With Roche’s Tecentriq out of the picture, Merck’s Keytruda is now detailing key data that prove why it deserves a place in newly diagnosed metastatic triple-negative breast cancer.
Keytruda, used in tandem with chemotherapy, cut the risk of death by 27% over chemo alone in previously untreated patients whose tumors expressed the PD-L1 biomarker at a combined positive score (CPS) of at least 10.
Adding Keytruda helped those patients live an additional 6.9 months, or a median of 23 months, according to data unveiled at the European Society for Medical Oncology 20201 annual meeting.
Keytruda snagged an accelerated approval in front-line triple-negative breast cancer in November based on results showing it could stave off tumor progression. An FDA green light in July for its use around surgery for early-stage, high-risk TNBC converted that conditional nod into a full one.
Just as it failed to move the needle on cancer progression among patients with PD-L1 scores of at least 1—a broader group of patients—Keytruda also failed to show a statistically significant survival benefit in that population. Adding Keytruda only pared down the risk of death by 14% in patients whose PD-L1 scores came in at 1 or above. The median survival time was 7.6 months for the Keytruda-chemo group and 5.6 months for the solo chemo group.
Keytruda’s latest win, from the Keynote-355 trial, came as Roche made the surprising move to pull Tecentriq’s front-line TNBC indication off its label—even after an FDA advisory committee voted in April to keep that conditional nod in place.
Tecentriq, used in combination with Bristol Myers Squibb’s chemo drug Abraxane (nab-paclitaxel), was the first immuno-oncology agent to pick up an FDA nod in TNBC. But Tecentriq flopped a later trial alongside the original paclitaxel formulation, throwing doubt on that use, and prompting a close inspection of that data during the FDA advisory panel meeting.
Keytruda likely played a part in forcing Tecentriq out of the TNBC field. In taking back Tecentriq’s indication in late August, Roche said that “due to the recent changes in the treatment landscape, the FDA no longer considers it appropriate to maintain the accelerated approval.”
In July, Merck revealed that Keytruda, used both before and after surgery, reduced the risk of disease worsening, cancer returning or death by 37% in patients with early-stage, nonmetastatic TNBC. And just as Merck successfully convinced the FDA to reverse a previous rejection of that neoadjuvant and adjuvant indication, the Keynote-355 trial also reported the now-detailed positive overall survival readout.
With Tecentriq out of the way, Keytruda can have the TNBC immuno-oncology market all to itself for awhile. But as Roche’s chief medical officer Levi Garraway made clear in an earlier statement about the withdrawal, the Swiss drugmaker will continue to study Tecentriq in metastatic TNBC. For example, the ongoing IMpassion132 trial is testing the PD-L1 inhibitor alongside chemo for patients with early relapsing TNBC.
Merck is committed to continuing to evaluate promising novel therapies in TNBC, Vicki Goodman, vice president of oncology clinical research at Merck Research Laboratories, said in an interview.
Goodman highlighted the New Jersey pharma’s recent tie-up with Seagen on the latter’s LIV-1 antibody-drug conjugate ladiratuzumab vedotin, a potential rival to Gilead Sciences’ Trodelvy. Merck and its partner are testing the ADC both as a monotherapy and in combination with Keytruda in TNBC.