ASCO 2022 | Exploratory analysis of KEYNOTE-522: EFS after neoadjuvant pembro + chemo Vs chemo for early TNBC
Lajos Pusztai, MD, DPhil, Yale School of Medicine, New Haven, CT, provides an overview on the exploratory analysis of the Phase III KEYNOTE-522 (NCT03036488) trial on event-free survival (EFS) by residual cancer burden after neoadjuvant pembrolizumab plus chemotherapy versus placebo plus chemotherapy for early triple-negative breast cancer (TNBC). The analysis included distributing residual cancer burden (RCB) into four categories of residual disease corresponding to pathologic complete response (pCR), from RCB0 corresponding to no residual disease up to RCD3 relating to extensive residual disease. The final results demonstrate a continued improvement in pCR rate at 8%, although this was less than observed in the primary analysis where a 13% improvement was shown. A significant improvement in event-free survival (EFS) was observed in the RCD2 category, corresponding to patients with moderate levels of residual disease deriving benefit from pembrolizumab in the neoadjuvant followed by the adjuvant setting, indicating the benefit of pembrolizumab extends beyond increasing pCR rate. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.
Transcript (edited for clarity)
So KEYNOTE-522 was the first large randomized trial that tested pembrolizumab together with new adjuvant chemotherapy followed by an adjuvant phase in triple-negative disease. What we present today is the final pathological COVID response rate results from the trial, including the entire population of about 1100 patients, as well as the distribution of the residue cancer burden. The residue cancer burden is the metric of the extent of residue disease that survived the preoperative chemotherapy and we created three categories, actually four categories, our CB0 corresponding to no residue disease or pathologic with response, CB1 sort of minimal residue disease, CB2 kind of moderate amount of residue disease...
So KEYNOTE-522 was the first large randomized trial that tested pembrolizumab together with new adjuvant chemotherapy followed by an adjuvant phase in triple-negative disease. What we present today is the final pathological COVID response rate results from the trial, including the entire population of about 1100 patients, as well as the distribution of the residue cancer burden. The residue cancer burden is the metric of the extent of residue disease that survived the preoperative chemotherapy and we created three categories, actually four categories, our CB0 corresponding to no residue disease or pathologic with response, CB1 sort of minimal residue disease, CB2 kind of moderate amount of residue disease. And CB3 has extensive residue disease. The most important finding of the study really is that the pembrolizumab benefit extends beyond increasing pathological compliance rate. In the final analysis, we continue to see an improvement in the pathological compliance response rate, but it’s less than during the first interim analysis, which was the primary analysis.
So the difference is about an 8% improvement in the pathological compliance rate relative to the 13% of the first time. However, the event free survival curves show that there is a significant improvement in event, free survival in the RCB two categories.
So patients with residue disease, that’s moderate amount, still derived a huge amount of benefit from pembrolizumab in the new adjuvant followed by the adjuvant setting. So I think the most important message really is that pembrolizumab provides benefit beyond improving pathological CR to alone.
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