Commenting on SAFIR02-IMMUNO for The ASCO Post, Kevin Kalinsky, MD, MS, Associate Professor of Medicine at ­NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, said the findings of the analysis were in accordance with other studies in metastatic breast cancer, but they came from a study that is rather unique. “It was part of a larger study that identified whether patients had a known actionable mutation,” he noted. “Those without mutations or who did not have accessible metastatic tissue for biopsy were enrolled in this immunotherapy-based arm. It was also unique in that patients were required to have a response to chemotherapy before going on to maintenance.”

Kevin Kalinsky, MD, MS

The one approval for immunotherapy in breast cancer is currently for the programmed cell death ligand 1 (PD-L1) inhibitor atezolizumab plus nab-paclitaxel as a front-line treatment for PD-L1–positive metastatic triple-negative breast cancer, he noted.

Who Benefits From Checkpoint Inhibition?

“First, one of the key findings was that the hormone receptor–positive population did not benefit from the PD-L1 inhibitor durvalumab, which is something that has been observed in other studies. Although the hope is to be able to enhance immunogenicity of this subtype of breast cancer, we now have another study demonstrating that for patients with metastatic hormone receptor–positive/HER2-negative disease, there is currently no benefit from checkpoint inhibition,” stated Dr. Kalinsky.

“Second, the study gave additional evidence of the clinical benefit in patients with PD-L1–positive metastatic triple-negative breast cancer, as was observed with atezolizumab in IMpassion130.¹ In addition, the benefit in SAFIR02 was observed with single-agent checkpoint blockade,” Dr. Kalinsky continued. “However, it is also worth reiterating that, although it is encouraging to see an overall survival advantage, this is a small patient population (only 82 patients).” Approximately 20% of all breast cancers are triple-negative, and about 40% of those express PD-L1, as per IMpassion130, he pointed out. “Thus, it gives further evidence that there is a subgroup of patients who seem to benefit from PD-L1 blockade.”

Whether there is additional benefit to using checkpoint inhibition as maintenance for patients who respond to upfront chemotherapy for metastatic disease, as compared with using it upfront along with chemotherapy in the front line-metastatic setting, is unknown but is “hypothesis-generating,” Dr. Kalinsky added. “The standard of care at this moment is to give nab-paclitaxel plus a PD-L1 inhibitor for patients with newly diagnosed PD-L1–positive metastatic triple-negative breast cancer. Could there be a subgroup who responds to chemotherapy, for whom we could de-escalate chemotherapy and just give a checkpoint inhibitor? That’s a future question. This sort of strategy would need to be evaluated in future trials.” 

DISCLOSURE: Dr. Kalinsky owns stock or other ownership interests in Array BioPharma, Novartis, and Pfizer; has served as a consultant or advisor for Amgen, AstraZeneca, bioTheranostics, Eisai, Genentech/Roche, Immunomedics, Ipsen, Lilly, Novartis, Odonate Therapeutics, and Pfizer; has participated in a speakers bureau for Lilly; has received institutional research funding from Acetylon, Amgen, Calithera Biosciences, CytomX Therapeutics, Genentech/Roche, Immunomedics, Incyte, Lilly, Novartis, Pfizer, Seattle Genetics, and Zeno Pharmaceuticals; has been reimbursed for travel, accommodations, or other expenses by Amgen, AstraZeneca, Genentech, Lilly, Novartis, and Pfizer.

REFERENCE

1. Schmid P, Adams S, Rugo HS, et al: Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379:2108-2121, 2018.