Bavencio-Inlyta Combination Shows Promise Across Subtypes of Renal Cell Carcinoma

Frontline use of Bavencio (avelumab) plus Inlyta (axitinib) reduced the risk of disease progression or death by 31 percent compared with the standard of care in patients with advanced renal cell carcinoma (RCC), according to an interim analysis of the JAVELIN Renal 101 trial.

Results, which were published recently in the New England Journal of Medicine, showed that the regimen extended median progression-free survival — or the length of time during and after treatment that a patient lives with the disease but it does not get worse – by more than five months (13.8 months vs. 8.4 months) compared with Sutent (sunitinib) as a first-line treatment for patients with advanced RCC (the most common form of kidney cancer), irrespective of PD-L1 expression.

Moreover, the objective response rate was doubled with the combination (51.4 percent vs. 25.7 percent) compared with Sutent. Of note, the study is ongoing and continues to evaluate overall survival.

"There is a significant need for patients with advanced RCC to prolong the time until the disease worsens beyond what tyrosine kinase inhibitors alone offer," principal investigator Robert J. Motzer, M.D., Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center in New York City, said in a press release. "The magnitude and consistency of (progression-free survival) and response rates seen thus far across populations in the JAVELIN Renal 101 study suggest that many different types of patients, including those with a favorable prognosis, could potentially derive benefit from this particular combination."

A previous single-group, phase 1b trial of Bavencio plus Inlyta showed promising results in patients with advanced RCC. Therefore, in this phase 3 pivotal trial, the researchers compared the combination regimen with Sutent, in hopes that it would improve outcomes among patients who were previously untreated for the disease.

In total, 886 patients were randomized one-to-one, to receive Bavencio intravenously every two weeks plus Inlyta orally twice daily (442 patients) or Sutent orally once daily for four weeks (444 patients). The primary endpoints of the study are progression-free and overall survival in patients with PD-L1-positive tumors. The researchers are also evaluating progression-free survival in the overall population, objective response rate and safety.

In addition, data recently presented at the 2019 Genitourinary Cancers Symposium in February showed that progression-free survival and objective response rates were consistent across patient subgroups. “What we found is that, independent of (high-risk) groups, the combination works in those with favorable, intermediate and poor prognoses,” senior and corresponding author Toni K. Choueiri, M.D., director of the Lank Center for Genitourinary Oncology at Dana-Farber in Boston, said in an interview with CURE. “We also found that responses are independent of responses taken by investigator assessment or by independent review. We looked at patients with prior nephrectomy, patients who smoked, patients with low BMI, and it seems that those results are consistent all around.”

Among the 560 patients with PD-L1-positive tumors (63.2 percent), the median progression-free survival was 13.8 months with the combination regimen, compared with 7.2 months with Sutent; and the objective response rates were 55.2 percent and 25.5 percent, respectively.

At a median follow-up for overall survival of 11.6 months and 10.7 months in the combination and Sutent groups, 37 patients and 44 patients had died, respectively. In total, 99.5 percent of patients in the Bavencio/Inlyta arm and 99.3 percent of those in the Sutent arm experienced side effects, which were only grade 3 or higher in 71.2 percent and 71.5 percent, respectively.

The most common treatment-related side effects in the Bavencia/Inlyta arm included hypertension (25.6 percent), diarrhea (6.7 percent), increased alanine aminotransferase level (6.0 percent) and hand—foot syndrome (5.8 percent).

Of note, there were fewer discontinuations due to side effects that occurred during treatment with the combination, compared with Sutent (7.6 percent vs. 13.4 percent).