FDA Approves Avelumab/Axitinib for Frontline RCC

The FDA has approved the combination of avelumab (Bavencio) and axitinib (Inlyta) for the frontline treatment of patients with advanced renal cell carcinoma.¹

The approval is based on results from the pivotal phase III JAVELIN Renal 101 trial, which showed that the combination was associated with a 31% reduction in the risk of disease progression or death compared with sunitinib (Sutent) in an intent-to-treat population (ITT) of patients with treatment-naïve advanced RCC, regardless of PD-L1 expression.²

"As we look to continue to improve outcomes for people with advanced RCC, new treatment approaches have the potential to benefit patients," said lead JAVELIN Renal 101 study investigator Robert J. Motzer, M.D., Jack and Dorothy Byrne Chair in Clinical Oncology, Memorial Sloan Kettering Cancer Center, in a press release. "With today’s FDA approval of avelumab in combination with axitinib, we can now offer patients with advanced RCC a first-line treatment option that combines a PD-L1 immunotherapy with a well-known VEGFR TKI to provide a significant reduction in the risk of disease progression or death and doubling of the response rate compared with sunitinib."

In the JAVELIN Renal 101 study, 886 patients with advanced or metastatic RCC were randomized 1:1 to receive 10 mg/kg of avelumab intravenously every 2 weeks plus 5 mg of oral axitinib twice daily in 6-week cycles or 50 mg of oral sunitinib once daily for a 4-weeks-on/2-weeks-off schedule. Patients with all MSKCC/Motzer Criteria with good- (21%), intermediate- (62%), and poor-risk disease (16%) were included.

The overall population included 560 (63.2%) PD-L1—positive patients. In the PD-L1–positive group, 270 patients received the combination and 290 patients were treated with sunitinib. In the overall group, 442 patients were treated with the combination while 444 received sunitinib. The primary endpoints were progression-free survival (PFS) by blinded independent central review and overall survival (OS) in the PD-L1–positive group; secondary endpoints were PFS and OS in the overall population irrespective of PD-L1 status, ORR, and safety.

Results showed that, in the PD-L1—positive population, the median PFS was 13.8 months (95% CI, 11.1-NE) with avelumab/axitinib compared with 7.2 months (95% CI, 5.7-9.7) with sunitinib, leading to a 39% reduction in the risk of disease progression or death (HR, 0.61; 95%, 0.475-0.790; P <.0001). The ORR with the combination was 55.2% (95% CI, 49.0-61.2), which included 4 complete responses (CRs) and 51 partial responses (PRs); the ORR with sunitinib was 25.5% (95% CI, 20.6- 30.9). Twenty-seven patients in the combination arm had stable disease (SD) and 11 had progressive disease (PD).

In the overall population, the median PFS with the combination of avelumab and axitinib versus sunitinib was 13.8 months (95% CI, 11.1-NE) and 8.4 months (95% CI, 6.9-11.1), respectively (HR, 0.69; 95% CI, 0.563-0.840; 2-sided P = .0002). Moreover, the ORR with avelumab/axitinib was 51.4% (95% CI, 46.6-56.1) and 25.7% (95% CI, 21.7-30.0) with sunitinib. In the combination arm, the ORR included 3 CRs and 48 PRs; 30 patients had SD and 12 patients had PD.

In the PD-L1—positive and overall population arms, 73% and 70% of patients remained on avelumab/axitinib treatment, respectively, versus 65% and 71% of those on sunitinib. Median duration of response was not yet reached in either treatment arm in either population.

At a follow-up for median OS of 19 months, the OS endpoint remain immature with 27% of deaths in the ITT population. Pfizer, which co-develops avelumab with Merck, stated in a press release that the trial is continuing as planned.

Regarding safety, the immunotherapy/TKI regimen was found to be favorable. Fifty-one (4%) patients on the combination arm and 48 (7%) patients on the sunitinib arm experienced grade 3/4 treatment-related adverse events (TRAEs), the most common being diarrhea (5% vs 3%). All-grade TRAEs were similar between arms. Four percent of TRAEs led to avelumab/axitinib discontinuation versus 8% with sunitinib; 1 patient on avelumab/axitinib died due to TRAEs.

Grade ≥3 TRAEs were reported in 71.2% of patients in the combination arm versus 71.5% of patients in the sunitinib arm, and led to treatment discontinuations in 22.8% versus 13.4%, respectively.

"Today’s approval of Bavencio in combination with Inlyta builds on Pfizer’s long heritage in bringing innovation to the RCC community with the hopes of making a significant and meaningful impact on the lives of patients," Andy Schmeltz, global president, Pfizer Oncology. "For more than 12 years, Pfizer has led the field in its commitment to developing new treatments for patients with advanced kidney cancer."

Moreover, the European Medicines Agency validated a Type II variation application for the combination of avelumab and axitinib in advanced RCC in March 2019. A supplemental application for the combination for patients with unresectable or metastatic RCC was submitted in Japan in January 2019.

References

1. FDA Approves Bavencio (Avelumab) Plus Inlyta (Axitinib) Combination for Patients With Advanced Renal Cell Carcinoma. Pfizer Oncology. Published May 14, 2019. https://on.pfizer.com/2HtdCzF. Accessed May 14, 2019.
2. Motzer RJ, Penkov K, Hannen JBAG, et al. JAVELIN Renal 101: a randomized, phase III study of avelumab + axitinib vs sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC). In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA6_PR.