Keytruda shows improved overall survival for metastatic head and neck squamous cell carcinoma in final analysis of phase III KEYNOTE-048 trial.

Merck announced the presentation of the final analysis of the pivotal Phase III KEYNOTE-048 trial investigating Keytruda, Merck’s anti-PD-1 therapy, as monotherapy and in combination with chemotherapy, for the first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #6000). Data include the first-time presentation of certain overall survival (OS) hypotheses from the Keytruda in combination with chemotherapy study arm based on PD-L1 expression and the Keytruda monotherapy study arm in the total patient population. Results of an interim analysis were presented at the European Society for Medical Oncology (ESMO) 2018 Congress and demonstrated superior OS outcomes for Keytruda in combination with chemotherapy in the total population and Keytruda monotherapy in patients whose tumors expressed PD-L1 with Combined Positive Score (CPS) ?20 and CPS ?1 compared with the EXTREME regimen, the current standard of care.

The new findings presented from the final analysis showed that Keytruda in combination with chemotherapy (carboplatin or cisplatin plus 5-FU) reduced the risk of death by 40% in patients whose tumors expressed PD-L1 with CPS?20, demonstrating significantly longer OS (14.7 months [95% CI, 10.3-19.3]) compared with the EXTREME regimen (cetuximab with carboplatin or cisplatin plus 5-fluorouracil [5-FU]), the current standard of care (11.0 months [95% CI, 9.2-13.0]) (HR=0.60 [95% CI, 0.45-0.82]; p=0.0004). For the dual primary endpoint of progression-free survival (PFS), statistical significance was not achieved for Keytruda in combination with chemotherapy in the CPS greater than 20 population compared with the EXTREME regimen (HR=0.73 [95% CI, 0.55-.97]; p=0.0162). New findings for the CPS greater than 1 population showed Keytruda in combination with chemotherapy reduced the risk of death by 35% in these patients, with significantly longer OS (13.6 months [95% CI, 10.7-15.5]) compared with the EXTREME regimen (10.4 months [95% CI, 9.1-11.7]) (HR=0.65 [95% CI, 0.53-0.80]; p<0.0001). Per the sequential testing strategy, superiority for PFS was not tested in this population (HR=0.82 [95% CI, 0.67-1.00]). Results for OS with Keytruda monotherapy in the total population were consistent with the previously presented interim analysis, where non-inferiority was demonstrated (HR=0.83 [95% CI, 0.70-0.99]; p=0.0199), with a median OS of 11.5 months (95% CI, 10.3-13.4) for Keytruda monotherapy in the total population compared with 10.7 months (95% CI, 9.3-11.7) for the EXTREME regimen. There was no difference in PFS between Keytruda monotherapy in the total population and the EXTREME regimen (HR=1.34 [95% CI, 1.13-1.59]).