- Merck & Co. on Monday reported adding its cancer drug Keytruda to chemotherapy staved off disease progression longer than chemo alone in patients with small cell lung cancer. But the immunotherapy didn’t appear to keep patients alive significantly longer.
- Roche’s competing drug Tecentriq received approval in March 2019 to treat a similar group of patients based on the results of a trial that demonstrated it significantly delayed progression and death. AstraZeneca’s drug Imfinzi also has demonstrated that it improves overall survival.
- Keytruda is the biggest seller in the PD-(L)1 class of drugs, with sales on track to hit $11 billion in 2019. Competitors are eager to steal some of that market share, and beating Keytruda in small cell lung cancer could help.
Small cell disease represents about 10% to 15% of all lung cancer cases. But with few options aside from chemotherapy, the tumor type represents an attractive area for immunotherapies like Keytruda (pembrolizumab), Tecentriq (atezolizumab), Imfinzi (durvalumab) and Bristol-Myers Squibb’s Opdivo (nivolumab).
Merck’s Keynote-604 trial was in “extensive stage” disease, which means the primary tumor has spread widely throughout the lung or to other parts of the body, as was the case with the Tecentriq IMPower-133 and Imfinzi CASPIAN trials.
Keytruda plus chemotherapy reduced the risk of disease progression or death by 25% but did not significantly reduce the risk of death when measured separately, a metric called overall survival. Tecentriq and Imfinzi showed a significant benefit on both progression-free and overall survival.
Comparing PD-(L)1s in small cell lung cancer
|Keytruda (KEYNOTE-604)||Imfinzi (CASPIAN)||Tecentriq IMPower-133|
|Overall survival||Not disclosed||13 months||12.3 months|
|Reduced risk of death vs. placebo||Not significant||27%||30%|
|Progression-free survival||Not disclosed||5.1 months||5.2 months|
|Reduced risk of progression vs. placebo||25%||22%||23%|
Sources: Company press releases, FDA labels
In its corporate presentation, AstraZeneca had said it planned to submit Imfinzi for approval in small cell lung cancer to the Food and Drug Administration before the end of 2019.
Missing the mark on overall survival does not preclude Merck from asking the FDA for a wider approval, however, as a benefit on progression free survival could be enough to satisfy regulators. Keytruda is currently cleared to treat small cell lung cancer that’s progressed after chemo and at least one other drug.
Cantor Fitzgerald analyst Louise Chen wrote in a Jan. 6 note to clients that presentation of KEYNOTE-604 data at a medical meeting ” will be important when cross-comparing the trials.”
Roche has described small cell lung cancer as a market worth about $1 billion.
Bristol-Myers Squibb’s Opdivo has also been approved in small cell lung cancer, but as a third-line treatment. Subsequent studies have failed to meet their goal.
Jazz Pharmaceuticals, meanwhile, paid $200 million up front to the Spanish company PharmaMar to secure U.S. rights to lurbinectedin, an agent derived from a chemical found in sea squirts that is now under review by the FDA. That drug is intended to be used in relapsed small cell disease.
Small cell disease has been a challenge for drug developers. AbbVie canceled all work on an experimental drug called rovalpituzumab tesirine and took a $5.1 billion in impairment charges related to the acquisition of its originator, Stemcentrx.