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CancerNetwork® sat down with Robert A. Figlin, MD, at the 2021 ASCO Annual Meeting to discuss the results of the KEYNOTE-564 trial with adjuvant pembrolizumab in patients with resected clear cell renal cell carcinoma.
At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® spoke with Robert A. Figlin, MD, deputy director at Cedars-Sinai Cancer and genitourinary tumor chair of the Editorial Board of the journal ONCOLOGY®, about findings from the phase 2 KEYNOTE-564 trial (NCT03142334) with pembrolizumab (Keytruda) vs placebo in patients with histologically confirmed clear cell renal cell carcinoma following nephrectomy.
Although the data appear promising and have the potential to influence the standard of care in the future, Figlin noted that there are some concerns regarding data collection and questions left unanswered by the study’s results.
Late breaking abstract number 5 that was presented by Toni Choueiri, [MD,] from Dana-Farber, which looked at Keytruda in patients with high-risk resected disease, [demonstrated] an improvement in disease-free survival [DFS] when compared with placebo. [This] is a population of patients [who are] worth looking at and [this] is potentially practice changing. But there are a few observations that I would like to make…which were not really asked and addressed in the context of the discussion.
First of all, usually when we think about adjuvant treatment, we think about adjuvant treatment for high-risk, resected RCC where the only commercially available drug approved in that setting is sunitinib [Sutent] from the phase 3 S-TRAC trial [NCT00375674]. The trial that was presented by [Choueiri] included both high-risk, resected [disease], as well as a population of patients with known metastatic disease who were thought to have oligometastatic resections, rendering them disease free. I want to be clear that this is not a population of patients who [are] usually considered for adjuvant trials. In fact, it may skew the results in a way that favors the therapy. Why?
When one looks at the progression-free survival curves that were presented as part of ASCO, the curve separated very early and stayed separated over the course of the first 24 months. What one might want to ask is, even though about 6% of patients had metastatic disease that was resected, was the [immuno-oncology] therapy really benefiting that population without a clear signal yet in the high-risk, resected non-metastatic patient population? I think that the trial, while positive, is a bit flawed. Additionally, that could have been clarified with a better control of imaging—having blinded imaging at the beginning of the trial—to make sure that we all agree it was basically investigator-assessed outcomes. While I think that is important in general, one has to be very careful when [including] a population of patients who also have known, [biopsy-proven] metastatic disease. DFS, although possibly appropriate without independent radiologic review for a high-risk, resected patient [in the adjuvant setting], is generally not a form that we would take for the patients with known metastatic disease. [It was an] interesting trial [that was] potentially practice changing; certainly different than what we saw with targeted therapy in this setting; not yet in peer-reviewed publications for all of us to look at; and has some challenges that are going to make it a bit difficult to interpret. We are going to have to be looking for other adjuvant trials in a more ‘pure’ high-risk, resected population to assert that this is really practice changing.
Choueiri TK, Tomczak P, Park SH, et al. Pembrolizumab vs placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: randomized, double-blind, phase 3 KEYNOTE-564 study. J Clin Oncol. 2021;39(suppl 15):LBA5. doi:10.1200/JCO.2021.39.15_suppl.LBA5