First-Line Avelumab Plus Axitinib Significantly Improves PFS in Advanced Untreated Renal Cell Carcinoma
A combination of the immune checkpoint blocker, avelumab, plus the tyrosine kinase inhibitor (TKI), axitinib, significantly improves progression-free survival (PFS) in previously untreated patients with advanced renal cell carcinoma (RCC) in a phase 3 study, according to results presented at ESMO 2018 Congress in Munich.
Despite available therapies, survival for patients with advanced RCC is less than 10% at 5 years post-diagnosis. The JAVELIN Renal 101 study was a phase 3 trial evaluating the efficacy of combining the PD-L1 inhibitor avelumab with the TKI axitinib as first-line treatment. This combination showed encouraging antitumor activity for patients with advanced RCC in a Phase 1b trial. “TKIs, and checkpoint blockers like avelumab, both may have potential immune-modulating functions that, when combined, may provide clinical benefit in patients with advanced RCC that exceeds the effects of the respective drugs alone, without compromising toxicity,” said Robert Motzer, presenter and study lead, Memorial Sloan Kettering Cancer Center, New York, NY.
The global, randomized trial included 886 untreated patients with advanced RCC. Intravenous avelumab in combination with oral axitinib were administered to 442 patients, while 444 patients in the comparator group received oral sunitinib. Primary endpoints were progression-free survival (PFS) and overall survival (OS) in patients with PD-L1-positive tumors (≥ 1%). Secondary endpoints included PFS and OS irrespective of PD-L1 expression, objective response (OR), and safety.
While OS data were immature at data cutoff (< 16% of pts with events), PFS and OR results favored the avelumab plus axitinib combination in all patients irrespective of PD-L1 expression and in all MSKCC/IMDC prognostic risk groups. In 560 patients with PD-L1-positive tumors, median PFS was 13.8 vs 7.2 months in the avelumab plus axitinib arm compared to the sunitinib arm (HR = 0.61; P < .0001). Median PFS in patients irrespective of PD-L1 expression was 13.8 versus 8.4 months (HR = 0.69; P = .0001) respectively, and confirmed objective response rate was 55.2 (CI 95%: 49.9, 61.2) and 25.5 (CI 95%: 20.6, 30.9) respectively.
|
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 |
||
The researchers reported that safety profiles were consistent with those of prior studies of each drug. Grade ≥3 treatment-emergent adverse events occurred in 71.2% vs 71.5% of patients, and led to discontinuation of any study drug in 22.8% vs 13.4% of patients, in the avelumab plus axitinib arm vs the sunitinib arm, respectively. Deaths due to study treatment toxicity occurred in 0.7% vs 0.2% of patients, respectively.
“JAVELIN Renal 101 is the first positive phase 3 study combining an immune checkpoint blocker with a TKI compared to TKI alone in the first line treatment of advanced RCC,” Dr Motzer said. “The findings support the potential of avelumab plus axitinib as a new treatment approach for patients with advanced RCC… whether tumor cells stained positive for PD-L1 or not.”—Kara Rosania
