Invited discussant of KEYNOTE-564, Pedro Barata, MD, MSc, FACP, of the University Hospital Seidman Cancer Center, Cleveland, said the reasons for the disparate results in these two adjuvant trials of checkpoint inhibitors were likely the result of many factors. “Factors such as histology, different drugs, duration of treatment, patient characteristics like high risk, sarcomatoid features, safety profile, likely all played a role,” he noted.

Regarding KEYNOTE-564, he stated: “This is the first PD-L1 inhibitor to show improved overall survival and disease-free survival across solid tumors. About 85% of those with documented disease recurrence got subsequent therapies, and over 5 years, a quarter of them got local therapies. This raises questions about the biology of these tumors,” he continued.

Pedro Barata, MD, MSc, FACP

Dr. Barata pointed out that about 50% of patients in the trial did not experience recurrence after surgery and that about 10% had long-term remissions. However, 40% did experience recurrence despite the use of pembrolizumab.

Clinical Implications

In selecting patients for adjuvant pembrolizumab, he noted, the benefit of immunotherapy is enriched in patients with sarcomatoid features and in patients who are PD-L1–positive. For clear cell carcinoma with oligometastasis, Dr. Barata suggested local therapy and a discussion about pembrolizumab. For patients without sarcomatoid features who are at high risk, adjuvant pembrolizumab should be considered.

“Patients often perceive their risk of recurrence to be higher than their doctors’, according to some surveys. How do we decide when to use adjuvant pembrolizumab? I would argue that patients live longer on adjuvant pembrolizumab, and that outbalances other factors such as adverse events and cost. The story is not over, and different approaches are out there,” Dr. Barata said.

“Clearly, pembrolizumab is a breakthrough for our patients. But we need to have better patient selection for adjuvant pembrolizumab,” he concluded.

DISCLOSURE: Dr. Barata reported financial relationships with AstraZeneca, AVEO, Bayer, Bristol Myers Squibb, Caris Life Science, Eisai, EMD Serono, Exelixis, Merck, and Pfizer; institutional relationships with Dendreon, AstraZeneca, Bayer, Caris Life Sciences, Merck, and Pfizer/Astellas; and has received institutional research funding from AVEO, Blue Earth Diagnostics, Exelixis, Merck, and Pfizer.