First-line avelumab + axitinib tops sunitinib for advanced RCC
Patients with renal cell carcinoma (RCC) who received the first-line combination of avelumab and axitinib had longer progression-free survival (PFS) compared with those who received sunitinib, particularly those with PD-L1–positive tumours, according to findings of the phase III JAVELIN Renal 101* trial.
A total of 886 patients with previously untreated advanced clear cell RCC and ECOG performance status of 0 or 1 were randomized 1:1 to receive intravenous avelumab (10 mg/kg Q2W) plus oral axitinib (5 mg BID; median age 62 years, 72 percent male) or oral sunitinib (50 mg QD with a 4-week on, 2-week off schedule; median age 61 years, 78 percent male). Of these, 63.2 percent of patients (n=560) had PD-L1–positive tumours.
Among patients with PD-L1–positive tumours, PFS was significantly longer among avelumab plus axitinib (median follow up, 9.9 months) compared with sunitinib recipients (median follow up, 8.4 months; median, 13.8 vs 7.2 months, hazard ratio [HR], 0.61, 95 percent confidence interval [CI], 0.47–0.79; p<0.001). [ASCO GU 2019, abstract 544; N Engl J Med 2019;doi:10.1056/NEJMoa1816047]
These findings were comparable to that of the overall population where PFS also favoured the avelumab plus axitinib compared with sunitinib group (median, 13.8 vs 8.4 months, HR, 0.69, 95 percent CI, 0.56–0.84; p<0.001).
Patients with PD-L1–positive tumours who received avelumab plus axitinib also demonstrated a superior objective response rate (ORR) compared with those on sunitinib (55.2 percent vs 25.5 percent), again with similar findings to that of the overall cohort (51.4 percent vs 25.7 percent).
Overall survival in patients with PD-L1–positive tumours was proportionally but not significantly improved among avelumab plus axitinib (median follow up, 11.6 months) compared with sunitinib recipients (median follow up, 10.7 months; 13.7 percent vs 15.2 percent, HR, 0.82, 95 percent CI, 0.53–1.28; p=0.38), similar to that in the overall population (14.3 percent vs 16.9 percent, HR, 0.78, 95 percent CI, 0.55–1.08; p=0.14). Mean duration of response was >4 months longer in avelumab plus axitinib than sunitinib recipients, and PFS following next line of treatment also favoured avelumab plus axitinib over sunitinib recipients (not evaluable vs 18.4 months, HR, 0.56).
On-treatment adverse event (AE) incidence was similar between avelumab plus axitinib and sunitinib recipients (99.5 percent vs 99.3 percent), specifically grade ≥3 AEs (71.2 percent vs 71.5 percent). The most frequent grade ≥3 AE was hypertension, which occurred in 25.6 and 17.1 percent of avelumab plus axitinib and sunitinib recipients, respectively. AE-related discontinuations occurred in 7.6 and 13.4 percent of avelumab plus axitinib and sunitinib recipients, respectively. Three patients on avelumab plus axitinib and one on sunitinib died due to treatment-related toxicity.
Fewer patients on avelumab plus axitinib compared with sunitinib received subsequent treatment, be it drug therapy (20.8 percent vs 39.2 percent), radiation therapy (5.9 percent vs 8.1 percent), or surgery (1.8 percent vs 3.6 percent).
“JAVELIN Renal 101 demonstrated longer PFS and higher ORR with avelumab plus axitinib compared with sunitinib for treatment-naïve patients with advanced RCC … [and the] benefit was observed … regardless of PD-L1 status and in all prognostic risk groups,” said study author Dr Toni Choueiri from the Dana-Farber Cancer Institute, Boston, Massachusetts, US.
“[T]he magnitude of benefit with respect to [ORR] and PFS associated with avelumab plus axitinib as compared with sunitinib supports at least additive if not synergistic effects of the VEGF tyrosine kinase inhibitor–immune checkpoint inhibitor combination,” said Choueiri and co-authors.
“The results support avelumab plus axitinib as a new first-line standard of care for patients with advanced RCC,” concluded Choueiri, highlighting that follow up for OS results is ongoing.