Tecentriq Plus Carboplatin Demonstrates Clinical Activity in Metastatic Invasive Lobular Breast Cancer, Particularly in Triple-Negative Subtype

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Recently, at the 2021 ESMO Breast Cancer Online Congress, results from a Phase II clinical study sponsored by Roche showed that the anti-PD-L1 therapy Tecentriq (atezolizumab) in combination with carboplatin demonstrated clinical benefit in patients with metastatic invasive lobular carcinoma (ILC), particularly those with triple-negative ILC.

Dr. Leonie Voorwerk, a researcher from the Department of Tumor Biology and Immunology at the Netherlands Cancer Institute, pointed out that endocrine therapy is usually an effective treatment for metastatic invasive lobular carcinoma (ILC), but there are limited successful subsequent treatment options. Dr. Leonie Voorwerk emphasized that ILC appears to be a distinct disease entity rather than a special type of invasive breast cancer. Furthermore, translational research data indicate that a subtype of ILC exhibits high expression of immune-related genes. Preclinical data suggest that this subtype of ILC may respond therapeutically to combination treatment with immune checkpoint inhibitors and platinum-based drugs.

Therefore, the study presented at this conference aims to evaluate Tecentriq treatment following carboplatin immune induction in patients with metastatic invasive lobular carcinoma (ILC). In this single-arm, multicenter, Phase II GELATO study (NCT03147040), patients with metastatic ILC received 12 weekly cycles of carboplatin (dose AUC 1.5), with Tecentriq administered once every three weeks starting from the third cycle of carboplatin therapy and continuing until disease progression or unacceptable toxicity. The study employed a Simon two-stage design, requiring 22 patients to receive at least one cycle of Tecentriq in the first stage; among these, at least three patients needed to be progression-free at 24 weeks to warrant further investigation in the second stage.

All patients had received up to two lines of palliative chemotherapy, and all patients with estrogen receptor–positive disease were refractory to endocrine therapy. The primary endpoint of the study was progression-free survival (PFS) at week 24.

In the first stage, among the 23 evaluable patients treated with Tecentriq, at least 4 patients had no progression at 24 weeks, thus meeting the primary endpoint of the first stage. Among these 23 patients, a total of 21 patients were available for best overall response assessment, while the other 2 patients had initiated treatment but had not reached 24 weeks.

Data showed that 4 patients achieved partial response (PR) in this cohort, with an objective response rate (ORR) of 19% (4/21). In addition, 2 patients had stable disease for at least 6 months. The clinical benefit rate was 29% (6/21).

Overall, among the 6 patients who achieved clinical benefit, 4 had triple-negative invasive lobular carcinoma (ILC). The researchers found no association between clinical benefit and either stromal tumor-infiltrating lymphocytes or stromal CD8+ counts. In patients with clinical benefit, there was a trend toward higher PD-L1 expression; 3 out of 5 patients with PD-L1-positive tumors achieved clinical benefit.

Dr. Sylvia Adams of NYU Langone Health participated in the discussion of the results. She pointed out that the study population was clinically heterogeneous. In terms of predictive biomarkers, the highest rate of clinical response was observed in patients with triple-negative invasive lobular carcinoma (ILC). Baseline stromal tumor-infiltrating lymphocytes and CD8+ counts were not associated with clinical benefit. Among responders, there was a trend toward increased PD-L1 expression, although results from serial biopsies are not yet available. Further translational studies are needed to assess whether response is associated with reported immune-related ILC subtypes and/or high tumor mutational burden. Additionally, in this single-arm study, the contribution of any individual drug to the response remains unknown.

Researchers noted that GELATO is the first clinical immunotherapy study specifically targeting metastatic invasive lobular carcinoma (ILC). The study results demonstrated clear efficacy signals for Tecentriq in combination with carboplatin in patients with metastatic ILC, predominantly those with triple-negative ILC.

Reference Source: Atezolizumab with Carboplatin as Immune Induction Shows Promise in Metastatic Lobular Breast Cancer