Skip to main content

Anti–PD-1 Antibodies for NSCLC and Renal Carcinoma

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

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.

Related Items
Novel Target: RARA Agonist plus Azacitidine Active in Relapsed or Refractory Acute Myeloid Leukemia
Phoebe Starr
February 2021 Vol 14, Special Issue: Payers' Perspectives in Oncology published on February 24, 2021 in Emerging Therapies
Magrolimab, First CD47 Antibody, Shows Promise in Combination with Azacitidine in Unfit Patients with Acute Myeloid Leukemia
Wayne Kuznar
February 2021 Vol 14, Special Issue: Payers' Perspectives in Oncology published on February 24, 2021 in Emerging Therapies
Oral Vodobatinib Elicits Durable Responses in Heavily Pretreated Patients with Chronic Myeloid Leukemia
Chase Doyle
February 2021 Vol 14, Special Issue: Payers' Perspectives in Oncology published on February 24, 2021 in Emerging Therapies
First-Line Mosunetuzumab Safe and Effective in Older Patients with Diffuse Large B-Cell Lymphoma
Chase Doyle
February 2021 Vol 14, Special Issue: Payers' Perspectives in Oncology published on February 24, 2021 in Emerging Therapies
Tumor-Infiltrating Lymphocyte Therapy Induces Responses Across Wide Range of Patients with Advanced Melanoma
Wayne Kuznar
August 2020 Vol 13, Special Issue: Payers' Perspectives in Oncology published on August 17, 2020 in Emerging Therapies
Last modified: August 30, 2021