Continuing Nivolumab After Progression May Reduce mRCC Tumour Burden, Lengthen Survival

Continuing nivolumab after first progression may reduce tumour burden and extend survival of metastatic renal cell carcinoma patients

medwireNews: Some patients with metastatic renal cell carcinoma (mRCC) may benefit from continuing with nivolumab therapy after RECIST-defined disease progression, suggests research published in JAMA Oncology.

Saby George, from Roswell Park Cancer Institute in Buffalo, New York, USA, and co-authors report subanalysis results for 36 trial participants with clear cell mRCC who received the immune checkpoint inhibitor at 0.3, 2.0 or 10.0 mg/kg doses at 3-week intervals for at least 6 weeks after first progression.

The patients – all of whom had previously received at least one anti-angiogenic agent for metastatic disease – continued with nivolumab as long as they tolerated treatment and showed clinical benefit, defined as an immune-related partial response or stable disease.

Fourteen percent of the group had achieved an objective response to nivolumab therapy and their median progression-free survival (PFS) was 4.2 months before first progression, the researchers observe. The corresponding outcomes for 92 trial participants who ended nivolumab treatment at first progression were 16% and 2.6 months.

In all, 69% of patients continuing with nivolumab showed tumour reduction or target lesion stabilisation after their initial progression, including 12 who had a greater than 30% reduction in burden, meeting RECIST version 1.1 criteria for response.

Median overall survival from 6 weeks after first progression for patients who continued with nivolumab was 22.5 months versus 12.3 months for the participants who ended nivolumab therapy.

Continuation of nivolumab was associated with a higher rate of treatment-related adverse events (81 vs 66%) but after adjusting for duration of treatment exposure, the incidence of side effects was lower in the patients who received treatment after first progression than those who did not, at an incidence of 322.9 versus 518.7 events per 100 patient–years.

“On the basis of these findings, larger-scale analyses and/or clinical studies of nivolumab treatment beyond RECIST defined first progression in patients with mRCC are warranted”, the authors conclude.

“Additional data may aid in the development of guidelines to help ensure optimal use of the new class of immunotherapy in RCC.”

Kim Margolin, from City of Hope National Medical Center in Duarte, California, USA, writes in an associated comment that the “large differences” in median PFS after first progressive disease “appear to support the validity of decisions to continue therapy in patients judged to have benefited despite objective [progressive disease].”

But she suggests the similar objective response rates in the two patient groups “seem at odds” with the longer median PFS for the continuing patients and the RECIST partial response decrease reported in 12 of the patients.

“Included among the unanswered questions are the role of prior therapy in nivolumab’s effects, because many such patients receive antiangiogenic therapies with immunopotentiating properties; the optimal duration of therapy in responders; and better methods to identify patients who need and will benefit from long-term programmed cell death 1 (PD-1) blockade”, she writes.

“Even the importance of programmed cell death 1 ligand (PD-L1) expression on tumor, which has been associated with but not required for response to PD-1 blockade, is complex due to variations in methods as well as between primary tumors and metastases and between metastases from different sites and at different points in time.”

References

George S, Motzer RJ, Hammers HJ, et al. Safety and efficacy of nivolumab in patients with metastatic renal cell carcinoma targeted beyond progression. A subgroup analysis of a randomized clinical trial. JAMA Oncol 2016; Advance online publication 12 May. doi:10.1001/jamaoncol.2016.0775

Margolin K. Treatment of renal cell cancer with programmed cell death 1 blockade. How much is enough? JAMA Oncol 2016; Advance online publication 12 May. doi:10.1001/jamaoncol.2016.0876.

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