medwireNews: Extended follow-up data from the KEYNOTE-564 study show that adjuvant pembrolizumab continues to offer a disease-free survival (DFS) benefit over placebo in people with renal cell carcinoma (RCC) at an intermediate-high or high postsurgery recurrence risk.
Speaking at the 2022 ASCO Genitourinary Cancers Symposium in San Francisco, California, USA, Toni Choueiri (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) said that the study “further supports adjuvant pembrolizumab as a new standard of care for patients with RCC with risk features for recurrence.”
The primary analysis of the study, previously reported by medwireNews, revealed that adjuvant pembrolizumab, started no more than 12 weeks postsurgery, reduced the risk for disease recurrence or death by a significant 32% versus placebo after 24 months of follow-up.
The current analysis included a further 6 months of data.
Choueiri reported that, at 30 months, the risk for recurrence or death was a significant 37% lower among the 496 participants who were randomly assigned to receive pembrolizumab 200 mg every 3 weeks for approximately 1 year than among the 498 individuals given placebo.
Median DFS was not reached in either group, but the updated DFS rate at 24 months was an estimated 78.3% with pembrolizumab versus 67.3% with placebo.
Choueiri noted that the benefits of pembrolizumab were observed across all recurrence risk subgroups.
For individuals at intermediate-high risk for recurrence, defined as pT2, grade 4 or sarcomatoid, N0, M0 disease or pT3, any-grade, N0, M0 disease, adjuvant pembrolizumab use was associated with a significant 32% lower risk for recurrence or death.
For those with high recurrence risk (pT4, any-grade, N0, M0 disease or any pT, any-grade, N+, M0 disease), adjuvant pembrolizumab lowered the risk by a significant 40%, while the risk was a significant 72% lower versus placebo among the participants with M1 but no evidence of disease after surgery.
So far, only 33% of deaths needed for final overall survival (OS) analysis have occurred, but the estimated OS rate at 24 months was 96.2% with pembrolizumab versus 93.8% with placebo, said Choueiri.
He added that no new safety signals were observed during the additional follow-up period and late-onset treatment-related adverse events were rare.
Discussant Daniel Geynisman, from the Fox Chase Cancer Center in Philadelphia, Pennsylvania, USA, said that the KEYNOTE-564 study has led to “great progress” in the field of perioperative RCC “but more work needs to be done.”
In particular, Geynisman commented that the optimal treatment duration for adjuvant immunotherapy still needs to be determined, as does the protocol for how to treat someone who recurs after adjuvant immunotherapy.
He also asked whether it will ever be possible to show a significant improvement in OS given that patients move on to different therapies post progression, and also whether it will reverse practice if a difference is not shown – he “doubts it.”
Finally, Geynisman said that there is a need for better biomarkers to tailor treatment recommendations.
“The FDA label is broad and we have to be careful not to overextend the use to low-risk patients or non-clear-cell patients although some will debate this,” he remarked.
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