Stepping on Roche's toes, Merck cuts into SCLC niche with third-line Keytruda OK
In the increasingly crowded checkpoint race, small cell lung cancer has been a rare area where Roche, a second runner-up, has a lead over the entrenched leaders Merck and Bristol-Myers Squibb. But Merck is finally making some headway in that direction with the latest approval for its PD-1 star.
The latest green light endorses Keytruda in the third-line treatment of metastatic SCLC, where it would be given to patients whose disease either don’t respond to or relapse after chemotherapy, which would have followed at least one prior line of therapy.
To illustrate the significance of this accelerated OK, Merck quoted Patrick Ott of Dana-Farber: “Small cell lung cancer, which accounts for 10 to 15% of all lung cancers, is often diagnosed at an advanced stage where the prognosis is very poor and there have historically been limited treatment options.”
That’s also why Roche’s success on this front was viewed as a landmark achievement. When Tecentriq plus chemo (carboplatin/etoposide) was approved for frontline use in March, it marked the first new option in more than two decades for treatment-naive patients whose small cell lung cancer has spread.
Perhaps underscoring a desperate need for improvements in this space, the regimen was heralded for hitting a median overall survival rate of 12.3 months, compared to 10.3 months for chemo alone — a significant 30% drop in the risk of death. The PFS was 5.2 months versus 4.3 months with a hazard ratio of a more modest 0.77.
Note, also, that Bristol-Myers’ Opdivo has failed to beat the standard of care in the second-line setting.
Meanwhile, Merck based its application on pooled data from two basket trials, KEYNOTE-158 and KEYNOTE-028, clinging to response rates as the key measures. Based on their analysis, Keytruda induced an ORR of 19% — 2% complete and 17% partial. Among the 16 responding patients, 94% had a response for six months or longer.
Benjamin Levy, a lung cancer specialist at Johns Hopkins with no stated ties to either group, told OncLive in the wake of Roche’s win that new Keytruda data will need to be “astounding” in order to replace the use of Tecentriq (atezolizumab), which blocks PD-L1.
“If the data turn out to be the same, it would be hard for physicians to change their practice of adding atezolizumab to chemotherapy,” Levy said. “Nevertheless, I look forward to the data and I look forward to seeing if a PD-1 inhibitor confers the same benefit that we have seen with atezolizumab.”
While this marks Keytruda’s first indication for SCLC, Merck has dramatically altered the NSCLC landscape since 2015, quadrupling the 5-year survival rate of patients who had not been previously treated with chemo from 5.5% to 23.2%.
You can expect the giant to seize on any new frontiers to grow its commanding lead.
Social image: Shutterstock