Abstract PO2-06-06: Effectiveness and prognostic predictors of primary systemic therapy for de-novo Stage IV breast cancer - Supplementary analysis of JCOG1017 PRIM-BC

Abstract Background The optimal choice of drug is important in treating metastatic breast cancer, and the efficacy of the drug should be determined early, especially in cases of progression. On the other hand, untreated de novo Stage IV (dnST-IV) patients are expected to be more sensitive to drugs, but no detailed data are available. In JCOG1017 (Randomized trial of primary tumor resection in dnST-IV), dnST-IV patients were treated with primary systemic therapy for 3 months according to breast cancer subtypes before randomization. We already presented the results of primary endpoint. Primary tumor resection (PTR) could not significantly prolong the overall survival of de-novo stage IV breast cancer patients with sensitivity to primary systemic therapy. We conducted the supplementary analysis of JCOG1017 to clarify the efficacy of primary systemic therapy for dnST-IV and develop optimal treatment strategies for dnST-IV breast cancer. Methods In JCOG1017, systemic therapy was performed for each subtype/metastatic status as follows; 1) hormone therapy: ER+ HER2- and no life-threatening metastases, 2) weekly PTX therapy: life-threatening metastases, or ER-HER2-, 3) trastuzumab + pertuzumab + docetaxel (HPD) therapy OR trastuzumab + paclitaxel (HPTX) therapy: ER-HER2+. 4) hormone therapy: ER+HER2+ and no life-threatening metastases. The non-PD rate (no increase of more than 10% of the sum of the diameters of the target lesions compared before systemic therapy), the responses rate (cCR or cPR), and overall survival (OS) of responder (cCR or cPR)/non-responder (cSD or cPD) and PD/non-PD were examined. Results Among 569 patients who received primary systemic therapy in JCOG 1017, the non-PD rate was 77.2% and the response rate was 29.0% after 3 months of systemic therapy. By subtype, the non-PD rate was 78.2% for ER-HER2-, 75.4% for ER+HER2-, 92.9% for ER-HER2+, and 66.7% for ER+HER2+. The response rate was 36.4% for ER-HER2-, 13.4% for ER+HER2-, 81.0% for ER-HER2+, and 40.3% for ER+HER2+. In multivariable analysis, the non-PD rate was higher in postmenopausal (odds ratio [OR] 1.673, p=0.0240) and PgR-positive (OR 2.391, p= 0.0019) patients besides subtypes. Analysis results by drug were as follows; 1) hormone therapy (non-PD rate: 72.9%) was more effective for PgR-positive (OR 3.258, p< 0.0001), less effective for patients with visceral metastasis (OR 0.605, p=0.0334) and HER2-positive (OR 0.365, p=0.0016), 2) wPTX (non-PD rate: 76.1%) was no significant predictors of efficacy, 3) HPD/HPTX (non-PD rate: 92.7%) was more effective in patients with visceral metastasis (OR 15.818, p=0.0030). PD patients had much worse OS (hazard ratio [HR] 0.501, p< 0.0001) compared to non-PD, whereas responders had a little worse OS (HR 0.788, p=0.0538) compared to non-responders. Similar tendency was observed in any drug. Discussion Predictors of response to primary systemic therapy differed by subtype, with the need for treatment strategies tailored to PgR, HER2 expression, and the status of visceral metastasis. In the ER+HER2+ group, the efficacy of hormonal therapy alone was low, and combination therapy with molecular-targeted agents was considered necessary. The non-PD rate reflected prognosis in determining the efficacy of primary systemic therapy for dnST-IV. Citation Format: Tadahiko Shien, Akihiko Shimomura, Makoto Ishitobi, Kiyo Tanaka, Takahiro Tsukioki, Takashi Yamanaka, Fumitaka Hara, Kenjiro Aogi, Yasuhiro Yanagita, Michiko Tsuneizumi, Naohito Yamamoto, Hiroshi Matsumoto, Akihiko Suto, Ken-ichi Watanabe, Michiko Harao, Chizuko Kanbayashi, Mitsuya Ito, Keisei Anan, Shigeto Maeda, Keita Sasaki, Gakuto Ogawa, Haruhiko Fukuda, Hiroji Iwata. Effectiveness and prognostic predictors of primary systemic therapy for de-novo Stage IV breast cancer - Supplementary analysis of JCOG1017 PRIM-BC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-06-06.