Nivolumab, a fully human anti-PD-1 monoclonal antibody produced through recombinant DNA technology in Chinese hamster ovary cells, marks a milestone in breast cancer treatment. Recent years have witnessed a significant transformation in how we approach breast cancer care, with immunotherapy taking center stage. It promises to deliver enduring responses while keeping side effects manageable for an expanding patient population.

Though early-stage HR+/HER2- breast cancer generally has a more favorable outlook compared to triple-negative cases, the response rates to neoadjuvant chemotherapy (NACT) have been disappointingly low. Neoadjuvant immunotherapy, as observed in different arms of the I-SPY2 trial, holds the promise of improving these response rates. However, further investigation is needed to substantiate these benefits and their long-term impact. The ongoing randomized Phase III CheckMate 7FL trials are a pivotal effort to assess the potential of neoadjuvant and adjuvant nivolumab in combination with standard chemotherapy. These trials offer a unique opportunity to gain critical insights into the effectiveness of immunotherapy for ER+/HER2- breast cancer.

Data presented at ESMO 2023 revealed substantial improvements in pCR rates when using neoadjuvant nivolumab alongside chemotherapy, with these outcomes significantly surpassing those of the control group. Furthermore, the advantages associated with nivolumab were more pronounced in patients who were PD-L1+. Notably, during the neoadjuvant phase, the incidence of grade 3-4 treatment-related adverse events was similar across both treatment arms.

KOL insights

“Nivolumab is not currently approved for breast cancer. Although promising, the results from CheckMate 7FL show most benefit in PD-L1+ positive patients, which account for only around one-third of the 521 patients involved, so further research is needed to confirm the benefit of this combination therapy before it enters the clinic.”– Professor from the Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK.

Conclusion

The Phase III CheckMate 7FL trials, currently underway, represent a groundbreaking effort to assess the potential of integrating neoadjuvant and adjuvant nivolumab with standard chemotherapy. These trials offer a unique opportunity to gain vital insights into the effectiveness of immunotherapy in treating ER+/HER2– breast cancer. In patients with high-risk, ER+/HER2– primary breast cancer, the addition of nivolumab to neoadjuvant chemotherapy led to a statistically significant 10.5% increase in pCR rates. Furthermore, the RCB 0-1 rate saw a notable improvement of 9.2% with the incorporation of nivolumab, with the most significant benefits observed in patients with PD-L1≥ 1%. The safety of the nivolumab and neoadjuvant chemotherapy combination remained consistent with the known safety profiles of the individual treatments, and no new safety concerns emerged. Although there was a higher incidence of immune-mediated adverse events (IMAE), the overall safety profile aligned with expectations for nivolumab and chemotherapy.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to ER+/HER2-ve Breast Cancer-Market Report