European Commission approves Keytruda and Inlyta combination for first line treatment of renal cell carcinoma. Merck Inc.,

Merck Inc., has announced that the European Commission has approved Keytruda, Merck�s anti-PD-1 therapy, in combination with Inlyta (axitinib), a tyrosine kinase inhibitor, for the first-line treatment of patients with advanced renal cell carcinoma (RCC). This approval includes patients in all IMDC risk groups.

It is based on findings from the pivotal Phase III KEYNOTE-426 trial, which demonstrated that Keytruda in combination with axitinib reduced the risk of death by 47% compared with sunitinib (HR=0.53 [95% CI, 0.38, 0.74]; p=0.00005) in patients with advanced RCC. The KEYTRUDA with axitinib combination also demonstrated an improvement in progression-free survival.

In KEYNOTE-426, Keytruda in combination with axitinib demonstrated a statistically significant improvement in OS, reducing the risk of death by 47% compared with sunitinib (HR=0.53 [95% CI, 0.38, 0.74]; p=0.00005). There were 59 events (14%) observed in patients receiving Keytruda with axitinib (n=432) versus 97 events (23%) in patients receiving sunitinib (n=429). Median OS was not reached with either treatment regimen. The Keytruda with axitinib combination also demonstrated improved PFS, with a reduction in the risk of progression or death of 31% compared with sunitinib (HR=0.69 [95% CI, 0.57, 0.84]; p=0.00012). There were 183 events (42%) observed in patients receiving Keytruda with axitinib versus 213 events (50%) in patients receiving sunitinib. Median PFS was 15.1 months (95% CI, 12.6, 17.7) in patients who received the Keytruda with axitinib combination versus 11.0 months (95% CI, 8.7, 12.5) for those who received sunitinib. In the study, the ORR was 59% for patients who received the Keytruda with axitinib combination (95% CI, 54, 64) and 36% for those who received sunitinib (95% CI, 31, 40) (p<0.0001), with a complete response rate of 6% and 2% and a partial response rate of 53% and 34%, for patients who received the keytruda with axitinib combination versus sunitinib, respectively. the median dor was not reached (range, 1.4+ to 18.2+ months) with the keytruda with axitinib combination and was 15.2 months (range 1.1+ to 15.4+ months) with sunitinib.>

In KEYNOTE-426, the safety of Keytruda in combination with axitinib was investigated in patients with previously untreated, advanced RCC. When Keytruda in combination with axitinib is given, higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to Keytruda alone have been reported in patients with advanced RCC. With the combination of Keytruda and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) have been reported. Among patients with advanced RCC, the most frequent adverse reactions were diarrhea (54%), hypertension (45%), fatigue (38%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysaesthesia syndrome (28%), nausea (28%), ALT increased (27%), AST increased (26%), dysphonia (25%), cough (21%) and constipation (21%). Incidences of Grades 3-5 adverse reactions were 76% for the Keytruda with axitinib combination and 71% for sunitinib.