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- Title
How to optimize the use of adjuvant pembrolizumab in renal cell carcinoma: which patients benefit the most?
- Authors
Fallara, Giuseppe; Larcher, Alessandro; Rosiello, Giuseppe; Raggi, Daniele; Marandino, Laura; Martini, Alberto; Basile, Giuseppe; Colandrea, Gianmarco; Cignoli, Daniele; Belladelli, Federico; Re, Chiara; Musso, Giacomo; Cei, Francesco; Bertini, Roberto; Briganti, Alberto; Salonia, Andrea; Montorsi, Francesco; Necchi, Andrea; Capitanio, Umberto
- Abstract
Purpose: The KEYNOTE-564 trial showed improved disease-free survival (DFS) for patients with high-risk renal cell carcinoma (RCC) receiving adjuvant pembrolizumab as compared to placebo. However, if systematically administered to all high-risk patients, it might lead to the overtreatment in a non-negligible proportion of patient. Therefore, we aimed to determine the optimal candidate for adjuvant pembrolizumab. Methods: Within a prospectively maintained database we selected patients who fulfilled the inclusion criteria of the KEYNOTE-564. We compared baseline characteristics and oncologic outcomes in this cohort with those of the placebo arm of the KEYNOTE-564. Regression tree analyses was used to generate a risk stratification tool to predict 1-year DFS after surgery. Results: In the off-trial setting, patients had worse tumor characteristics then in the KEYNOTE-564 placebo arm, i.e. there were more pT4 (5.4 vs. 2.7%, p = 0.046) and pN1 (15 vs. 6.3%, p < 0.001) cases. Median DFS was 29 (95% CI 21–35) months as compared to value not reached in KEYNOTE-564 and 1-year DFS was 64.2% (95% CI 59.6–69.2) as compared to 76.2% (95% CI 72.2–79.7), respectively. Patients with pN1 were at the highest risk of 1-year recurrence (1-year DFS 28.6% [95% CI 20.2–40.3]); patients without LNI, but necrosis were at intermediate risk (1-year DFS 62.5% [95% CI 56.9–68.8]); those without LNI and necrosis were at the lowest risk (1-year DFS 83.8% [95% CI 79.1–88.9]). LVI substratification furtherly improved the accuracy in the prediction of early recurrence. Conclusions: Patients potentially eligible for adjuvant pembrolizumab have worse characteristics and DFS in the off-trial setting as compared to the placebo arm of the KEYNOTE-564. Patients with either LNI or necrosis were at the highest risk of early-recurrence, which make them the ideal candidate to adjuvant pembrolizumab.
- Subjects
PEMBROLIZUMAB; REGRESSION trees; PROGRESSION-free survival
- Publication
World Journal of Urology, 2022, Vol 40, Issue 11, p2667
- ISSN
0724-4983
- Publication type
Article
- DOI
10.1007/s00345-022-04153-6