AT ESMO 2016

COPENHAGEN (FRONTLINE MEDICAL NEWS) – Adding the PD-1 checkpoint inhibitor pembrolizumab (Keytruda) to a standard platinum-doublet chemotherapy regimen nearly doubled response rates among patients with previously untreated advanced nonsquamous non–small cell lung cancer, but did not result in an overall survival advantage, results of a phase II trial show.

After a median follow-up of 10.6 months, the objective response rate among patients randomized to receive carboplatin and pemetrexed plus pembrolizumab was 55%, compared with 29% for patients treated with the platinum doublet alone, reported Corey J. Langer, MD , from the Abramson Cancer Center of the University of Pennsylvania, Philadelphia.

“Pembrolizumab in combination with carboplatin-pemetrexed is tolerable, has a readily manageable side effect profile, and this combination could eventually be an effective treatment option for patients with chemotherapy-naive advanced nonsquamous non–small cell [lung cancer],” he said at a briefing at the European Society for Medical Oncology Congress.

Dr. Langer presented results on one cohort in the KEYNOTE 021 trial , a phase II, randomized, open-label multicohort study looking at pembrolizumab in combination with chemotherapy or immunotherapy.

In this cohort, 123 patients with untreated stage IIIB or IV nonsquamous non–small cell lung cancer with no activating EGFR mutations or ALK translocations were randomly assigned to receive either pembrolizumab 200 mg every 3 weeks for 2 years plus carboplatin dosed to the area under the curve and infused at 5 mg/mL per min plus pemetrexed 500 mg/m2 every 3 weeks for four cycles, or to chemotherapy alone.

Following completion of the trial, patients randomized to chemotherapy could be switched over to pembrolizumab at the same dose and scheduled for up to 2 years.

As noted, for the primary endpoint of confirmed objective response rates, the rate in the pembrolizumab/chemo group was nearly double that of the chemo-alone group (55% vs. 29%, P = .0016).

Among 33 patients on the pembrolizumab/chemo combination and 18 on chemo alone who had clinical responses according to independent central review, the median time to response was 1.5 months vs. 2.7 months, respectively. The median duration of response had not been reached in either trial arm at the time of data cutoff, and 88% and 78% of patients, respectively, had ongoing treatment responses.

Progression-free survival, a secondary endpoint, was also significantly better with the combo, with a hazard ratio of 0.53 (P = .0102).

There was no difference in overall survival, however: 75% of patients on the combination were alive at 1 year, compared with 72% of the patients on chemo alone.

Grade 3 or greater treatment-related adverse events were seen in 39% of patients on pembrolizumab, compared with 26% of patients on chemotherapy.

The most common grade 3 or greater adverse events in the combination arm were anemia, decreased neutrophil count, acute kidney injury, decreased lymphocyte count, fatigue, neutropenia, sepsis, and thrombocytopenia. In the chemotherapy-alone group, the most common grade 3 or greater events were anemia, decreased neutrophil count, pancytopenia, and thrombocytopenia.

There were three deaths, one from sepsis each in the pembrolizumab-treated group and chemotherapy alone group, and one from pancytopenia in the chemo alone group.

One (2%) of 59 patients in the pembrolizumab plus chemotherapy group experienced treatment-related death because of sepsis, compared with two (3%) of 62 patients in the chemotherapy group.

Invited discussant Jean-Charles Soria, MD, chair of drug development at Gustave Roussy Cancer Center in Paris, said that although the findings of the trial are “intriguing,” there were not enough patients to allow for drawing significant conclusions about the potential use of the combination in clinical practice.

op@frontlinemedcom.com

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