First results from the phase II GELATO study evaluating atezolizumab plus carboplatin presented at the ESMO Breast Cancer Virtual Congress 2021 demonstrated clinical benefit in patients with metastatic invasive lobular breast cancer, particularly in patients with triple-negative invasive lobular breast cancer (Abstract LBA3).
More About Invasive Lobular Breast Cancer
According to presenting author Leonie Voorwerk, a PhD student in the Division of Tumor Biology & Immunology at the Netherlands Cancer Institute, endocrine treatment is usually an effective treatment for metastatic invasive lobular breast cancer, but there are limited options for successful successive therapies.
Leonie Voorwerk
She emphasized that invasive lobular breast cancer appears to be a different disease entity than invasive breast cancer of no special type. In addition, translational data suggested that a subgroup of patients with invasive lobular breast cancer has high expression of immune-related genes; preclinical data indicated that this invasive lobular breast cancer 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 invasive lobular breast cancer was designed.
GELATO Trial
The single-arm, multicenter phase II GELATO study (ClinicalTrials.gov identifier NCT03147040) enrolled patients with metastatic invasive lobular breast cancer who received 12 weekly cycles of carboplatin at area under the curve = 1.5. Atezolizumab was administered at 1,200 mg every 3 weeks beginning with the third cycle of carboplatin and continued until disease progression or intolerability. GELATO had a Simon’s two-stage design, which required 22 patients to receive at least one cycle of atezolizumab in the first stage; of these, at least three patients had to be free of disease progression after 24 weeks to warrant further investigation in the second stage.
All patients had received a maximum of two lines of prior palliative chemotherapy, and those with estrogen receptor–positive tumors were endocrine treatment–refractory.
The primary endpoint was progression-free survival at 24 weeks according to Response Evaluation Criteria in Solid Tumors version 1.1.
Clinical Benefit Demonstrated
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 four patients, one had an ongoing response.
Two patients have started treatment but have not yet reached an endpoint, leaving 21 patients available for best overall response assessment. In this cohort, four patients achieved a partial response, providing an objective response rate of 19%. Furthermore, two patients showed stable disease of at least 6 months, for a clinical benefit rate of 29%.
Overall, out of the six patients with clinical benefit, four patients had triple-negative invasive lobular breast cancer.
The investigators found no association between clinical benefit and stromal tumor–infiltrating lymphocytes or stromal CD8+ counts. There was a trend toward higher PD-L1 expression in patients with clinical benefit, with three patients with PD-L1–positive tumors exhibiting clinical benefit out of five PD-L1–positive patients total.
The investigators pointed out that GELATO represents the first clinical immunotherapy study executed exclusively in metastatic invasive lobular breast cancer. They noted that they showed a clear efficacy signal of PD-L1 blockade in combination with carboplatin in patients with metastatic invasive lobular breast cancer, mainly in patients with triple-negative invasive lobular breast cancer.
Commentary
Sylvia Adams, MD
Sylvia Adams, MD, of NYU Langone Health, discussed the study findings. She said that the study population was clinically heterogeneous. In terms of predictive biomarkers, she said that most responses in patients with triple-negative invasive lobular breast cancer, stromal tumor–infiltrating lymphocytes, and CD8+ counts at baseline are not associated with clinical benefit; there is a trend toward 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 invasive lobular breast cancer and/or high tumor mutational burden. Contribution of either agent to responses is unknown as single arm. She questioned if anti–CTLA-4 blockade could improve response rates and durability.
Disclosure: The study was funded by Hoffmann-La Roche. For full disclosures of the study authors, visit oncologypro.esmo.org.
