163MO - Randomized phase II study of eribulin-based neoadjuvant chemotherapy for triple-negative primary breast cancer patients stratified by homologous recombination deficiency status (JBCRG-22)

Background

Eribulin mesylate (Eri) improves survival in patients with metastatic triple negative breast cancer (TNBC) and its toxicity profile differs from that of taxanes or anthracyclines-based regimen (A). We explored Eri-based neoadjuvant regimens for primary TNBC patients stratified by homologous recombination deficiency (HRD) and BRCA1/2 germline status in a prospective randomized phase II study.

Methods

The study enrolled patients with cT1c–T3(<=7 cm), cN0–N1, and M0, TNBC. Patients <65 years old (yo) with HRD+ or BRCA1/2 variant+ cancer were allocated to group A1 (4 cycles of weekly paclitaxel [wP] + carboplatin [Cb] then 4 of A) or A2 (4 cycles of Eri + Cb then 4 of A). Patients >=65 yo, or <65 yo with HRD- were allocated to group B1 (6 cycles of Eri + cyclophosphamide) or B2 (6 cycles of Eri + capecitabine), each with 4 cycles of A for non-responders to the first 4 cycles of Eri-based therapy. Age, tumor size, nodal status and Ki67-LI were stratification factors. Primary endpoint was pCR rate (ypT0-is, ypN0; centrally confirmed). Secondary endpoints were safety, ORR and breast conservation rate (BCR).

Results

The full analysis set comprised data from all 99 patients enrolled (2/2017-1/2019). Characteristics were similar across groups. In B1 and B2, 48.1% and 55.6%, respectively, completed 6 cycles of an Eri-based regimen. The pCR rates in A1, A2, B1and B2 were 65.2%, 45.5%, 18.5% and 18.5%, respectively (Table). No major difference was seen in secondary endpoints, but peripheral neuropathy incidence was 73.9% in A1 versus 31.8%, 22.2%, 25.9% in A2, B1, B2, respectively. Table: 163MO

Patient characteristics and response

* Median (range)

Conclusions

In TNBC patients with HRD+ or BRCA1/2 variant+ (<65 yo), pCR rate was 65% for wP+Cb followed by A and 46% for Eri+Cb followed by A. Neurotoxicity was less frequent with Eri-based regimens, which are feasible in this neoadjuvant setting. Biomarker studies are on-going.

Clinical trial identification

UMIN-CTR: UMIN000023162.

Editorial acknowledgement

Legal entity responsible for the study

Japan Breast Cancer Research Group.

Funding

Japan Breast Cancer Research Group and Eisai Co., Ltd.

Disclosure

H. Bando: Honoraria (self), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Eisai; Honoraria (self), Outside the submitted work: Kyowa Kirin; Honoraria (self), Outside the submitted work: Taiho; Honoraria (self), Outside the submitted work: Chugai; Honoraria (self), Outside the submitted work: Nihon Kayaku; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Novartis. N. Masuda: Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Chugai; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: AstraZeneca; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Pfizer; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Eli Lilly; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Eisai; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Takeda; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Kyowa Kirin; Research grant/Funding (institution), Outside the submitted work: MSD; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Novartis; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Daiichi Sankyo; Advisory/Consultancy, Board of directors: Japan Breast Cancer Research Group Association. T. Yamanaka: Honoraria (self), Outside the submitted work: Eisai; Honoraria (self), Outside the submitted work: Novartis; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: Kyowa Kirin; Honoraria (self), Outside the submitted work: Chugai; Honoraria (self), Outside the submitted work: Daiichi Sankyo. M. Takahashi: Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: Pfizer. S. Nagai: Honoraria (self), Outside the submitted work: Chugai; Honoraria (self), Outside the submitted work: Taiho ; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: Novartis; Honoraria (self), Outside the submitted work: Eisai. S. Ohtani: Honoraria (self), Outside the submitted work: Chugai; Honoraria (self), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: Eisai. T. Aruga: Honoraria (self), Outside the submitted work: Eisai. Y. Kikawa: Honoraria (self), Outside the submitted work: Eisai; Honoraria (self), Outside the submitted work: Novartis; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: Taiho; Honoraria (self), Outside the submitted work: Chugai. H. Kasai: Research grant/Funding (institution): Eisai; Honoraria (self), Outside the submitted work: Chugai. H. Kawabata: Research grant/Funding (institution): Chugai; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Daiichi Sankyo. S. Morita: Honoraria (self), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Bristol-Myers Squibb Company; Honoraria (self), Outside the submitted work: Chugai; Honoraria (self), Outside the submitted work: Eisai; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: MSD; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Taiho. R. Uozumi: Honoraria (self), Outside the submitted work: Eisai; Honoraria (self), Outside the submitted work: Sawai; Honoraria (self), Outside the submitted work: CAC Croit.

S. Ohno: Honoraria (self), Outside the submitted work: Chugai; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Eisai; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Taiho; Honoraria (self), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: Kyowa Kirin; Honoraria (self), Outside the submitted work: Nihon Kayaku. M. Toi: Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Chugai; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Takeda; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted work: Kyowa Kirin; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Taiho; Research grant/Funding (institution), Outside the submitted work: JBCRG association; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted work: Daiichi Sankyo; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: AstraZeneca; Honoraria (self), Outside the submitted work: Eli Lilly; Honoraria (self), Outside the submitted work: MSD; Honoraria (self), Outside the submitted work: Genomic Health; Honoraria (self), Outside the submitted work: Novartis; Honoraria (self), Outside the submitted work: Konica Minolta; Research grant/Funding (institution), Outside the submitted work: Astellas; Honoraria (self), Outside the submitted work: Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Shimadzu; Honoraria (self), Outside the submitted work: Yakult; Honoraria (self), Research grant/Funding (institution), Outside the submitted work: Nihon Kayaku; Research grant/Funding (institution), Outside the submitted work: AFI Technologies; Advisory/Consultancy, Outside the submitted work: Athenex Oncology; Advisory/Consultancy, Board of directors: JBCRG association,; Advisory/Consultancy, Board of directors: Organisation for Oncology and Translational Research; Advisory/Consultancy, Board of directors: Kyoto Breast Cancer Research Network. All other authors have declared no conflicts of interest.