Invasive lobular breast cancer (ILC) is a special histological breast cancer subtype for which endocrine treatment is effective, but options thereafter are limited. ILC appears to be a different disease entity than invasive breast cancer of no special type. Translational data suggested that a subgroup of ILC has high expression of immune-related genes. Preclinical data revealed that this subtype may be responsive to combined platinum and immune checkpoint blockade. Here we present the first results of a single-arm phase II trial of atezolizumab (atezo) after immune induction with carboplatin in metastatic (m)ILC.
In the single-arm, multicenter GELATO-trial (NCT03147040), patients with mILC were treated with 12 cycles of carboplatin q1w (AUC 1.5 mg/mL·min) and atezo (1200 mg) q3w starting from the third cycle of carboplatin and continuing until progression or intolerability. Patients had received a maximum of 2 lines of palliative chemotherapy and were endocrine refractory in case of ER-positive tumors. The primary endpoint was progression-free survival at 24 weeks according to RECIST1.1. Following a Simon’s two-stage design, 22 patients, receiving at least 1 cycle of atezo, needed to be included in the first stage, of whom at least 3 patients had to be free of progression after 24 weeks to warrant further investigation in the second stage.
Among 23 included evaluable patients, 4 patients were free of progression at 24 weeks, meeting the primary endpoint of the first stage of the trial. 1 patient has an ongoing response and 2 patients have started treatment but have not yet reached an endpoint. 4 out of these 21 patients had a partial response resulting in an objective response rate of 19% and 2 patients had stable disease, resulting in a clinical benefit rate of 29%. 4 of the patients with clinical benefit had triple negative (TN)-ILC, whereas in total 5 out of 23 patients had TN-ILC. Stromal tumor-infiltrating lymphocytes were not associated with clinical benefit. PD-L1 and CD8 will be presented at the meeting.
This is the first clinical immunotherapy trial executed exclusively in mILC. We show a clear efficacy signal of PDL1-blockade in combination with carboplatin in mILC, mainly in patients with TN-ILC.
NCT03147040.
Netherlands Cancer Institute.
Roche.
H. Horlings: Advisory/Consultancy: SlideScore.com; Advisory/Consultancy: Ellogen.ai. R.F. Salgado: Research grant/Funding (institution): Breast Cancer Research Foundation. G.S. Sonke: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche. K. de Visser: Research grant/Funding (institution): Roche; Advisory/Consultancy: Third Rock Ventures. T.N. Schumacher: Advisory/Consultancy: Adaptive Biotechnologies; Advisory/Consultancy, Shareholder/Stockholder/Stock options: AIMM Therapeutics; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Allogene Therapeutics; Advisory/Consultancy: Amgen; Advisory/Consultancy: Merus; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Neon Therapeutics; Advisory/Consultancy: Scenic Biotech; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Bristol-Myers-Squibb; Research grant/Funding (institution): Merck KGaA. C.U. Blank: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers-Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy: Pfizer; Advisory/Consultancy: GSK; Advisory/Consultancy: GenMab; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Third Rock Venture; Research grant/Funding (institution): NanoString Technologies; Shareholder/Stockholder/Stock options: Immagene B.V. C.P. Schroder: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): SNS Oncology; Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Synthon; Research grant/Funding (institution): CytoMx Therapeutics. V. Tjan-Heijnen: Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Honoraria (institution), Research grant/Funding (institution): Roche; Research grant/Funding (institution): Eisai; Honoraria (institution), Research grant/Funding (institution): E. Lilly. S.C. Linn: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Eurocept- Pharmaceuticals; Advisory/Consultancy: Cergentis; Advisory/Consultancy: IBM; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Immunomedics. M. Kok: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers-Squib; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): AstraZeneca.