Insights for Oncologists on Follow-Up Data From KEYNOTE-B61 in nccRCC

Martin H. Voss, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses what community oncologists should takeaway from the the extended follow-up data of the phase 2 KEYNOTE-B61 study (NCT04704219) which assessed first-line pembrolizumab (Keytruda) plus lenvatinib (Lenvima) for patients with non-clear cell renal carcinomas (nccRCC).

According to findings presented at the 2024 Genitourinary Cancers Symposium, the combination demonstrated findings which were consistent with prior reports. Pembrolizumab with lenvatinib showed durable antitumor activity and a manageable safety profile among patients with advanced nccRCC, suggesting this combination continues to be supported as a first-line treatment option for patients with variant histologies of nccRCC.

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0:09 | I think that an important point to be made about the early data, which now is confirmed in this, is that there is strong efficacy for upfront combination therapy across most of the variants that we see less frequently in non-clear cell kidney cancer. GU oncologists and community oncologists are well aware of the strong antitumor effects that can be achieved within lenvatinib and pembrolizumab in conventional clear cell renal cell cancer. We see that confirmed here.

0:45 | If we review this data, which represents the largest prospective data set ever reported for an immuno oncology [IO]-based regimen in rare variant kidney cancer, and if we try to put that into context of what we know about the efficacy we can achieve with targeted therapies alone or with PD-1 inhibition alone in papillary kidney cancers or non-clear cell variants as a whole, I think an argument can be made that combination therapy, be it that it's additive or synergistic, is more likely to achieve deep and tumor responses, and it has higher fidelity in terms of preventing upfront progression, in my opinion, than monotherapies.

1:35 | I do think that what community oncologists can take away from this is that there seems to be an added benefit for considering combinations in all patients with RCC, not only the clear cell RCC. I think there's 1 important exception to that, and we've seen that in other datasets. The chromophobe variant kidney cancer, while they had a clear benefit on this trial, stand out to have lesser responses, then all the other variants treated here. We've seen that again and again in IO-based data sets for this variant. I personally am inclined to think that the antitumor effect we see here, including tumor shrinkage that we see on the waterfall plot analysis for chromophore patients specifically here, is likely attributable to the kinase inhibitor, more so than the PD-1 inhibitor. I think it is mostly driven by lenvatinib. Those patients might benefit from other non IO treatments, including targeted combinations.