Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
Toni K. Choueiri , Piotr Tomczak , Se Hoon Park , Balaji Venugopal , Tom Ferguson , Stefan N. Symeonides , Jaroslav Hajek , Yen-Hwa Chang , Jae-Lyun Lee , Naveed Sarwar , Antoine Thiery-Vuillemin , Marine Gross-Goupil , Mauricio Mahave , Naomi B. Haas , Piotr Sawrycki , Tian Zhang , Lei Xu , Kentaro Imai , Christian Heinrich Poehlein , Thomas Powles
Background: Adjuvant pembro prolonged disease-free survival (DFS) for patients (pts) with RCC at increased risk of recurrence after nephrectomy in the phase 3 KEYNOTE-564 study (NCT03142334). This post hoc exploratory analysis evaluated efficacy of adjuvant pembro in pt subgroups based on UISS and disease stage. Methods: Pts with histologically confirmed clear cell RCC (pT2, Grade [G] 4 or sarcomatoid, N0, M0; pT3 or pT4, any G, N0, M0; any pT, any G, N+, M0; or M1 NED) were randomly assigned 1:1 to receive pembro 200 mg IV or placebo (pbo) every 3 weeks for ≤17 cycles (~1 y). DFS was assessed by investigator. UISS risk groups were derived retrospectively from TNM stage, Fuhrman nuclear grade, and ECOG PS. UISS groups were intermediate risk (pT2, G4, N0, M0; pT3, G1, N0, M0; or pT3, G2-4, N0, M0, ECOG 0), high risk (pT3, G2-4, N0, M0, ECOG PS 1; pT4, any G, N0, M0; or N1, M0), or M1 NED. Other subgroups were evaluated based on disease stage. Results: Baseline characteristics were balanced within subgroups. Median follow-up was 30.1 mo (range 20.8-47.5). Of 994 enrolled pts, most had UISS intermediate risk (n = 732, 73.6%; pembro n = 359; pbo n = 373); 195 pts (19.6%; pembro n = 100; pbo n = 95) had UISS high risk, and 58 pts (5.8%; pembro and pbo n = 29 each) had M1 NED. In the UISS intermediate risk group, the hazard ratio (HR) for DFS was 0.65 (95% CI, 0.48-0.88; 24-mo rates, pembro: 81.5%, pbo: 72.4%). In the UISS high-risk group, HR for DFS was 0.77 (95% CI, 0.49-1.20; 24-mo rates, pembro: 65.0%, pbo: 55.9%). In the M1 NED group, HR for DFS was 0.28 (95% CI, 0.12-0.66; 24-mo rates, pembro: 78.4%, pbo: 37.9%). DFS by disease stage is in the Table. Conclusions: Consistent with the results of the intention-to-treat (ITT) population, adjuvant pembro prolonged DFS compared with pbo for all subgroups. Results of this exploratory analysis further support the use of adjuvant pembro after nephrectomy as standard of care for pts with RCC at increased risk of recurrence. Clinical trial information: NCT03142334.
DFS HR and 24-mo rates | Pembro | Pbo |
---|---|---|
ITT | N = 496 HR (95% CI): 0.63 (0.50-0.80) 24-mo: 78.3% | N = 498 - 24-mo: 67.3% |
Disease stage: T2, G4, N0, M0 and T3, G1-2, N0, M0 (33.0% of ITT) | n = 161 HR (95% CI): 0.79 (0.49-1.27) 24-mo: 83.5% | n = 167 - 24-mo: 78.3% |
T3, G3-4, N0, M0 (52.6% of ITT) | n = 258 HR (95% CI): 0.63 (0.45-0.88) 24-mo: 79.3% | n = 265 - 24-mo: 68.0% |
T4, N0, M0 (2.2% of ITT) | n = 11 HR (95% CI): 0.63 (0.17-2.36) 24-mo: 63.6% | n = 11 - 24-mo: 54.5% |
N1, M0 (5.4% of ITT) | n = 29 HR (95% CI): 0.57 (0.29-1.12) 24-mo: 42.8% | n = 25 - 24-mo: 27.4% |
M1 NED (5.8% of ITT) | n = 29 HR (95% CI): 0.28 (0.12-0.66) 24-mo: 78.4% | n = 29 - 24-mo: 37.9% |
AJCC TNM stage: Stage 2: pT2, N0, M0 (4.1% of ITT) | n = 22 HR (95% CI): 0.74 (0.30-1.83) 24-mo: 57.3% | n = 19 - 24-mo: 47.4% |
Stage 3: pT3, N0, M0 or pT1-3, N1, M0 (87.5% of ITT) | n = 432 HR (95% CI): 0.67 (0.52-0.88) 24-mo: 79.9% | n = 438 - 24-mo: 70.7% |
Stage 4: pT4, Any N, M0 or M1 NED (8.2% of ITT) | n = 41 HR (95% CI): 0.37 (0.19-0.74) 24-mo: 72.4% | n = 41 - 24-mo: 41.5% |
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Abstract Disclosures
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First Author: Toni K. Choueiri
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