, suggesting that CT scans, which are currently a routine part of follow-up, may be unnecessary. Researchers found that just 1.5 percent of patients in remission had a relapse that was detected solely through a scheduled imaging scan. These findings will help physicians develop guidelines for following patients in remission for DLBCL and spare patients from the excess radiation exposure and costs associated with unnecessary CT scans. 

Current surveillance guidelines for DLBCL recommend CT scans no more than every six months for two years after the completion of treatment, and as clinically indicated thereafter. Generally, patients also receive physical exams and blood tests during follow-up. However, optimal surveillance strategies have been unclear.

“Scans expose patients to radiation and that theoretically increases the risk of a second cancer. Surveillance scans can also increase patient anxiety and lead to biopsies that may not be necessary,” said lead study author Carrie A. Thompson, MD, a hematologist at Mayo Clinic, Rochester, Minn. “While our study shows that the majority of relapses are detected by patient symptoms, the decision of whether to do surveillance scans and how often should be tailored to each individual patient.”

Researchers assessed post-treatment outcomes (relapse, re-treatment and death) in 644 patients enrolled in a prospective, multi-institutional cohort of patients with newly diagnosed DLBCL. All patients had received initial treatment with standard anthracycline based immune-chemotherapy.

During a median follow-up period of 59 months, 109 out of 537 patients (20 percent) who entered post-treatment follow-up experienced a relapse. Overall, at the time of relapse 68 percent of patients had symptoms, 42 percent had an abnormal finding on physical exam, and 55 percent had abnormalities in blood tests. Planned surveillance scans detected relapses in only 8 out of 537 (1.5 percent) of patients before clinical signs appeared.

Given that so many relapses are accompanied by symptoms, patients should be vigilant about reporting symptoms between scheduled visits, Dr. Thompson said. Some signs of a possible relapse in DLBCL include enlarged lymph nodes, night sweats, unexplained fever, and unintentional weight loss.

DLBCL is the most common form of lymphoma, accounting for 30 percent of non-Hodgkin lymphoma cases. The disease is aggressive but potentially curable with a combination of chemotherapy and targeted immunotherapy (rituximab). However, up to a third of patients experience a relapse after achieving remission. Relapsed DLBCL is often treated with stem cell transplantation and high-dose chemotherapy.

ASCO Perspective: “The oncology community has already begun to reevaluate the utility of advanced imaging scans and some aspects of surveillance in the routine follow-up of patients with certain cancers. This study is one case in which the benefits of such scans do not appear to outweigh their potential burdens on patients, in terms of anxiety, physical risks or financial costs. Patients should discuss with their doctors how these findings pertain to their care,” said ASCO President-Elect Clifford A. Hudis, MD.

This research was supported in part by the National Cancer Institute and Mayo Clinic Center for the Science of Health Care Delivery.

Relevant Links From Cancer.Net , the oncologist-approved cancer information website from the American Society of Clinical Oncology:  

Guide to Non-Hodgkin Lymphoma

Computed Tomography (CT) Scan – What to Expect

CT Scans and Cancer Risk

Abstract #8504: Utility of post-therapy surveillance scans in DLBCL.

Authors: Carrie A. Thompson, Matthew J. Maurer, Herve Ghesquieres, William R Macon, Thomas Matthew Habermann, Thomas E. Witzig, James Robert Cerhan, Brian K. Link; Mayo Clinic, Rochester, MN; Centre Léon Bérard, Lyon, France; University of Iowa Hospitals and Clinics, Iowa City, IA

Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma. The optimal follow-up strategy for patients (pts) in remission is not clear. The goal of this study is to determine the utility of surveillance scans in a large, prospective, multi-institutional cohort of DLBCL pts. Methods: Patients were enrolled in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER), a prospective cohort of newly diagnosed lymphoma pts. All pts were followed for events including relapse, re-treatment, and death with events verified by medical records. Patients eligible for this study had biopsy proven DLBCL and were treated with anthracycline based immunochemotherapy (IC). Initial and post-treatment management was per treating physician. Medical records were re-reviewed in pts with events for clinical details at relapse and relationship to planned follow-up visits and surveillance scans. Results: 644 pts with DLBCL treated with IC were enrolled in MER from 2002-2009. Median age was 63 years (range 18-92), 54% were men, and median f/u was 59 months (range 8-116). 537 pts entered post-treatment observation; 109 (20%) of the 537 pts relapsed and 41 died from other causes. 42% of relapses were in the first 12 months following diagnosis, 27% between 12-24 months, and 31% >24 months. In the 109 who relapsed, 62% of pts (62/100, 9 unknown) presented to their physician earlier than a planned follow-up visit due to symptoms. At the time of relapse, 68% were symptomatic, 42% of pts had abnormal physical exam, and 55% had elevated LDH; 87% of pts had ≥1 of these features. Of the 38 pts with relapse detected at a planned visit, 26 had clinical features of relapse and 12 pts had relapse detected solely by planned surveillance scan; 4 pts had relapse of low-grade or other subtype and 8 had DLBCL relapse (4 of whom had equivocal/positive PET at the end of IC). Thus, surveillance scanning detected DLBCL relapse prior to clinical manifestations in only 8/537 pts (1.5%) observed post DLBCL therapy. Conclusions: The vast majority of DLBCL relapses occur outside of planned follow-up visits and are accompanied by symptoms, physical exam, or laboratory abnormalities. Routine surveillance scans post-therapy add little to detection of DLBCL relapse.

Disclosures: Nothing to disclose 

New Drug Targeting PI3K-delta Shows Strong Activity in Early Trial for High-Risk Chronic Lymphocytic Leukemia

 Results from a phase I study of a new oral targeted drug, idelalisib (GS-1101), show the agent has potential as a therapy for relapsed or treatment-resistant chronic lymphocytic leukemia (CLL). The drug produced rapid and long-lasting tumor shrinkage in half of the patients treated with single-agent therapy, stalling disease progression for 17 months, on average. The activity of the drug is noteworthy, given that the patients had already undergone an average of five prior therapies. 

CLL, which is typically diagnosed through a routine blood test, is a slow-growing cancer and many patients do not require treatment until they start having symptoms. The vast majority of patients with CLL experience a relapse at some point after initial treatment with chemoimmunotherapy. And about 20 percent of patients have so-called refractory disease, meaning that they either relapse quickly (within six months) or do not respond to initial treatment at all. Both of those categories of patients are in need of better treatments, as the currently approved options (immunotherapy and chemotherapy) have limited success.

Idelalisib is the first drug that selectively blocks PI3K-delta, a subtype of PI3K proteins that is overactive specifically in B cell lymphoma, and is critical for tumor growth. While other PI3K inhibitors have been explored, this is the first study of a PI3K inhibitor – including a PI3K-delta inhibitor – specifically in patients with CLL.

“We are reaching a point in CLL where we have multiple agents in development that are very effective. Drugs like idelalisib are probably going to change the landscape of the disease in the next few years,” said lead study author Jennifer Brown, MD, PhD, an assistant professor of medicine at Dana-Farber Cancer Institute. “While this research is still early and ongoing, we hope this drug, along with others like it, will lead to prolonged survival and eventually help turn CLL into a condition that is treated like high blood pressure, where a patient can take a couple of pills every day. In the shorter term, these drugs may also provide an alternative to chemotherapy in elderly patients who tend not to tolerate chemotherapy well.” 

This trial included 54 patients with refractory or relapsed CLL who received idelalisib. The patients‟ cancer had worsened despite having received a median of five prior therapies. The average duration of idelalisib treatment was nine months. Tumor reduction with clinical benefit was rapid for this disease, generally occurring in the first two months after beginning therapy, and was observed in about two-thirds of patients. On average, the drug delayed disease progression by 17 months, which is better than typically expected for a sixth-line therapy, which might usually have benefit for six to 12 months. Many patients experienced a decrease in disease symptoms, such as fatigue. Patients who benefited from the drug were offered the opportunity to continue treatment on an extension study.

The researchers reported that side effects were manageable; only seven percent of patients discontinued treatment due to treatment-related effects.

ASCO Perspective: “This study illustrates how our growing understanding of tumor biology enables development of highly active and highly promising targeted drugs. It also offers a glimpse at the possibility of a new, chemotherapy-free alternative for chronic blood cancers, where active treatment is simple, effective and may even improve a patient‟s overall quality of life,” said ASCO President Sandra M. Swain, MD, FACP.

This research was supported by Gilead Sciences.

Relevant Links From Cancer.Net , the oncologist-approved cancer information website from the American Society of Clinical Oncology:  

Guide to Chronic Lymphocytic Leukemia

Understanding Targeted Treatments

Abstract #7003: Final results of a phase I study of idelalisib (GS-1101) a selective inhibitor of PI3Kδ, in patients with relapsed or refractory CLL.

Authors: Jennifer R. Brown, Richard R. Furman, Ian Flinn, Steven E. Coutre, Nina D. Wagner-Johnston, Brad S. Kahl, Stephen Edward Forbes Spurgeon, Don M. Benson Jr., Sissy Peterman, David Michael Johnson, Daniel Li, Roger D. Dansey, Thomas Michael Jahn, John C. Byrd; Dana-Farber Cancer Institute, Boston, MA; Weill Cornell Medical College, New York, NY; Sarah Cannon Research Institute, Nashville, TN; Stanford Cancer Institute, Stanford, CA; Washington University School of Medicine in St. Louis, St. Louis, MO; University of Wisconsin Carbone Cancer Center, Madison, WI; Oregon Health & Science University, Portland, OR; The Ohio State University, Columbus, OH; Gilead Sciences, Inc., Seattle, WA

Background: Signals through PI3K-delta regulate activation, proliferation and survival of B cells, critically influence homing and retention of B cells in lymphoid tissues, and are hyperactive in many B-cell malignancies. Idelalisib (GS-1101) is a first-in-class, selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and inhibits homing and retention of malignant B cells. Methods: Pts with relapsed/refractory CLL were treated continuously with single-agent oral idelalisib from 50-350 mg/dose (QD or BID). Response evaluated by investigators per Hallek (2008) and Cheson (2012). Results: 54 pts (9F/45M) median (range) age 63 (37-82) years enrolled with: bulky lymphadenopathy (80%), refractory disease (70%), extensive prior therapies (median: 5, range: 2-14), unmutated IgHV (91%), del17p and/or TP53 mutation (24%), del11q (28%), NOTCH1 mutation (17%). The median (range) exposure was 9 (0-41+) months. 25 (46%) pts completed the primary study, 23 (43%) enrolled into an extension study. ORR was 30/54 (56%, 2 CR, 28 PR). Of the 28 PR, 22 met Hallek (2008) and 6 met PR with lymphocytosis Cheson (2012). 44/54 (81%) showed a lymph node response (≥50% reduction in the nodal SPD). 21/54 were SD and 3/54 NE. The median (range) time to first response was 1.9 (0.9-12.9) months. Median PFS was 17 months and median DOR was 18 months. Idelalisib treatment resulted in resolution of splenomegaly (14/20, 70%) and normalization of cytopenias: anemia (17/25, 68%); thrombocytopenia (27/34 79%), neutropenia (15/15, 100%). Most common AEs independent of causality (any Grade/≥Gr 3) included fatigue (31%/2%), diarrhea (30%/6%), pyrexia (30%/4%), rash (22%/0%), upper respiratory tract infection (22%/0%), pneumonia (20%/19%). 2% of pts had ≥Gr 3 ALT/AST elevation. 15% of pts discontinued due to AEs, 7% potentially treatment-related. There were no dose-limiting toxicities. Conclusions: Idelalisib shows substantial clinical activity and a favorable safety profile in heavily pretreated, refractory and high-risk pts with CLL. Phase 3 trials with idelalisib in combination with rituximab or bendamustine/rituximab are ongoing (NCT01539512, NCT01569295).

Disclosures: Ian Flinn, MD, PhD, Research Funding from Gilead Sciences. 

ATTRIBUTION TO THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING IS REQUESTED IN ALL NEWS COVERAGE. 

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Click here to view the disclosures for the 2013 ASCO Annual Meeting News Planning Team. 

 About ASCO 

The American Society of Clinical Oncology (ASCO) is the world‟s leading professional organization representing physicians who care for people with cancer. With more than 30,000 members, ASCO is committed to improving cancer care through scientific meetings, educational programs and peer-reviewed journals. ASCO is supported by its affiliate organization, the Conquer Cancer Foundation, which funds ground-breaking research and programs that make a tangible difference in the lives of people with cancer. For ASCO information and resources, visit www.asco.org . Patient-oriented cancer information is available at www.cancer.net. 

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