Adding Keytruda (pembrolizumab) to chemotherapy provides superior and more sustained tumor size reduction in patients with a type of metastatic non-small cell lung cancer (NSCLC), Merck’s Phase 3 trial shows.
The research, “Phase 3 study of carboplatin-paclitaxel/nab-paclitaxel (Chemotherapytherapy) with or without Keytrudalizumab (Keytruda) for patients (Patients) with metastatic squamous (Sq) non-small cell lung cancer (NSCLC),” was presented recently at the 2018 American Society of Clinical Oncology ASCO Annual Meeting in Chicago.
A treatment combination of Keytruda and chemotherapy – Alimta (pemetrexed) and carboplatin – has shown promise in patients with non-squamous NSCLC who had not received any therapy in a prior Phase 2 trial (NCT02039674). Patients had better response rates, lived longer without disease progression, and had longer lives compared to those who received just chemotherapy.
But Keytruda also shows activity in squamous NSCLC, leading scientists to consider that combining it with chemotherapy would be a rational strategy.
The KEYNOTE-407 Phase 3 trial (NCT02775435), which is recruiting patients, was designed to test this combination as a first-line treatment for squamous NSCLC patients, who were either fully active or only restricted in physically demanding activity.
Patients were divided by type of chemo medication, positive or negative expression of PD-L1 – a biomarker that predicts responses to Keytruda – and location (east Asia vs. other).
Then they were assigned randomly to either Paraplatin (carboplatin) and Taxol (paclitaxel) every three weeks, or weekly Abraxane (nab-paclitaxel) plus Keytruda or placebo, over four cycles. This was followed by Keytruda/placebo for a total of 35 treatments.
At the first preliminary analysis, 204 patients already had received treatment and had been followed for a median of 7.7 months. The majority were men; 48 percent were younger than 65, and 28 percent were fully active.
Also, 35 percent of patients tested negative for tumor PD-L1 expression, while 32 percent used Abraxane.
More patients receiving the combination experienced a reduction in tumor size than those on chemotherapy alone – 58.4 percent versus 35.0 percent. Also, 65.8 percent of patients in the combination group had a response that lasted six or more months, compared to 45.6 percent in control participants.
Incidence of severe (grade 3) or worse adverse events was 64.4 percent for Keytruda and 74.5 percent for chemo. No new safety concerns were observed.
“Adding [Keytruda] almost doubled the [overall response rate] of chemo for [patients] with untreated metastatic [squamous] NSCLC,” the researchers wrote.
They also commented that the treatment combination presents a tolerable safety profile.
Besides results of KEYNOTE-407, Merck, known as MSD outside the U.S. and Canada, also will present data about Keytruda in studies of melanoma, renal cell, cervical, merkel cell, and other cancers at ASCO 2018.
“With more data and longer follow-up across tumors and treatment settings, evidence continues to support the role of Keytruda as a foundational treatment for many types of cancer,” Roger M. Perlmutter, president, Merck Research Laboratories, said in a press release.
