The Impact of Biomarker-Driven Frontline Treatment in mRCC

Yann-Alexandre Vano, MD, Georges-Pompidou European Hospital, Paris, France, discusses what clinicians can take away from the results of the phase 2 BIONIKK trial (NCT02960906) that looked at treatment for patients with metastatic renal cell carcinoma (RCC) based on their biomarker test results. Patients were randomized 1:1 using permuted blocks of varying sizes to receive either nivolumab (Opdivo; n = 58), or nivolumab and ipilimumab (Yervoy; n = 101), labeled the ccrcc1 and ccrcc4 groups), or either an anti-VEGFR tyrosine kinase inhibitor (TKI; n = 40) or nivolumab and ipilimumab, called the ccrcc2 and ccrcc3 groups. These groups were based on the biomarkers observed in the patients allowing for clinicians to make tailored recommendations for these certain patients.

Reported findings showed that after a median follow up of 42.1 months the median overall survival (OS) was 3.4 months in the nivolumab arm (95% CI, 31.4-not reached [NR]), 52.7 months with nivolumab and ipilimumab (95% CI, 46-NR), and 38.1 months (95% CI, 33.2-NR) with TK. The objective response rate (ORR) was 29% (95% CI 16%–45%) in the nivolumab group compared with 39% (95% CI, 24%–55%) in the nivolumab and ipilimumab group (odds ratio [OR] 0·63; 95% CI 0.25–1.56).

Moreover, further comparisons in patient subgroups showed that in the ccrcc4 group of patients there was a 44% (95% CI 20%–70%) of patients on nivolumab compared with 50% (95% CI, 26%–74%) of patients with nivolumab and ipilimumab (OR, 0.78; 95% CI, 0.20–3·01). In the ccrcc2 group, the ORR was 50% (95% CI, 33%–67%) for patients on a VEGFR-TKI compared with 51% (95% CI, 34%–68%) for patients on nivolumab and ipilimumab (OR 0.95; 95% CI, 0.38–2.37).

Vano looks at how the ability to match patients with a more tailored treatment will give ana advantage to clinicians and provide an important step in the treatment of this patient population.

Transcription:

0:08 | First, is it feasible? Is it possible to make some smaller trials than phase 3 trials and big phase 3 trials launched by the industry? Is it possible to make a hypothesis and to verify this hypothesis with [a] limited randomized phase 2 trial. This is the first thing. Second, this approach seems to me more clever, to select treatments based on [on the] biomarker.

0:41 | I think it's what we need, because in first-line metastatic RCC we have plenty of options [and] we have a lot of combinations. We don't know clearly what the what to do [or] what to use, and this biomarker-based approach, I think, is a new way to improve the efficacy of this treatment in [a] particular subgroup of patients. I think it's very important.