Sherene Loi, MD, PhD
Formal discussant Sherene Loi, MD, PhD, Professor of Cancer Therapeutics at the Peter MacCallum Cancer Centre, Melbourne, Australia, characterized the results of KEYNOTE-522 as “exciting.”
“This is the first phase III neoadjuvant study in triple-negative breast cancer. Despite breast cancer not being considered immunogenic, atezolizumab has been approved for programmed cell death ligand 1 (PD-L1)-positive triple-negative breast cancer in advanced disease. The data suggest that we need enrichment of preexisting immunity in this disease,” Dr. Loi said.
“The most interesting data from KEYNOTE-522 relate to PD-L1 expression, which appears to be prognostic, since the pathologic complete response rate is higher in the PD-L1–positive patients independent of treatment arm,” she commented. She noted that unlike in advanced disease where antitumor activity has only been seen in the PD-L1–positive group, in this study, while only 20% of the study population, the relative benefit for pathologic complete response rate increase in PD-L1–negative patients appeared greater than in PD-L1–positive patients.
“It will be important to wait for mature data from this trial before applying these results to patient selection. Immune-related adverse events can be lifelong and permanent. They can include hypothyroidism, hyperthyroidism, type 1 diabetes, and possibly unknown effects on fertility,” Dr. Loi told listeners.
Remaining questions include whether the pathologic complete response rate will translate to event-free survival with longer follow-up and whether all patients with early-stage triple-negative breast cancer will need this intensive regimen.
“We need to wait for longer survival data from KEYNOTE-522 and results from other neoadjuvant studies. We also need to figure out the dose and scheduling with immunotherapy and chemotherapy, identify the best chemotherapy backbone, and the best duration of therapy. High levels of PD-L1 expression may allow room for chemotherapy de-escalation when a checkpoint inhibitor is added. And we await the biomarker analysis from this trial to inform patient selection,” Dr. Loi stated. ■
DISCLOSURE: Dr Loi has financial relationships with Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Puma Biotechnology, and Roche/Genentech. She has also served as an uncompensated consultant to AstraZeneca, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche/Genentech, and Seattle Genetics. She has served as a paid consultant (to her institution) for Aduro Biotech.
Immunotherapy has changed the treatment paradigms for melanoma, lung cancer, bladder cancer, and renal cancer. Now, checkpoint inhibitor therapy is making inroads in triple-negative breast cancer—one of the most difficult-to-treat aggressive types of breast cancer.
The addition of the checkpoint...