Abstract 3281
Background
In a phase 1b trial, 1L A + Ax had encouraging antitumor activity for patients (pts) with aRCC (Lancet Oncol. 2018;19:451).
Methods
Eligible pts with clear-cell aRCC, ECOG ≤ 1, and no prior systemic therapy were randomized 1:1 (stratified by ECOG and geographic region) to receive A 10 mg/kg IV Q2W + Ax 5 mg PO BID in 6-wk cycles or S 50 mg PO QD on schedule 4/2; all prognostic risk groups were included. Primary endpoints were progression-free survival (PFS; by blinded independent central review [BICR] per RECIST v1.1) and overall survival (OS) in pts with PD-L1+ tumors (≥ 1% of immune cells). Secondary endpoints included PFS by BICR and OS irrespective of PD-L1 expression, objective response (OR), and safety.
Results
As of 20 Jun 2018, 886 pts were randomized (A + Ax: N = 442; S: N = 444); of these, 21%/62%/16% had favorable/intermediate/poor IMDC risk criteria (not reported in < 1%). In 560 pts (63.2%) with PD-L1+ tumors, median PFS was 13.8 vs 7.2 mo in A + Ax vs S arms, respectively (HR = 0.61; p < .0001; Table). Median PFS in pts irrespective of PD-L1 expression was 13.8 vs 8.4 mo (HR = 0.69; p = .0001). PFS and OR results favored A + Ax in pts irrespective of PD-L1 expression and in all MSKCC/IMDC prognostic risk groups. OS data were immature at data cutoff (< 16% of pts with events). In A + Ax vs S arms, grade ≥3 treatment-emergent adverse events occurred in 71.2% vs 71.5% of pts and led to discontinuation of any study drug in 22.8% vs 13.4%; deaths due to study treatment toxicity occurred in 0.7% vs 0.2% of pts.
Pts with PD-L1+ tumors | A + Ax (N = 270) | S (N = 290) |
PFS per BICR (primary endpoint) Median (95% CI), mo Stratified hazard ratio (95% CI); 1-sided p value |
13.8 (11.1, not estimable) |
7.2 (5.7, 9.7) |
0.61 (0.475, 0.790); p < .0001 | ||
Confirmed objective response rate per BICR Objective response rate (95% CI), % Stratified odds ratio (95% CI); 1-sided p value |
55.2 (49.0, 61.2) |
25.5 (20.6, 30.9) |
3.732 (2.532, 5.371); p < .0001 | ||
Pts irrespective of PD-L1 expression | A + Ax (N = 442) | S (N = 444) |
PFS per BICR Median (95% CI), mo Stratified hazard ratio (95% CI); 1-sided p value |
13.8 (11.1, not estimable) |
8.4 (6.9, 11.1) |
0.69 (0.563, 0.840); p = .0001 | ||
Confirmed objective response rate per BICR Objective response rate (95% CI), % Stratified odds ratio (95% CI); 1-sided p value |
51.4 (46.6, 56.1) |
25.7 (21.7, 30.0) |
3.098 (2.300, 4.148); p < .0001 |
Conclusions
This randomized phase 3 trial met its primary objective of significantly improving PFS in pts with PD-L1+ aRCC treated with A + Ax vs S. PFS and OR benefit was also observed in pts irrespective of PD-L1 expression and across all prognostic risk groups. The safety profiles were consistent with those of prior studies of each drug. These results support A + Ax as a potential new 1L standard-of-care for pts with aRCC.
Clinical trial identification
Clinical Trial Number: NCT02684006
Editorial Acknowledgement
Medical writing support was provided by ClinicalThinking Inc., Hamilton, NJ, USA.
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