Merck & Co has reported mixed results from a phase 3 trial of its cancer immunotherapy Keytruda, as it tries to extend the use of the drug into first-line therapy for extensive-stage small cell lung cancer (SCLC).
The results of the KEYNOTE-604 trial show that when Keytruda (pembrolizumab) is added to chemotherapy it extends the time patients live without their cancer getting worse – progression-free survival or PFS – confirming the results of an earlier interim analysis.
The checkpoint inhibitor wasn’t able to improve overall survival (OS) however, which is considered a more robust indicator of the benefit of a cancer drug.
The trial enrolled 453 patients with newly diagnosed extensive-stage SCLC, who were randomly assigned to either Keytruda or placebo on top of standard first-line chemotherapy with etoposide and the clinical investigator’s choice of platinum-based chemotherapy.
At the moment, the only drug in the checkpoint inhibitor class of immuno-oncology agents to be approved for this patient group is Roche’s Tecentriq (atezolizumab), which was able to show a significant improvement in OS in the IMpower133 trial.
Further follow-up from that study has however suggested that the survival curves for placebo and Tecentriq had started to come together on further follow-up – at least according to an appraisal of the data by UK cost-effectiveness agency NICE which recently rejected use of Roche’s drug in this setting in draft guidance.
Another checkpoint inhibitor in development for this use is AstraZeneca’s Imfinzi (durvalumab), which is heading for regulatory decision in Europe and the US in previously-untreated SCLC later this year on the strength of data from the CASPIAN trial, which also showed a significant improvement in both PFS and OS.
The KEYNOTE-604 results suggest Merck may struggle to mirror the dominance it currently enjoys with Keytruda in the large non-small cell lung cancer (NSCLC) market to the SCLC category.
SCLC accounts for around 10% to 15% of all cases of lung cancer, according to Merck, and has a poor prognosis with a five-year survival rate of approximately 6%, across all stages of the disease at diagnosis.