Dive Insight:

It’s taken longer for drugmakers to prove immunotherapy might help patients with breast cancers than those with malignancies of the skin, lung and other organs. Most breast cancer tumors are immunologically “cold” and less susceptible to such drugs. They also tend to spread slowly due, in part, to the availability of other effective medicines.

Triple-negative tumors, which are particularly aggressive and resistant to standard drugs, are an exception. They’re seen as more immunologically “hot,” making it more likely immunotherapy could help. Unlike other types of breast cancer, triple-negative tumors are mainly treated with chemotherapy, so there’s a greater need for new drugs.

Merck and rival Roche, in particular, have sought to prove immunotherapy works in triple-negative breast cancer. Since 2017, both have won approvals of their respective treatments Keytruda and Tecentriq for tumors that have already spread. Both aim to expand with clearances earlier in the course of disease, either before or after surgery.

For later-stage use, Merck and Roche relied on accelerated approvals, using early data that showed effects not yet confirmed to translate to actual clinical benefits. Such a path is typical for cancer immunotherapies, which account for many of the FDA’s speedy drug OKs over the past decade. Faced with criticism, however, the regulator last year responded with an industry-wide review of its decisions, culminating with a three-day meeting last month at which six speedy approvals were evaluated by a panel of outside experts.

Tecentriq’s clearance in triple-negative breast cancer was among the six because follow-up testing failed to show treatment could help patients with advanced disease live longer. The FDA panel voted to overlook that result, however, because of the substantial need for new treatments and promising signals in early studies. (Keytruda, approved in November for late-stage disease, still awaits confirmatory data.)

The FDA and its advisers have signaled the bar may be higher for early cancer. Merck couldn’t win clearance in March based on an improvement in pathological complete responses for Keytruda and chemotherapy over chemotherapy alone. The panel voted, and the FDA agreed, that Merck needed to prove Keytruda could stop cancers from recurring, a statistic known as “event-free” survival that can take time to measure since it relies on disease complications and deaths occurring. Merck noted in a statement Thursday that it took four years for the data to “mature” enough to see a significant difference in EFS.

Merck didn’t disclose the magnitude of the benefit, which will be important to its approval chances. In briefing documents, for instance, FDA scientists flagged more side effects and autoimmune problems in Keytruda-treated patients.

Still, the positive result again puts Merck’s drug in line to be the first of its kind in early-stage breast cancer, as similar measures were used to support approvals of Keytruda and Bristol Myers Squibb’s Opdivo in early skin cancer.

“[W]e look forward to working with the FDA and other global authorities to bring this new option to patients as quickly as possible,” said Roy Baynes, Merck’s chief medical officer and head of global clinical development, in a statement.

Roche’s Tecentriq, administered with chemotherapy, has also improved pathological complete responses in early breast cancer. But Roche hasn’t yet disclosed EFS data or its regulatory plans.