- The Food and Drug Administration has made Merck & Co.'s Keytruda the first immunotherapy available for patients with a form of early-stage breast cancer, reversing an earlier decision to reject the treatment now that the drugmaker has accrued new data to support its use.
- The agency approved a regimen of Keytruda and chemotherapy starting before surgery to remove a tumor in triple-negative breast cancer patients and followed by immunotherapy alone afterwards. Merck recently showed treatment led to a 37% reduction in risk of cancer's return or death compared to chemotherapy alone.
- Merck's trial hasn't run long enough to definitively determine whether the Keytruda-chemo regimen can extend patients' lives. Nonetheless, the results served as confirmatory evidence for the drug's use in metastatic triple-negative disease, leading the FDA to convert Keytruda's accelerated nod in that indication to a full approval.
The approval caps an unusually fast turnaround for Merck, which, in five months, gathered enough data to reverse a regulatory rejection, stayed ahead of its main rival, and may now change how an aggressive type of breast cancer is treated.
Merck and Roche have been more active than their peers in testing immunotherapies against breast cancer — specifically, the fast-moving triple-negative form that appears more immunologically "hot" and thus susceptible to treatment with their drugs. Since 2017, the FDA has cleared Keytruda and Roche's Tecentriq for triple-negative tumors that have already spread. Both companies have worked to expand those clearances earlier in the course of the disease, before and after surgery.
For later-stage use, Merck and Roche relied on accelerated approvals based on early data showing effects not yet confirmed to translate to actual clinical benefits. That path has been common for immunotherapies, but has increasingly led to criticism of the FDA, spurring the regulator last year to begin an industry-wide review of its accelerated approval decisions. Since then, Merck, Roche, Bristol Myers Squibb and AstraZeneca have each withdrawn approvals in stomach, liver and other cancers.
Merck and Roche's breast cancer approvals have come under increased scrutiny as well. Roche, for instance, failed to prove Tecentriq could help triple-negative patients with advanced disease live longer, putting the drug's use in breast cancer in jeopardy. In Merck's case, the FDA stonewalled the company's attempt to win clearance of Keytruda in early-stage disease based on pathological complete responses, or the disappearance of cancers from tissue samples, and asked for more data.
Roche appears to have held onto its approval after an FDA panel voted to overlook the negative result at a hearing in April. But the Swiss company has now been surpassed by Merck. On July 15, the drugmaker detailed the results regulators were looking for, showing Keytruda and chemotherapy could help stave off the return of cancer — a finding the study's lead investigator, in an interview, called a "milestone" for patients with triple-negative breast cancer, even despite the increased risk of the immune-mediated complications associated with immunotherapy.
"I personally struggle to see how one wouldn't discuss this treatment option with a patient," said the investigator, Peter Schmid, the chair of cancer medicine at Barts Cancer Institute at Queen Mary University London. The data show "we have a new standard of care going forward," he said earlier this month.
The FDA acted swiftly, approving Keytruda less than two weeks after Merck's presentation and using that result to confirm the drug's benefit in more advanced disease.
Incidentally, the FDA's decision wasn't based on new findings Merck also reported Tuesday from the study that underlied its accelerated approval in late-stage triple-negative breast cancer: Trial participants treated with Keytruda lived longer than those who received chemotherapy, though Merck didn't provide specifics.