When Roche’s Tecentriq flopped as part of a chemo combo regimen in triple-negative breast cancer (TNBC), questions were naturally extended as to whether Merck's in-class rival Keytruda would falter when paired with the same chemo drug, paclitaxel.
But now, Merck has data showing that wasn't the case—and that, on the contrary, Keytruda helps fight TNBC no matter which approved chemo regimen it's paired with.
Adding Keytruda to chemo drug paclitaxel cut the risk of disease progression or death by 67% in previously untreated metastatic TNBC patients whose tumors expressed the biomarker PD-L1 at a combined positive score (CPS) of at least 10. The phase 3 trial data were presented at the San Antonio Breast Cancer Symposium (SABCS).
When paired with Bristol Myers Squibb’s Abraxane, or paclitaxel protein-bound (nab-paclitaxel), Keytruda slashed that risk by 43% versus solo chemo and by 23% when used in tandem with gemcitabine and carboplatin. Keytruda won an FDA accelerated approval in November for use alongside any of those three chemo options thanks to data from the Keynote-355 trial.
Roy Baynes, Merck’s chief medical officer and head of global clinical development, called the paclitaxel subgroup’s 67% showing “remarkable,” while pointing out that all three groups’ progression-free survival improvements were either statistically significant or clinically meaningful.
“This speaks to the value of the [Keytruda] combination in triple-negative breast cancer in PD-L1-enriched populations and it seems to be irrespective of chemotherapy, which is totally different from what others have found,” Baynes said.
His comments make a subtle reference to Tecentriq. The Roche PD-L1 became the first checkpoint inhibitor to move into TNBC based on data from the phase 3 IMpassion130 study, showing Tecentriq plus Abraxane significantly cut the risk of disease worsening or death by 40% over Abraxane alone in mTNBC patients with PD-L1-stained tumor-infiltrating immune cells covering at least 1% of the tumor area.
But Roche suffered a surprising setback when it tried to repeat the win in the IMpassion131 trial. In that trial, the pairing of Tecentriq and paclitaxel did even worse than solo chemo at extending patients’ lives, according to data presented at this year’s European Society of Medical Oncology virtual meeting. Noting that failure, the FDA issued an advisory, warning physicians not to replace nab-paclitaxel with paclitaxel when using Tecentriq in TNBC.
But unlike Tecentriq, which had two trials for each chemo pairing, the number of patients in each Keynote-355 subgroup was too small to power a separate statistical analysis. Baynes, though, argued that the new subgroup showing “speaks to the convergent validity across the various forms of chemotherapy.”
The result? Merck can confidently tout Keytruda’s TNBC utility across the three chemo regimens, while Tecentriq is constrained to Abraxane.
Having different options is important for physicians, Baynes said. Paclitaxel is one of the most common chemotherapies. Nab-paclitaxel, meanwhile, is used more in the U.S., but not really in Europe. Platinum-based chemo is the choice of certain oncologists, and it has been shown as the most active chemotherapy in TNBC.
Keytruda’s TNBC approval currently only applies to the population whose tumors bear a CPS of 10 or more. At SABCS, Merck also unveiled data from patients with PD-L1 scores at or over 1. In that group, Keytruda-plus-chemo only cut the risk of disease progression or death by 26%, a result that wasn't statistically significant; plus, whatever improvement it demonstrated was clearly driven by the CPS 10-plus group.
Still, the trial remains ongoing to find out whether the Keytruda regimen can extend patients’ lives.
Besides mTNBC, Merck’s waiting for an FDA decision for the use of Keytruda, in combination with platinum-based chemo, in high-risk early-stage TNBC before and right after surgery. An FDA action date has been set for March 29.