Margaret Gatti-Mays MD, MPH, of the The James Cancer Hospital at Ohio State University, discusses immunotherapy in TNBC.

Immunotherapy Options in TNBC

Margaret Gatti-Mays MD, MPH, of The James Cancer Hospital at Ohio State University, discusses the available immunotherapy options in triple-negative breast cancer.

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Margaret Gatti-Mays MD, MPH, of The James Cancer Hospital at Ohio State University, discusses the available immunotherapy options in triple-negative breast cancer. 

Dissecting Immunotherapy Options for TNBC

Margaret E. Gatti-Mays, MD, MPH, FACP, discusses the current use of neoadjuvant chemoimmunotherapy in early-stage triple-negative breast cancer.

Dr Gatti-Mays on the Use of Neoadjuvant Chemoimmunotherapy in Early-Stage TNBC  

Margaret E. Gatti-Mays, MD, MPH, FACP, section chief, Breast Medical Oncology, associate professor, Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center (OSUCC), OSUCC–James, discusses the current use of neoadjuvant chemoimmunotherapy in early-stage triple–negative breast cancer (TNBC).

In the early breast cancer setting, patients with tumors that are 2 cm or larger, or those with tumors involving the lymph nodes at baseline, are considered candidates for neoadjuvant chemoimmunotherapy, Gatti-Mays begins. The current standard of care, as established by the phase 3 KEYNOTE-522 trial (NCT03036488), supports the use of pembrolizumab (Keytruda) in combination with chemotherapy followed by adjuvant pembrolizumab for patients with early-stage disease, Gatti-Mays details. This randomized, multicenter, double-blind, placebo-controlled trial enrolled 1174 patients with newly diagnosed, previously untreated high-risk early-stage TNBC. Patients were enrolled onto the study regardless of tumor PD-L1 expression.

Initial results from KEYNOTE-522, which were previously reported, primarily focused on the achievement of pathologic complete response (pCR) in TNBC, she continues, adding that pCR is often used as a surrogate endpoint for event-free survival (EFS) in TNBC. The trial demonstrated a pCR rate of 63% (95% CI, 59.5%, 66.4%) among patients receiving pembrolizumab plus chemotherapy, compared with 56% (95% CI, 50.6%, 60.6%) among those receiving chemotherapy alone, Gatti-Mays reports. Additionally, the study reported that fewer patients experienced an event related to EFS in the pembrolizumab plus chemotherapy group compared with the chemotherapy-alone group, at 16% vs 24%, respectively (HR, 0.63; 95% CI, 0.48%-0.82%; 

Based on interim findings from KEYNOTE-522, the FDA approved this neoadjuvant combination in this specified patient population in July 2021. This approval signifies the clinical benefit and improved outcomes associated with adding pembrolizumab to standard chemotherapy in the neoadjuvant setting for patients with early-stage disease, Gatti-Mays concludes.

Margaret E. Gatti-Mays, MD, MPH, FACP, discusses the current use of neoadjuvant chemoimmunotherapy in early-stage triple-negative breast cancer.


Margaret E. Gatti-Mays, MD, MPH, FACP, section chief, Breast Medical Oncology, associate professor, Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center–James, discusses updated biomarker data from the phase 2 NeoPACT trial (NCT03639948) of neoadjuvant chemoimmunotherapy in triple-negative breast cancer (TNBC).

The phase 2, single-arm NeoPACT trial investigated the efficacy of an anthracycline-free regimen of docetaxel and carboplatin combined with pembrolizumab (Keytruda) for patients with stage I, II, or III TNBC, Gatti-Mays begins. The regimen was administered once every 3 weeks for a total of 6 cycles, she details. The study enrolled 120 patients, and 111 were deemed evaluable for a pathologic complete response (pCR). Patients were required to have tumors 1 cm or larger, or positive lymph nodes, Gatti-Mays notes.

Results showed that docetaxel and carboplatin plus pembrolizumab produced a pCR of approximately 58% in the overall population, Gatti-Mays reports. In patients who were node-negative, the pCR was slightly higher at 65%. Moreover, patients with PD-L1 positivity displayed the highest pCR rate of 76%, Gatti-Mays states. The regimen also produced a 2-year disease-free survival (DFS) rate of 89% when evaluating all patients, Gatti-Mays details. In patients who achieved a pCR, the 2-year DFS rate was 98%. After treatment, patients with residual disease achieved a favorable 2-year DFS rate of 78%, Gatti-Mays remarks.

Findings from a subsequent biomarker analysis of NeoPACT were presented at the 2023 ASCO Annual Meeting, Gatti-Mays continues. The analysis delved into specific proliferation signatures and various biomarkers of gene expression, and investigated their ability to predict responses with the neoadjuvant chemoimmunotherapy regimen, she says. Patients in this study were classified as having either low or high stromal tumor-infiltrating lymphocyte (sTIL) levels.

The analysis suggested that these factors could aid in predicting which patients would derive substantial benefits from the chemoimmunotherapy regimen, Gatti-Mays explains. Notably, this prediction holds true even for patients who have sTIL-low TNBC. This discovery contradicts the conventional understanding that higher sTIL levels correlate with better responses with neoadjuvant treatment in breast cancer, Gatti-Mays says.

Proliferation signatures could therefore serve as a predictive tool for identifying patients who may benefit from chemoimmunotherapy, especially in cases with lower sTIL levels, Gatti-Mays emphasizes.

Ultimately, the NeoPACT study not only sheds light on the encouraging efficacy of neoadjuvant chemoimmunotherapy for TNBC, but potentially introduces a more tailored approach to treatment using specific molecular signatures to identify optimal patient populations, Gatti-Mays concludes.

Margaret E. Gatti-Mays, MD, MPH, FACP, discusses updated biomarker data from the phase 2 NeoPACT trial of neoadjuvant chemoimmunotherapy in triple-negative breast cancer.
 


Dr Gatti-Mays on Updated Biomarker Data From the NeoPACT Study in TNBC

Margaret E. Gatti-Mays, MD, MPH, FACP, assistant professor, Division of Medical Oncology, Department of Internal Medicine, Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center–James, discusses considerations for selecting between FDA-approved companion diagnostic assays for measuring PD-L1 expression in triple-negative breast cancer (TNBC).

Currently, the VENTANA PD-L1 (SP142) and the Dako PD-L1 (22C3) assays are approved to aid in the identification of patients with TNBC who are eligible to receive immunotherapy. ​The SP142 assay is approved as a companion diagnostic for atezolizumab (Tecentriq), whereas, the 22C3 assay is approved as a companion diagnostic for pembrolizumab (Keytruda) both in patients with TNBC. The assays evaluate slightly different components of the tumor microenvironment, and they utilize different thresholds for PD-L1 positivity, says Gatti-Mays.

As such, one assay may be preferred in select clinical scenarios vs the other, Gatti-Mays adds. For example, the 22C3 assay could be preferred in patients who are taxane naïve, says Gatti-Mays. Conversely, patients who received a taxane-based regimen, such as weekly paclitaxel, may be better suited to receive the SP142 assay, Gatti-Mays says. In patients who are likely to receive gemcitabine plus carboplatin, the 223C assay may be optimal, Gatti-Mays adds.

Ultimately, utilizing these assays in combination may be reasonable for certain patients, Gatti-Mays explains. However, some institutions may prefer to use the SP142 assay because it has been approved for a longer period, can often be completed in-house, and may yield quicker results compared with the 223C assay, Gatti-Mays concludes.

Margaret E. Gatti-Mays, MD, MPH, FACP, discusses considerations for selecting between FDA-approved companion diagnostic assays for measuring PD-L1 expression in triple-negative breast cancer. 



Margaret E. Gatti-Mays, MD, MPH, FACP

Articles

Dissecting Immunotherapy Options for TNBC

Dr Gatti-Mays on the Use of Neoadjuvant Chemoimmunotherapy in Early-Stage TNBC

Dr Gatti-Mays on Updated Biomarker Data From the NeoPACT Study in TNBC

Dr. Gatti-Mays on Selecting Between FDA-Approved Assays for PD-L1 Expression in Breast Cancer