Anti–PD-1 Antibodies for NSCLC and Renal Carcinoma

August 2014 Vol 7, Special Issue ASCO 2014 Payers' Perspectives in Oncology - Emerging Therapies
Caroline Helwick

Several presentations at ASCO 2014 focused on the use of the anti–programmed death (PD)-1 monoclonal antibodies in non–small-cell lung cancer (NSCLC) and in renal-cell carcinoma.

Nivolumab plus Ipilimumab
The phase 1 multicohort CA209-012 trial evaluated nivolumab as a single agent and in combination with ipilimumab, chemotherapy, and erlotinib. Nivolumab monotherapy in the first-line setting produced responses in 30% of patients, but the median duration of response was not reached. “Responses are ongoing in 4 of 6.

The progression-free survival (PFS) at 24 weeks was 60%, and the median PFS was 47.2 weeks in patients with nonsquamous histology and 15.1 weeks in patients with squamous tumors; the 1-year overall survival (OS) rate was 75%. The median OS was not reached at the time of analysis.

All of the responders expressed the PD-L1 ligand, which may possibly serve as a biomarker of activity. In this subgroup, the results were most impressive, with a 1-year OS rate of 80%.

Could 2 immune checkpoint inhibitors be better than 1? That question was asked in a cohort of the CA209-012 trial involving 49 chemotherapy-naïve patients receiving nivolumab plus ipilimumab and followed by nivolu­mab monotherapy until progression. Responses were ongoing in 75% of responders at the time of the analysis.

At 24 weeks, the median PFS ranged from 20% to 51%, and the median PFS was 14.4 weeks to 16.1 weeks. The median OS was 44 weeks in 1 subset and was not reached in the other arms.

“The findings suggest this combination may be suitable for PD-L1–positive and –negative patients,” said Scott J. Antonia, MD, of H. Lee Moffitt Cancer Center, Tampa, FL.

Pembrolizumab (MK-3475) in Previously Treated Patients
A phase 1 study of 217 patients with previously treated NSCLC showed strong antitumor activity for pembrolizumab, especially among patients expressing PD-L1. The objective response rate was 20% and was higher among patients expressing PD-L1 (23%) than in those who did not (9%). Of the former patients who responded, 82% continue to receive treatment.

Nivolumab in Renal-Cell Carcinoma
Results from the phase 2 CheckMate-010 trial in advanced kidney cancer showed that single-agent nivolu­mab produced responses in 20% to 22% of patients and yielded 1-year survival rates of 63% to 72%. In previously treated patients, the median OS was 25 months with 2-mg/kg dosing.

In a phase 1b trial of previously treated as well as treatment-naïve patients, nivolumab combined with ipilimumab produced responses in 43% to 48% of patients and was associated with a 24-week PFS rate of 65%.

“These data are encouraging as we seek to identify new treatments for patients, particularly those who pro­gress following treatment with antiangiogenic therapy,” said Robert Motzer, MD, of Memorial Sloan Kettering Cancer Center, New York City.

Tolerability of Anti–PD-1 Agents
The toxicities associated with anti–PD-1 agents are primarily immune-­related and transient, although some can be concerning. As a single agent, nivolumab was associated with adverse events in 85% of patients, but only 20% were grade 3/4. For the combination of nivolumab and ipilimumab, grade 3/4 adverse events were reported by 49% of patients across the arms, primarily during induction and not maintenance. Serious diarrhea and colitis occurred in 8% of patients, and liver enzymes were elevated in 6% of patients. Approximately 33% of patients discontinued treatment as a result of adverse events, and 3 patients died as a result of drug-related toxicities (1 each from colitis, pulmonary hemorrhage, and toxic epidermal necrolysis).

When given with chemotherapy, treatment-related grade 3/4 adverse events occurred in 45% of patients receiving anti–PD-1.

With pembrolizumab, almost 66% of patients had at least 1 drug-related adverse event of any grade, and 10% of patients had grade 3/4 toxicity. Grade 3/4 pneumonitis was observed in 4 patients.

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Last modified: August 21, 2014
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