In surprising setback, combo of Roche’s Tecentriq and chemo fails to help patients with triple-negative breast cancer
Roche broke ground last year when they secured the first FDA approval for a checkpoint therapy in triple-negative breast cancer, a notoriously difficult-to-treat indication that has been passed over by the wave of targeted therapies.
Now, though, doctors are puzzling over why a combination of drugs meant to make that therapy more potent instead appeared to make it less effective.
Roche said Thursday that in a Phase III trial, combining their PD-1/L1 checkpoint therapy Tecentriq with the chemotherapy paclitaxel, did not significantly improve progression-free survival for patients with locally advanced or metastatic triple-negative breast cancer over giving those patients chemotherapy alone. In fact, patients on the Tecentriq-chemo arm had lower overall survival than patients on chemo, although the drugmaker cautioned that the trial was not powered for that endpoint and the data were immature.
The failure is a setback for triple-negative breast cancer patients who, despite new medicines such as Immunomedics’ antibody-drug conjugate Trodelvy, continue to face worse odds and fewer treatment options than other breast cancer patients.
It is also a setback for Roche. Trailing Merck and Bristol Myers Squibb in the checkpoint space, and with AstraZeneca ascendant, the Swiss pharma had hoped to carve a strong niche in triple-negative breast cancer.
Researchers have long combined chemotherapy with newer drugs such as checkpoint inhibitors and targeted agents, so some were surprised that the combo would have little effect. A few doctors debated it on Twitter, with Sherene Loi of the Peter Mac Cancer Centre in Australia offering that the failure may have been a product of the chemotherapy and a steroid patients received before treatment: By lowering white blood cell counts, it could have interfered with the effects of the immunotherapy.
Must the paclitaxel. High dose Dex premed and the neutrophilia it causes can't be good for generating more of and better functioning T cells.
— Dr Sherene Loi (@LoiSher) August 7, 2020
In a statement, Levi Garraway, CMO of Roche’s big biotech sub Genentech, hinted at a similar hypothesis, saying that researchers need to better understand how cancer, the immune system, and the different therapies doctors throw at them all interact.
“Today’s results underscore the need to better understand the cancer and immune system interactions, including the chemotherapy backbone and associated regimens,” he said.