Keytruda + Alimta + chemotherapy extends OS and reduces death risk in KEYNOTE 189 study for first line NSCLC patients.- Merck Inc.

Merck Inc., announced results from KEYNOTE-189, a pivotal Phase III trial evaluating Keytruda , Merck�s anti-PD-1 therapy, in combination with pemetrexed (Alimta) and cisplatin or carboplatin for the first-line treatment of metastatic nonsquamous non-small cell lung cancer (NSCLC). Findings showed that the Keytruda-pemetrexed-platinum chemotherapy combination significantly improved overall survival (OS), reducing the risk of death by half compared with chemotherapy alone (HR=0.49 [95% CI, 0.38-0.64]; p<0.00001). in pre-specified exploratory analyses an os benefit was observed regardless of pd-l1 expression in the three pd-l1 categories that were evaluated including: patients whose tumors were negative for pd-l1 hr="0.59" 95 ci 0.38-0.92 patients whose tumors had pd-l1 tumor proportion scores tps of 1-49 percent hr="0.55" 95 ci 0.34-0.90 and patients who had a tps of greater than or equal to 50 percent hr="0.42" 95 ci 0.26-0.68. the addition of keytruda to pemetrexed plus platinum chemotherapy also achieved a significant improvement in progression-free survival pfs with a reduction in the risk of progression or death of nearly half for patients in the keytruda combination arm compared with chemotherapy alone hr="0.52" 95 ci 0.43-0.64 p><0.00001). a pfs improvement in the keytruda combination group was observed in patients whose tumors were negative for pd-l1 hr="0.75" 95 ci 0.53-1.05 patients with a tps of 1-49 percent hr="0.55" 95 ci 0.37-0.81 and patients with a tps greater than or equal to 50 percent hr="0.36" 95 ci 0.25-0.52. these results were presented in a plenary session at the american association for cancer research aacr annual meeting 2018 abstract ct075 with simultaneous publication in the new england journal of medicine.>

Additional Data and Safety Information from KEYNOTE-189 (Abstract #CT075) :KEYNOTE-189, a randomized, double-blind, placebo-controlled, Phase III study, evaluated Keytruda in combination with pemetrexed and cisplatin or carboplatin, compared with pemetrexed and cisplatin or carboplatin alone, in 616 untreated patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression. Patients had no sensitizing EGFR or ALK genomic tumor aberrations, and had not previously received systemic therapy for advanced disease. The dual primary endpoints were OS and PFS; secondary endpoints include overall response rate (ORR) and duration of response (DOR). With a median follow-up of 10.5 months (range, 0.2-20.4), Keytruda in combination with pemetrexed and a platinum chemotherapy demonstrated superior improvements in OS, with a 51 percent reduction in the risk of death, compared with pemetrexed plus platinum chemotherapy alone (HR=0.49 [95% CI, 0.38-0.64]; p<0.00001). this finding includes the 50 percent of patients randomized to the chemotherapy alone group who discontinued all study therapy n="170)" and went on to receive subsequent anti-pd-1 or pd-l1 therapy including 67 patients who received keytruda monotherapy as part of study crossover. median os was not reached in the keytruda combination group 95 ci not estimable and was 11.3 months in the chemotherapy alone group 95 ci 8.7-15.1. in the study 69.2 percent of patients were estimated to be alive at 12 months in the keytruda treatment group 95 ci 64.1-73.8 compared with 49.4 percent in the chemotherapy alone group 95 ci 42.1-56.2. in keynote-189 there was also a significant improvement in pfs for keytruda in combination with pemetrexed and platinum chemotherapy with a 48 percent reduction in the risk of progression or death compared with pemetrexed plus platinum chemotherapy alone hr="0.52" 95 ci 0.43-0.64 p><0.00001). the median pfs was 8.8 months for the keytruda combination 95 ci 7.6-9.2 compared with 4.9 months for chemotherapy alone 95 ci 4.7-5.5. the percentage of patients who were alive with no progression of disease at 12 months was 34.1 percent in the keytruda combination group 95 ci 28.8-39.5 which was nearly double the percentage of the pemetrexed plus platinum chemotherapy group 17.3 percent 95 ci 12.0-23.5. in addition improvements in os and pfs were observed in other patient subgroups evaluated including age sex egog performance-status score smoking status brain metastases at baseline and type of platinum chemotherapy prescribed carboplatin or cisplatin. in the study keytruda plus pemetrexed and a platinum chemotherapy also showed an orr that was more than double the orr of chemotherapy alone 47.6 percent 95 ci 42.6-52.5 compared to 18.9 percent 95 ci 13.8-25.0 respectively p><0.00001). among patients in the keytruda arm the median duration of response was 11.2 months range 1.1 to 18.0 months compared with 7.8 months in the chemotherapy alone group range 2.1 to 16.4 months. the improvement in response rate occurred in all pd-l1 patient subgroups. the safety of keytruda was consistent with what has been seen in previous trials among patients with metastatic nsclc. grade 3-5 adverse events from any cause occurred in 67.2 percent of patients in the keytruda plus pemetrexed and platinum chemotherapy group and 65.8 percent in the chemotherapy alone arm.>

Comment:In KEYNOTE-189 study, treatment with Keytruda plus chemotherapy cut the risk of death by 51% compared to chemo alone in patients with metastatic non-squamous non-small cell lung cancer (NSCLC). Across patients who expressed higher levels of PD-L1, a biomarker correlated with responsiveness to immunotherapy, an even greater risk reduction of 58% was reported. After one year, nearly 70% of patients on treatment were alive compared to about 50% of those receiving chemo. Those overall survival results are likely to be practice changing, according to Alice Shaw, an oncologist at the Massachusetts General Hospital Cancer center and co-chair of the clinical trials committee for AACR's annual meeting.