preface
The 2024 European Society for Medical Oncology Annual Meeting (2024 ESMO) was held in Barcelona, Spain from September 13 to September 17, bringing together scholars from the global oncology field to share the latest research progress in cancer diagnosis and treatment. On the occasion of this meeting, the latest results of the single-arm, prospective phase II clinical trial carried out by the team of Professor Sun Tao of Liaoning Provincial Cancer Hospital were selected for poster presentation at the conference. The study aims to explore the treatment model of the combination of "target, immunization, and chemization" for advanced triple-negative breast cancer (TNBC).
Background:
Triple negative breast cancer is a molecular subtype lacking the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), accounting for about 15%~20% of breast cancer cases. Due to the absence of these receptors, triple-negative breast cancer cannot be treated with conventional hormone therapy or targeted therapies targeting HER2, and treatment options are relatively limited and rely primarily on chemotherapy. As a subtype with a better response to immunotherapy in breast cancer, the therapeutic prospect of immune checkpoint inhibitors (ICIs) combined with chemotherapy has become clear with the publication of clinical research data in recent years. This study is a single-arm, prospective Phase II clinical trial to evaluate the "targeted, immune, chemical" combination of anlotinib (a multi-targeted tyrosine kinase inhibitor [TKI)] in combination with penpulimab (a PD-1 inhibitor) and nab-paclitaxel to explore the therapeutic modality of advanced TNBC.
The 2024 edition of the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Breast Cancer makes a Level I recommendation for the combination of nab-paclitaxel + PD-1 inhibitor in the salvage treatment of advanced TNBC (Category 1A evidence). Penpulimab is an IgG1 subtype monoclonal antibody that acts directly on PD-1 and effectively prevents human PD-1 from binding to its bandands PD-L1 and PD-L2. Penpulimab has a typical antibody structure consisting of 2 heavy chains of the IgG1 isoform and 2 light chains of the κ isoform, covalently linked by disulfide bonds. Amino acid site-directed mutagenesis was carried out on the crystallizable fragment (Fc segment) carried by penpulimab by bioengineering technology, which effectively removed the binding ability to Fcγ receptor I, thereby avoiding the immune cell damage caused by antibody-dependent cell-mediated cytotoxicity (ADCC) and the possible weakening of the anti-tumor effect of PD-1 antibody.
Anlotinib is a small molecule multi-targeted TKI that can effectively inhibit kinases such as VEGFR 1-3, PDGFR α/β, FGFR 1-4, and c-Kit, and has anti-tumor angiogenesis and tumor growth inhibition effects. This reprogramming of the tumor immune microenvironment further lays the theoretical foundation for the synergistic effect of anlotinib combined with immunotherapy. In a phase II, single-arm study, anlotinib alone had an objective response rate (ORR) of 15.38%, a disease control rate (DCR) of 80.77%, and a median progression-free survival (PFS) of 5.22 months in HC-negative breast cancer, with an ORR of 10%, a DCR of 70%, and a median PFS of 4.04 months in HR-negative patients, with mild toxicity and no treatment-related deaths.
Findings:
Based on the above, the investigators conducted a single-arm, prospective phase II clinical trial and chose a three-drug combination regimen based on nab-paclitaxel, the immune checkpoint inhibitor penpulimab and the anti-angiogenic targeted TKI anlotinib to prospectively explore the treatment mode of advanced TNBC. As of March 30, 2024, a total of 33 patients with advanced breast cancer were enrolled. Median follow-up was 6.54 months (95% CI 2.68-11.43). Among the patients who could be evaluated for efficacy (26/33), 1 patient (3.85%) had a complete response (CR); Twenty patients (76.92%) had a partial response (PR), 4 patients (15.38%) had stable disease (SD), and 1 patient (3.85%) had progressive disease (PD). The ORR was 80.77% (95% CI 60.65-93.45) and the DCR was 96.15% (95% CI 80.36-99.90). Median PFS was 11.14 months (95% CI 8.34-18.04), and median overall survival (OS) has not yet been reached. The 6-month OS rate was 95.83% (95% CI 73.92-99.40) and the 12-month OS rate was 80.90% (95% CI 50.05-93.72).
In terms of safety, the most common adverse events (AEs) were grade 1 or 2 according to the Common Adverse Event Evaluation Criteria (CTCAE) version 5.0. Common grade 3 AEs (incidence ≥10%) included neutropenia (33.33%), leukopenia (12.12%), and elevated AST (12.12%). There were two cases of grade 4 neutropenia and one case of grade 4 hypertriglyceridemia. One death (immune-mediated hepatitis) was thought to be related to the PD-1 inhibitor in the trial protocol.
Conclusions of the study
The data from this study phase showed that penpulimab combined with anlotinib and nab-paclitaxel had good efficacy, safety and tolerability in the first-line treatment of advanced TNBC, and the results of the study are expected to provide a new treatment option for the first-line treatment of advanced TNBC.
Expert Profile
Prof. Tao Sun
- Director of the First Department of Breast Medicine, Liaoning Provincial Cancer Hospital, Ph.D. supervisor
- Expert with special allowance from the State Council, second-level professor
- Liaoning Young Famous Doctor
- Member of the Standing Committee of the Breast Cancer Committee of the Chinese Society of Clinical Oncology (CSCO).
- Vice Chairman of the Oncology and Cardiology Committee of the Chinese Society of Clinical Oncology (CSCO).
- Vice Chairman of the Tumor Heterogeneity and Individualized Treatment Committee of the Chinese Anti-Cancer Association
- Vice Chairman of the Tumor Marker Committee of the Chinese Anti-Cancer Association
- Member of the Standing Committee of the Tumor Targeted Therapy Professional Committee of the Chinese Anti-Cancer Association
- Member of the Standing Committee of the Special Committee on Multiple and Unknown Primary Tumors of the Chinese Anti-Cancer Association
- Vice Chairman of the Breast Disease Professional Committee of the China Medical Education Association
- Vice Chairman of the MDT Committee on Precision Medicine and Oncology of China Research Hospitals
- Chairman of the Tumor Marker Committee of Liaoning Anti-Cancer Association
- Chairman of the Chemotherapy Committee of Liaoning Anti-Cancer Association (Elect).
- Chairman of the Antitumor Drug Professional Committee of Liaoning Pharmaceutical Association
- Vice Chairman of Liaoning Provincial Pharmaceutical Drug Clinical Evaluation Research Professional Committee
Bibliography:
Tao Sun, et al. 2024 ESMO 387P.
Editor: Prof. Tao Sun
Reviewer: Ryland
Typography: Ryland
Executive: Babel
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