First results from a phase II study evaluating atezolizumab plus carboplatin presented at the ESMO Breast Cancer Virtual Congress 2021, held 5 to 8 May, demonstrated clinical benefit in patients with metastatic invasive lobular breast cancer (ILC), particularly in patients with triple negative ILC.
According to Leonie Voorwerk, PhD student in the Division of Tumour Biology & Immunology, Netherlands Cancer Institute in Amsterdam, Netherlands, endocrine treatment is usually an effective treatment for metastatic ILC but there are limited options for successful successive therapies.
She emphasised that ILC appears to be a different disease entity than invasive breast cancer of no special type. In addition, translational data suggested that a subgroup of ILC has high expression of immune-related genes and preclinical data indicated that this ILC subtype may be responsive to immune checkpoint blockade in combination with platinum. Therefore, this investigation of atezolizumab administered after immune induction with carboplatin in patients with metastatic ILC was designed.
The single-arm, multicentre phase II GELATO study (NCT03147040) enrolled patients with metastatic ILC who received 12 weekly cycles of carboplatin at AUC 1.5. Atezolizumab was administered at 1200 mg every 3 weeks beginning with the third cycle of carboplatin and continued until progression or intolerability. The GELATO had a Simon’s two-stage design, which required 22 patients to receive at least 1 cycle of atezolizumab in the first stage; of these, at least 3 patients had to be free of progression after 24 weeks to warrant further investigation in the second stage.
All patients had received a maximum of 2 lines of prior palliative chemotherapy and those with oestrogen receptor positive tumours were endocrine treatment refractory.
Progression-free survival at 24 weeks according to RECIST v1.1 served as the primary endpoint.
Patients showed clinical benefit including those with triple negative ILC
Of the 23 evaluable patients receiving atezolizumab in the first stage, at least 4 patients were free of progression at 24 weeks, thus the primary endpoint of the first stage of the study was met. Among these 4 patients, one had an ongoing response.
Swimmersplot of all patients included in the first stage of the GELATO-trial. 4 patients were free of progression after 6 months, as indicated by the dashed line.
© Leonie Voorwerk.
Two patients have started treatment but have not yet reached an endpoint, leaving 21 patients available for best overall response assesment. In this cohort, 4 patients achieved a partial response providing an objective response rate of 19%. Furthermore, 2 patients showed stable disease of at least 6 months, for a clinical benefit rate of 29%.
Overall, out of the 6 patients with clinical benefit, 4 patients had triple-negative ILC.
The investigators found no association between clinical benefit and stromal tumour-infiltrating lymphocytes or stromal CD8+ counts. There was a trend towards higher PD-L1 expression in patients with clinical benefit, with out of the 5 patients with PD-L1 positive tumours 3 patients having clinical benefit.
Sylvia Adams of the NYU Langone Health in New York City, NY, US who discussed the study findings said that the study population was clinically heterogenous. In terms of predictive biomarkers, she said that most responses in patients with triple-negative ILC, stromal tumour-infiltrating lymphocytes and CD8+ counts at baseline are not associated with clinical benefit; there is a trend towards higher PD-L1 expression in responding patients, while serial biopsy results are pending. Further translational research should assess if responses are associated with reported immune-related subtype of ILC and/or high tumour mutational burden. Contribution of either agent to responses is unknown as single arm. She questioned if anti-CTLA4 blockade could improve response rates and durability.
Conclusions
The investigators pointed out that GELATO represents the first clinical immunotherapy study executed exclusively in metastatic ILC. They noted that they showed a clear efficacy signal of PD-L1-blockade in combination with carboplatin in patients with metastatic ILC, mainly in patients with triple negative ILC.
The study was funded by Hoffmann-La Roche.
Reference
LBA3 – Voorwerk L, Horlings H, Van Dongen M, et al. Atezolizumab with carboplatin as immune induction in metastatic lobular breast cancer: first results of the GELATO-trial. ESMO Breast Cancer Virtual Congress 2021 (5-8 May).