San Francisco, CA USA (UroToday.com) Kidney cancer has always been thought to be an immunogenic malignancy. Much fanfare has followed the discovery and application of checkpoint inhibition via PD-1, PD-L1 and CTLA4 in a variety of genitourinary malignancies. One would be remiss, however, not to recall that interleukin-2 (IL-2) was the original immunotherapy in kidney cancer and remains the only therapy to achieve long term durable complete response (~5%). In this session Dr. Pal explored the optimal strategy for treatment of patients with metastatic clear cell renal cell carcinoma (mccRCC).
He began by highlighting the SELECT trial (McDermott et al., CCR 2015). This trial enrolled patients with mccRCC and treated them with high dose IL-2 for 5 days x 2 with a 9-day rest period in between doses. This was followed by 9-week break. Three total cycles were given. The primary objective was to determine whether patients with “good” pathologic features had a significantly better overall response rate (ORR) to high-dose IL-2 than prior unselected controls. Of 120 patients enrolled,70% were intermediate risk and 11% were poor risk. ORR was not significantly better with clinical stratification, however, the investigators did demonstrate positive association between PD-L1 expression and ORR.
Given this, Dr. Pal hypothesized that biases in delivering IL-2 may result from three areas: selection bias, resource bias, experience bias. Because of this administration of IL-2 appears to be confined to specialized centers. He queried an international panel of thought leaders in this space and the following results were obtained. When asked whether they used HD IL-2 in your practice, 67% responded yes and 33% no. The “yes responders used young age, ccRCC histology, good performance status, and few comorbidities as predictors for IL-2 use. There was, however, no consensus on the ideal patient and no biomarkers to help in identifying ideal candidates. For the ideal patient (young, healthy, lung only metastases), only 36% responded that they would use IL-2, while 64% recommended a clinical trial.
Dr. Pal mentioned many trials. The general theme was that combinations, their timing in the disease process, and the order of agent use is the major focus of ongoing clinical trials. Many past trials have demonstrated exceptional survival in a minority of patients at the right side of the so-called “long tail.” He implored us to find out who these exceptional individual patients are and suggested trial embedded biomarkers as a means to achieve this goal.
Presented By:
Dr. Sumanta K. Pal, MD
City of Hope
Reported By:
Benjamin T. Ristau, MD, at the 2016 Genitourinary Cancers Symposium - January 7 - 9, 2016 – San Francisco, CA
Fox Chase Cancer Center, Philadelphia, PA