Nivolumab has demonstrated encouraging activity and acceptable tolerability as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC), according to the results of two phase I, multicohort studies published in the Journal of Clinical Oncology.
In the first study, 52 patients were enrolled in the trial and assigned to receive nivolumab intravenously every 2 weeks until disease progression or unacceptable toxicity. The primary object of the trial was to observe the safety of the drug as a first-line treatment, but investigators also looked at objective response rate (ORR) and 24-week progression-free survival (PFS) rate. Overall survival (OS) was also included as an exploratory end point.
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Nearly three-fourths of all patients (71%) in the trial experienced a treatment-related adverse event of any grade, most commonly fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related adverse events, with grade 3 rash being the only serious, grade 3 to 4 treatment-related adverse event occurring in more than 1 patient. A total of 6 patients (12%) had to discontinue treatment due to the severity of their adverse events.
The confirmed ORR was 23% (12 of 52 patients), with 4 patients experiencing ongoing complete response. ORR was also found to be significantly better among patients who expressed programmed death-ligand 1 compared with those who did not (28% vs 14%, respectively). Median PFS was 3.6 months, 24-week PFS rate was 41%, and OS was 19.4 months with 1-year and 18-month rates of 73% and 57%, respectively.
Researchers concluded that nivolumab monotherapy demonstrated a durable response with a tolerable safety profile in patients with first-line advanced NSCLC.
The second study assigned 56 patients to receive nivolumab in addition to platinum-based chemotherapy with gemcitabine-cisplatin, pemetrexed-cisplatin,
or paclitaxel-carboplatin every three weeks for four cycles followed by nivolumab monotherapy. Investigators again focused their attention on determining the safety and tolerability of the regimens while also assessing the ORR and 24-week progression-free survival rate. OS and tumor programmed death ligand-1 expression were exploratory objectives.
Overall, there were no dose-limiting toxicities during the first 6 weeks of treatment, but 45% of patients (25 of 56 patients) did end up reporting grade 3 to 4 treatment-related adverse events. Additionally, 21% of patients (12 patients) discontinued all study therapy due to treatment-related adverse events.
Regimens of nivolumab 10 mg/kg plus pemetrexed-cisplatin and nivolumab 10 mg/kg plus paclitaxel-carboplatin had the highest ORR at 47% followed by nivolumab 5 mg/kg plus paclitaxel-carboplatin (43%) and nivolumab 10 mg/kg plus gemcitabine-cisplatin (33%). 24-week PFS rates were 51%, 71%, 38%, and 51% for nivolumab 10 mg/kg plus gemcitabine-cisplatin, nivolumab 10 mg/kg plus pemetrexed-cisplatin, nivolumab 10 mg/kg plus paclitaxel-carboplatin, and nivolumab 5 mg/kg plus paclitaxel-carboplatin, respectively.
The activity observed by each regimen was promising, researchers concluded, though they added that treatment discontinuation related to adverse events occurred much more frequently in patients treated with combination therapies.
