By Shreeya Nanda
Phase I results published in the Journal of Clinical Oncology suggest that nivolumab, either given alone or alongside platinum-based doublet chemotherapy, could have a role in the first-line treatment of advanced non-small-cell lung cancer (NSCLC).
In the first of two papers, Scott Gettinger (Yale Cancer Center in New Haven, Connecticut, USA) and co-investigators, who report on the monotherapy part of the CheckMate 012 trial, say that the anti-programmed death 1 antibody demonstrated "robust activity" in the first-line setting and "a tolerable safety profile".
Among 52 patients with stage IIIB or IV disease not previously treated with chemotherapy, intravenous nivolumab 3 mg/kg every 2 weeks induced a complete response in four and a partial response in eight patients during a median 14.3 months of follow-up, equating to an objective response rate of 23%.
The researchers say that the responses were durable, with median duration of response not reached at the time of analysis, and the majority (75%) occurred by the first tumour assessment at week 11.
Progression-free survival (PFS) was a median of 3.6 months, and 41% of patients remained progression-free at 24 weeks.
Nineteen percent of patients experienced treatment-related side effects of grade 3 or 4, with rash the only event occurring in more than one patient (n=2), and 12% discontinued treatment as a result of related toxicity.
Although "limited by a highly selected population without randomization to standard chemotherapy", the efficacy results are "encouraging, far exceeding expectations with chemotherapy alone", conclude Gettinger et al.
In the second paper, also based on CheckMate 012 data, Naiyer Rizvi, from Columbia University Medical Center in New York, USA, and team evaluated the addition of nivolumab to the current standard chemotherapy regimens used in first-line NSCLC.
The 56 participants, who had stage IIIB or IV NSCLC and had not received prior chemotherapy for advanced disease, were assigned by histology to receive nivolumab 10 mg/kg either alongside gemcitabine-cisplatin (squamous histology), pemetrexed-cisplatin (nonsquamous histology) or paclitaxel-carboplatin (all histologies), or nivolumab 5 mg/kg plus paclitaxel-cisplatin (all histologies), for four 21-day cycles. All patients received nivolumab monotherapy after completion of dual treatment.
Of the 12 patients given nivolumab plus gemcitabine-cisplatin, 33% achieved a response, as did 43% of the 14 patients given the lower dose of nivolumab plus paclitaxel-carboplatin and 47% of the 15 participants each given nivolumab 10 mg/kg together with pemetrexed-cisplatin or paclitaxel-carboplatin.
As seen for patients given nivolumab monotherapy, the majority (71%) of responses were achieved by week 10. And 42% of the responses were ongoing after a median follow-up of 19.0 months, report Rizvi et al.
Median PFS times ranged from 4.8 months to 7.1 months and 24-week PFS rates from 38% to 71% across the treatment arms.
Altogether grade 3 or 4 treatment-related adverse events were observed in almost half (45%) of the participants, with pneumonitis (7%), fatigue (5%) and acute renal failure (5%) the most common events. Rizvi and team say that the most common toxicities were as expected with doublet chemotherapy alone, but the rate of toxicity-related discontinuation (21%) was higher with the combination.
"Collectively, our results suggest that nivolumab plus [platinum-based doublet chemotherapy] may provide benefit beyond single-modality chemotherapy and may represent a treatment option for patients with rapidly progressing disease", they conclude.
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J Clin Oncol 2016; Advance online publication