Time to treatment failure (TTF) and treatment beyond progression (TBP) as survival outcome and therapeutic strategy of clinical benefit in pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab: a subanalysis of Meet-URO 15 study.

Background: Immunotherapies exhibit specific response patterns in contrast to chemotherapy and targeted therapy. Indeed, some patients experience response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefitis observed. As a result, calculating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy. Methods: The Meet-URO 15 study was a multicentric retrospective analysis on 571 pretreated mRCC patients receiving nivolumab. TTF was defined as the interval from the start of immunotherapy to discontinuation due to definitive disease progression or death. The study compared TTF to PFS and evaluated the predictive accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TTF and PFS. In addition, response and survival outcomes between TBP patients and non-TBP patients were assessed. Results: Overall, 571 mRCC patients were included in the analyses (PMID: 34046089). Median TTF was 8.9 months (range: 7.2-10.2), while mPFS was 7.2 months (range: 5.8- 8.6). The Meet-URO score outperformed the IMDC score in predicting both TTF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59). TBP patients had a higher overall response rate (34.4% vs 23.6%; p=0.035) and disease control rate (61.3% vs 54.8%; p=0.30). Interestingly, TBP patients had longer TTF (25.0 vs 10.7 months; p<0.001) and overall survival (42.5 vs 26.7 months; p<0.001) but had similar PFS compared to non-TBP patients. In TBP patients, a median delay of 13.2 months (range: 6-20.4) from the first to the definitive disease progression was observed (25 vs 1.8 months), whereas non-TBP patients had overlapped TTF and PFS (10.8 months). Conclusions: In this analysis, we found a 2-month difference between mTTF and mPFS in pretreated mRCC patients receiving nivolumab. However, TBP patients had significantly better outcomes, including a higher ORR (+10%), onger TTF (+13 months), and longer OS (+15 months). Furthermore, the Meet-URO score was found to be a more reliable predictor of TTF and PFS compared to IMDC score.