Heather McArthur, MD, MPH, on Immunotherapy for High-Risk, Early-Stage Breast Cancer

At IBC West, we recently discussed the application of immune therapy with curative intent for ear-ly stage breast cancer. We talked about the high risk of distant recurrence in patients with triple negative breast cancer. That is breast cancer that's lacking both hormone receptors and HER2 pro-tein. About a third of those patients are at risk of distant recurrence or metastatic breast cancer within two to three years of diagnosis, which is associated with a 12 to 18 month life expectancy. So devastating disease. So we were very excited when we saw the impact of checkpoint inhibitor mediated immune therapy in the metastatic setting. And whenever we see innovation in the met-astatic setting, we typically apply those same strategies in the curative intent setting. And that's what we did with the Keynote 522 study. This was a study that looked at preoperative chemother-apy with or without checkpoint inhibitor therapy in the form of pembrolizumab for triple negative breast cancer. And we saw at the initial analysis of 14% improvement in pathologic complete response rate that was agnostic of PDL1 expression. So the benefit was seen in both PDL1 and PDL1 negative tumors with a 7.7% improvement in event-free survival at three years. And we recently saw an update from that analysis with a 9% improvement in event-free survival at five years. So that became a standard of care. We're still refining our understanding about who needs immune therapy and who benefits from immune therapy and whether all of the benefit is conferred with preoperative ad-ministration with chemotherapy versus postoperative. We saw the results from the Impassion 030 study. This was a randomized phase three study that was looking at patients with triple-negative breast cancer who had upfront surgery and received adjuvant chemotherapy with or without checkpoint inhibitor therapy in the form of atezolizumab. And we reported negative results from that study. So no improvement in invasive disease-free sur-vival or overall survival in that environment. And the SWOG 1418 study is still pending. That's a study that looks at adjuvant pembrolizumab as monotherapy in patients at high risk, so those who had residual disease after neoadjuvant therapy. So at the present time, the standard of care for tri-ple negative breast cancer, that's high risk, is the Keynote 522 regimen, which is preoperative chemotherapy with pembrolizumab. And then patients receive pembrolizumab in the adjuvant set-ting to complete a year. There are a number of studies that are looking at escalation or deescala-tion strategies, specifically treatment optimization strategies. So for patients who have residual disease after preoperative therapy, there are several studies that are ongoing looking at combining these novel antibody drug conjugates, which have been paradigm changing in the metastatic dis-ease setting and adding those into checkpoint inhibitors in the curative intent setting. And then for those patients who achieve a complete response to neoadjuvant therapy, those pa-tients are at a very high rate of cure. And so potentially those patients don't need any more adju-vant therapy. So deescalation strategies in that setting. And then we're also looking at neoadjuvant strategies, looking at combining antibody drug conjugate with immune therapy in the Tropian Breast 04 study, going head-to-head against the Keynote 522 standard of care regimen. So a lot of research activity in that space. We've also recently seen updates from randomized phase three tri-als looking at immune therapy for the treatment of estrogen receptor positive early stage breast cancer. So the Keynote 756 study enrolled patients with grade three, stage two or three estrogen receptor positive early stage disease and randomized them to receive neoadjuvant chemotherapy with or without pembrolizumab. And we saw from that study an 8.5% improvement in pathologic complete response rate. The event-free survival from that study is still forthcoming, so highly anticipated data. And then we also recently saw data from the Checkmate 7FL study, which was originally designed with a patho-logic complete response and event-free survival co-primary endpoint, but was altered during the course of the study when the adjuvant CDK data was reported to have just the pathologic complete response rate as the primary endpoint with a 10.5% improvement in pathologic complete response in that study. And I also touched on the application of immune therapy and HER2 positive disease. So we've talked about triple negative disease, estrogen receptor positive disease, and we've under-taken a study looking at neoadjuvant therapy with a deescalated chemotherapy backbone. So Paclitaxel alone with HER2 directed therapy, with or without pembrolizumab, and are hoping to present that data to you later this year. So it's a very exciting time for the treatment of breast cancer with potential indications for immune therapy across all different subtypes.