Weighing Risks of Using Neoadjuvant Immunotherapy in TNBC

Lee Schwartzberg, MD, discusses the concerns of treating patients with early triple-negative breast cancer with immunotherapy.

Lee Schwartzberg, MD, chief medical director of West Cancer Center and chief of the division of hematology/oncology at the University of Tennessee Health Science Center, discusses the concerns of treating patients with early triple-negative breast cancer (TNBC) with immunotherapy.

The phase 3 KEYNOTE-522 (NCT03036488) trial of pembrolizumab (Keytruda) showed superior pathological complete response and event-free survival for patients who received pembrolizumab plus paclitaxel and carboplatin versus paclitaxel and carboplatin chemotherapy alone in the neoadjuvant and adjuvant setting.

Schwartzberg says that while pembrolizumab can decrease the rate of relapse, some patients may be cured of TNBC with standard chemotherapy and surgery, so it is challenging to decide which patients do not need immunotherapy.

In the pembrolizumab arm of the study, 13.7% of patients had hypothyroidism and 4.6% had hyperthyroidism versus 3.3% and 1.0%, respectively, in the chemotherapy arm. Severe skin reaction and adrenal insufficiency were also observed in a small number of patients who received pembrolizumab. According to Schwartzberg, these are believed to be long-term adverse events and physicians must weigh them against the potential benefit of pembrolizumab in preventing disease relapse, which may be incurable.


0:08 | There is some cost to adding pembrolizumab in the adjuvant setting. Remember that many of these patients would be cured by standard therapy. We don't know which ones those are. We also know there's a substantial relapse rate, so we're trying to improve that relapse rate and reduce it. But we have to acknowledge that we're treating patients [who], with standard therapy, would be cured and the toxicity is evenly distributed among all patients. So we have to manage the risk-benefit ratio.

The biggest issue with pembrolizumab in the neoadjuvant/adjuvant setting is obviously immune effects, and most commonly effects on the thyroid. So about 20% of patients get either hypothyroid, [more] commonly, or hyperthyroid. We think that that's most likely going to be long standing. So we have to weigh the benefit of treating patients and trying to prevent their cancer coming back, at which point it's typically not curable, versus long-term effects on the thyroid gland, or in rare cases, on the adrenal gland or on the skin.

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