Merck's Keytruda steps up to face Roche's Tecentriq with FDA OK in triple-negative breast cancer

The FDA based Keytruda’s nod on data from the phase 3 Keynote-355 trial, a study Merck first declared a success in February. (Merck)

Roche’s Tecentriq has some company in triple-negative breast cancer—and it’s from the best-selling immuno-oncology drug.

Merck’s Keytruda, used in tandem with chemo, has won FDA accelerated approval in triple-negative breast cancer. The nod is limited to patients whose tumors express high levels of biomarker PD-L1 at a combined positive score of at least 10.

Friday’s green light tees up a new front of competition between Keytruda and first-mover Tecentriq. So far, cases can be made in both drugs’ favor.

The FDA based Keytruda’s nod on data from the phase 3 Keynote-355 trial, a study Merck first declared a success in February. It showed that Keytruda and chemo slashed the risk of disease progression or death by 35% against solo chemo in patients with PD-L1 levels of 10 or higher, according to data unveiled ahead of this year’s American Society of Clinical Oncology (ASCO) virtual annual meeting.

The study is continuing to find out whether the Keytruda regimen can extend patients’ lives, and the new go-ahead is contingent on Merck showing additional positive benefits.

RELATED: ASCO: Merck steps up to challenge Roche with big Keytruda breast cancer win

In comparison, Tecentriq became the first I-O drug approved in the hard-to-treat cancer type last March. That accelerated nod, for Tecentriq use alongside Celgene chemotherapy Abraxane (paclitaxel protein-bound), is meant for PD-L1-positive patients. It was based on data from the phase 3 IMpassion130 trial, which showed the pair could cut the risk of disease worsening or death by 40% over Abraxane monotherapy in that PD-L1-positive population.

Final analysis found the cocktail could cut the risk of death by 33%, as presented at this year’s European Society for Medical Oncology (ESMO) virtual annual meeting.

Tecentriq defines PD-L1-positive as having PD-L1-stained tumor-infiltrating immune cells [IC] covering at least 1% of the tumor area. In a statement, Merck said its CPS 10 score is roughly equivalent to Roche's IC 1%, as their prevalence in TNBC are both around 40%.

Tecentriq’s approval came 20 months before Keytruda’s, and let’s not forget Roche’s strong foothold in breast cancer in general, with its big HER2 franchise, including Herceptin, Perjeta and Kadcyla.

But as Evercore ISI analyst Umer Raffat has previously noted, the Merck regimen allows physicians a wider range of chemo options than Roche’s did. The Keynote-355 trial used thee chemotherapies—Abraxane, paclitaxel, or a combo of gemcitabine and carboplatin—while IMpassion130 only studied Abraxane.

RELATED: ESMO: Roche's mixed results put Tecentriq's triple-negative breast cancer use into question

That detail may not have made much of a difference for physicians on the ground in the past, but concerning data from late last year will likely deter physicians from trying Tecentriq with other chemo types.

In a public notice issued in September, the agency alerted physicians not to use the Tecentriq-paclitaxel combo in previously untreated TNBC. Detailed data unveiled at this year’s ESMO meeting from the IMpassion131 trial showed that the combo not only didn’t slow tumor progression any better than solo chemo did, but also even increased the likelihood of death.

Both Merck and Roche, meanwhile, are eyeing earlier TNBC use. Adding Keytruda to chemo ahead of surgery cleared all signs of cancer cells in surgically removed tissue for 64.8% of newly diagnosed TNBC patients, compared with 44.1% for solo chemo, according to data from the phase 3 Keynote-522 study.

In the IMpassion031 trial, 57.6% of patients who got a combination of Tecentriq and chemo ahead of surgery hit that mark, versus 41.1% for chemo alone, an improvement that Roche said was both statistically significant and clinically meaningful.

Looking beyond its Keytruda-chemo pairing, Merck recently licensed an investigational antibody-drug conjugate from Seattle Genetics. Called ladiratuzumab vedotin, the drug targets LIV-1, which is upregulated in TNBC. Trials are ongoing for the drug both as a monotherapy and in combination with Keytruda.

Editor's Note: The story has been updated to clarify Tecentriq's and Keytruda's PD-L1 populations.