Charles G. Drake, MD, PhD

Formal discussant of the GeparNuevo presentation, Charles G. Drake, MD, PhD, of the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, New York, said, “It is important that neoadjuvant immunotherapy combinations are being studied. There is a lot of enthusiasm for this approach. If you do the math, there are at least nine ways to combine agents. You can treat at the same time, sequentially, and as phased treatment.” 

Dr. Drake continued, “This trial compared combinatorial treatment to phase treatment, using a window of durvalumab given before treatment started. The trial was almost positive. It is clear that patients who got short monotherapy 2 weeks prior to combinatorial treatment did better. This needs to be investigated further.” 

‘Promising Area of Research’

“This study suggests that the use of checkpoint inhibitor therapy may improve response rates for triple-negative breast cancer in the curative setting. It did not show significantly improved response rates across the board, but a subset analysis suggests that the ‘window’ before chemotherapy may provide an opportunity to prime the immune response,” said Hatem H. Soliman, MD, of Moffitt Cancer Center, Tampa, Florida. 

“Patients with preexisting high tumor-infiltrating lymphocyte levels may also do better with this approach. It is unlikely that durvalumab unleashed a new immune response during the 2-week window in this trial,” he added.

Hatem H. Soliman, MD

Dr. Soliman is an I-SPY 2 investigator and was involved in the pembrolizumab (Keytruda) neoadjuvant study. “In I-SPY 2, we used pembrolizumab/chemotherapy and saw a similar effect—a higher response rate compared with the control arm. These two trials taken together show promising and tantalizing hints about how we might go forward. I would caution that these are preliminary results and not a ‘slam dunk.’ This is a promising area of research in a hard-to-treat type of breast cancer, and we need further trials to be sure the findings are not a ‘flash in the pan,’” Dr. Soliman continued. 

“The improved response rate in the ‘window’ cohort should influence the design of future trials. We need to study whether priming the inflamed tumor before hitting it with chemotherapy will improve outcomes,” he stated.

Several groups, including the I-SPY 2 investigators, are now discussing the design of future trials based on these phase II data.

“When combining a checkpoint inhibitor with chemotherapy, dose and schedule seem to matter. You can have too much chemotherapy or too little—the ‘Goldilocks’ effect. The dose of nab-pacltiaxel (Abraxane) used in GeparNuevo was not necessarily the optimal dose,” he added. ■

DISCLOSURE: Dr. Drake reported no conflicts of interest. Dr. Soliman has been a consultant for Novartis, AstraZeneca, Eli Lilly, and Eisai.