(UroToday.com) The 2022 ASCO annual meeting featured a session on kidney and bladder cancer, including a presentation by Dr. Ciara Conduit discussing the final report of UNISoN (ANSUP 1602) testing nivolumab followed by ipilimumab + nivolumab in advanced non-clear cell renal cell carcinoma (RCC). Immune checkpoint immunotherapy is active against many cancers. Many people are failed by PD1 inhibition alone, but not all patients benefit, nor require combination immune checkpoint immunotherapy treatment. UNISoN (NCT03177239) previously reported outcomes in people with non-clear cell RCC receiving nivolumab monotherapy, and nivolumab + ipilimumab in those whose cancers progressed after nivolumab alone. At the 2022 ASCO meeting, Dr. Conduit and colleagues presented the final planned report of UNISoN.
Participants with advanced non-clear cell RCC with good performance status (ECOG 0/1) received nivolumab 240mg every 2 weeks alone (Part 1). Those with cancers refractory to nivolumab at 3 months were offered a combination of ipilimumab (1 mg/kg) + nivolumab (3 mg/kg) every 3 weeks for up to 4 doses, followed by nivolumab 240 mg every 2 weeks for a maximum total of 12 months of nivolumab (Part 2). UNISoN was powered to identify a clinically-relevant objective tumor response rate of 30% (assuming 15% was not relevant) among people receiving nivolumab + ipilimumab in Part 2. The trial schema for UNISoN is as follows:
There were 83 patients with a representative spectrum of non-clear cell RCC histologies were enrolled and received nivolumab. Amongst the total population enrolled to UNISoN Part 1/2, median OS was 24 (16-28) months and 12-month OS was 65% (54%-74%):
Among those patients proceeding to Part 2, the median OS was 10 (6-17) months:
Overall, 17% (10%-27%; 14/83) and 10% (3%-23%; 4/41) of patients experienced a response from nivolumab alone or nivolumab + ipilimumab, respectively. The Waterfall plot of best overall response by histologic subtype in Part 2 is as follows:
Overall in Part 2, the median time on treatment was 2.1 (95% CI 1.8, 2.8) months, the median number of cycles was 3, and the median follow-up at final analysis was 22 (IQR 16-30) months. In this population, the median PFS was 2.6 (IQR 2.2-3.8) months and 12m PFS was 11% (4%-23%):
Additionally, 13% (7%-22%) of patients were free of progression or death at 24 months. The primary endpoint was not met as only 80% of patients failed by nivolumab were assessable for response in Part 2. Overall tumor responses from nivolumab alone or nivolumab + ipilimumab were more common in patients with papillary histology, whereas patients with chromophobe histology had poor outcomes. No late toxicity safety signals were observed.
Dr. Conduit concluded her presentation by discussing the final report of UNISoN testing nivolumab followed by ipilimumab + nivolumab in advanced non-clear cell RCC with the following take-home messages:
- Some patients with non-clear cell RCC benefit from nivolumab alone, or addition of ipilimumab when disease is inadequately controlled by nivolumab alone, however most patients have limited benefit from immune checkpoint immunotherapy
- More effective therapeutic options are needed for the majority of people with rare variant renal cell carcinomas
- Novel markers of response are required to more rapidly predict patients who will progress on nivolumab
- Translational research to identify predictive biomarkers of response is ongoing
Presented by: Ciara Conduit, MD, Australian & New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, Camperdown, Australia
Co-Authors: Ganessan Kichenadasse, Carole A. Harris, Howard Gurney, Tom Ferguson, Francis Parnis, Jeffrey C. Goh, Michelle Frances Morris, Craig Underhill, David William Pook, Ian D. Davis, Felicia Roncolato, Michelle L. Harrison, Stephen Begbie, Anthony M. Joshua, Emma Link, Elizabeth J. Hovey, Craig Gedye
Affiliations: Southern Oncology Clinical Research Unit, Bedford Park, SA, Australia, St. George Hospital Cancer Care Center, Kingsford, NSW, Australia, Macquarie University, Sydney, Australia, Royal Perth Hospital, Perth, Australia, Ashford Cancer Center, Adelaide, Australia, Department of Oncology, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia, Sunshine Coast University Private Hospital, Birtinya, Australia, Border Medical Oncology Research Unit, Albury Wodonga Regional Cancer Centre & Rural Medical School, Albury Campus, University of New South Wales, Albury-Wodonga, NSW, Australia, Monash Health, Melbourne, VIC, Australia, Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia, Macarthur Cancer Therapy Center, Sydney, Australia, Royal Prince Alfred Hospital, Hunters Hill, NSW, Australia, Port Macquarie Base Hospital, Port Macquarie, Australia, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada, Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Australia, Prince of Wales Hospital, Sydney, Australia, Calvary Mater Newcastle, Waratah, NSW, Australia
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.