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Experts Debate Readiness of Immunotherapy for Early TNBC

At the virtual 2021 Great Debates and Updates in Women’s Oncology meeting, Heather L. McArthur, MD, MPH, Cedars-Sinai Medical Center, Los Angeles, California, engaged in a lively debate regarding immunotherapy for early triple-negative breast cancer (TNBC).

While her opponent, Javier Cortes, International Breast Cancer Center, Barcelona, Spain, believes immunotherapy for TNBC is ready for prime-time, Dr McArthur argues otherwise. 

Dr Cortes stated that immunotherapy was linked to a significant increase in event-free survival (EFS) among patients with TNBC, HER2-positive, and HR-positive/HER-negative, breast cancer, but Dr McArthur dismissed it. 

“The data that we are missing is the event-free survival benefit. Where is the proof that this improvement in pathologic complete response will actually translate into improved curates for our patients?,” she questioned.

Moving onto the KEYNOTE522 study, patients receiving pembrolizumab plus chemotherapy had a pathologic complete response rate (pCR) 14% greater than those in the placebo group - regardless of PD-L1 status. However, when this data was updated for the FDA ODAC review, it dropped from 14% to 9.2%. By the third interim analyses, it was down to 7.5%

After a 15 and a half month follow-up, the EFS data was presented as 6% higher in the pembrolizumab group than the placebo group. Although, at the median 26.1-month follow-up, the EFS rate looked to be sustained at about 7%, there was broad variability in the probability of these pCR’s predicting EFS success in future analyses. The FDA’s model showed variability of 62%-78%, while the applicants model was 32%-92%.

Furthermore, as Dr McArthur states, there are increased toxicities when adding immunotherapy to chemotherapy. Immune-related adverse events (irAES) were higher in the pembrolizumab group than the placebo, with 15% experiencing AE’s of grade 3 or higher and 10% being hospitalized, compared to 2% and 1% in the placebo group, respectively.

Of the 782 patients in the pembrolizumab arm, 15% reported hypothyroidism, 6% reported severe skin reactions, and 3% reported adrenal insufficiency, compared to 6%, 1%, and 0 in the placebo group, respectively.

“Further follow-up is required to better understand the true benefit for our patients. In the interim, until that data is available we have to acknowledge that there is real toxicity with these agents,” added Dr McArthur.

“In the absence of definitive evidence that we are improving cure rates, and in the absence of reliable predictive biomarkers, that predict for both benefit and toxicity, a risk-venefit calculation is not currently possible and thus immunotherapy is not ready for prime-time for patients with early stage triple-negative breast cancer,” she concluded.Alexandra Graziano

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