Editor's Note: The 6th Precision Oncology Summit and the 9th Individualized Breast Cancer Treatment Conference (2023 COMB) took place from December 23 to 26, 2023, combining both online and offline formats. During the event, Professor Fei Ma from the Cancer Hospital of the Chinese Academy of Medical Sciences delivered an insightful presentation titled "The Knowns and Unknowns of Breast Cancer Immunotherapy." Following his presentation, Oncology Frontier conducted an exclusive interview with Professor Ma to discuss the latest advancements in breast cancer immunotherapy.01
Oncology Frontier: Immunotherapy first made its foray into the treatment of triple-negative breast cancer (TNBC), with mixed success. Could you discuss the successful immunotherapy studies in early-stage TNBC and the insights they provide?
Professor Fei Ma: TNBC is characterized by distinct pathophysiological features, higher tumor mutational burden, and lymphocytic infiltration, and currently has limited treatment options, making it a suitable candidate for immunotherapy exploration. To date, immunotherapy has not only made significant advances in the treatment of advanced TNBC but also in the neoadjuvant and adjuvant stages of early-stage breast cancer (e.g., KEYNOTE-522 study, IMpassion 031 study). Studies on neoadjuvant immunotherapy for early-stage TNBC suggest that combining immunotherapy with chemotherapy can improve patients’ pathological complete response (pCR) rates and, in some cases, event-free survival (EFS) benefits. For early-stage TNBC patients, we recommend a strategy of combining immunotherapy with chemotherapy during the neoadjuvant treatment phase. On November 1, 2022, the PD-1 inhibitor pembrolizumab was approved by China’s National Medical Products Administration (NMPA) for use in combination with chemotherapy in the neoadjuvant treatment, followed by continued solo adjuvant therapy, for early-stage high-risk TNBC patients with a confirmed PD-L1 expression (CPS≥20). In the United States, the FDA has approved a broader indication for pembrolizumab, allowing its use combined with chemotherapy since November 2020 for treating locally recurrent unresectable or metastatic TNBC patients with PD-L1 expression (CPS≥10).
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Oncology Frontier: We’ve also seen the emergence of immunotherapy in the treatment of early-stage HR+/HER2- breast cancer, with higher pCR benefits from immunotherapy combined with chemotherapy compared to neoadjuvant chemotherapy alone (e.g., CheckMate 7FL study, KEYNOTE-756 study). How should we identify the patient population that benefits from combined immunotherapy and chemotherapy?
Professor Fei Ma: At international conferences in 2023, data from the CheckMate 7FL and KEYNOTE-756 studies revealed the presence of immunotherapy in early-stage HR+/HER2- breast cancer treatment, showing improved pCR rates in patients. This indicates that if the right patient population is selected for HR+/HER2- breast cancer treatment, immunotherapy can be beneficial. However, these studies still have relatively short follow-up periods, and it remains to be seen whether the increased pCR rates will translate into EFS benefits. Future analysis is needed to determine whether the pCR or non-pCR populations can benefit from immunotherapy. Both studies selected patients with higher tumor grades for inclusion, further suggesting that in clinical practice, for HR+/HER2- breast cancer patients receiving immunotherapy, we should select the appropriate treatment population based on the characteristics of patients included in the studies. Moving forward, we will also select patients with higher added value indexes and poorer prognosis for neoadjuvant immunotherapy studies based on their immunohistochemistry results.
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Oncology Frontier: At this COMB conference during the “Expert Discussions” segment, you delivered a lecture on “The Knowns and Unknowns of Breast Cancer Immunotherapy.” What do you see as the pressing issues in the field of immunotherapy for HR+/HER2- advanced breast cancer? What directions are worth exploring in the future?
Professor Fei Ma: In the academic exchange at the COMB conference, I discussed the three stages of development in breast cancer immunotherapy, which can also be summarized as the three stages of HR+/HER2- breast cancer immunotherapy. For breast cancer immunotherapy, I summarize the first stage as follows: “Last night the west wind withered the green trees. Alone on the high tower, I looked to the ends of the horizon.” Although we have made many explorations and efforts, looking back, we did not achieve good results, but our exploration of immunotherapy has not stopped.
The second stage: “My belt widens, but I regret it not, for the sake of her who has worn me down.” As for the breast cancer immunotherapy combined treatment protocols, past research shows that the combination of eribulin and pembrolizumab did not achieve good treatment effects. Could other chemotherapy drugs or administration methods possibly bring us better treatment efficacy? Our team has also explored this, and the related results were selected for an oral presentation at the 2023 SABCS conference (study title: Efficacy and safety of toripalimab plus metronomic chemotherapy in HER2 negative metastatic breast cancer: a multicenter phase II trial based on a Bayesian adaptive randomized design). In this study, we found that the efficacy and safety of different immunotherapy combination schemes varied. Combination methods include conventional chemotherapy such as platinum drugs with immunotherapy, metronomic chemotherapy with immunotherapy, and anti-angiogenic drugs bevacizumab with immunotherapy. Ultimately, we found that using a multiple-drug metronomic chemotherapy with immune checkpoint inhibitors can provide patients with a better ORR rate, which also gives us more confidence in treatment. Furthermore, we also saw signs of patient benefits from the combination of CDK4/6 inhibitors and immunotherapy. Therefore, I believe that even if “for the sake of her who has worn me down,” it is worth it on the path of immunotherapy.
I am confident that as we deepen our understanding of the mechanisms of immunotherapy and gradually delve deeper, one after another unknown problem will be solved. One day in the future, we will enter the third stage: “Suddenly looking back, the person is there at the dimly lit place.” But for breast cancer patients, the future of immunotherapy will also generate new clinical needs and puzzles on the basis of solving one unknown after another, and we still need to continue our exploration. Therefore, the future of immunotherapy should be a state where the known and the unknown coexist. I believe that as our exploration deepens, the immunotherapy strategies for breast cancer patients can provide reference experiences for other immunologically cold tumors.
Fei Ma
Director of the Department of Internal Medicine at the Cancer Hospital of the Chinese Academy of Medical Sciences
Yangtze River Scholar Distinguished Professor, Chief Physician, PhD Supervisor
Secretary-General of the National Anti-Cancer Drug Clinical Application Monitoring Committee
Deputy Chairman of the Breast Cancer Committee of the National Cancer Quality Control Center
Secretary-General of the Breast Cancer Screening and Early Diagnosis and Treatment Standards Committee of the National Cancer Center
Expert for the Health China Action Promotion Committee
Vice Chairman of the Oncology Pharmacy Committee of the Chinese Pharmaceutical Association
Vice Chairman of the Integrative Oncology Cardiology Branch of the Chinese Anti-Cancer Association
Vice Chairman of the Multiple Primary and Unknown Primary Tumors Committee of the Chinese Anti-Cancer Association
Secretary-General of the Oncological Drug Clinical Research Committee of the Chinese Anti-Cancer Association
General Secretary of the Geriatric Oncology Branch of the Chinese Geriatrics Society
Editor-in-chief of Cancer Innovation
Recipient of the Second Prize of National Science and Technology Progress Award, and honors such as “Top Ten Outstanding Young Doctors of the Capital” and “Young Scientist Award of China Oncology”
