Treatment with the immune checkpoint antibody, nivolumab (Opdivo), resulted in a 14.5% overall response rate, including one complete response in a phase II trial of heavily pretreated squamous non-small cell lung patients (NSCLC).
Treatment with the immune checkpoint antibody, nivolumab (Opdivo), resulted in a 14.5% overall response rate, including one complete response in a phase II trial of heavily pretreated squamous non-small cell lung patients (NSCLC). The median duration of response has not yet been reached, and currently, 13 of the 17 responses (77%) are ongoing as of the last trial assessment.
The results from the CheckMate 063 clinical trial with the antiprogrammed cell death-1 (anti-PD-1) immunotherapy antibody are published in The Lancet Oncology. The initial results were previously presented at the 2014 Multidisciplinary Symposium in Thoracic Oncology.
An additional 30 patients on the trial (26%) had stable disease with a median duration of 6.0 months. The median time to response was 3.3 months.
Of the 17 responders, eight (47%) had progressive disease in response to their previous treatment.
“Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomized, controlled, phase III studies of first-line and second-line treatment,” concluded the study authors.
The single-arm trial enrolled 117 patients in the United States and Europe who had failed two or more therapies for their advanced disease. Sixty-five percent of the patients had failed at least three prior therapies. The median patient age on trial was 65. Thirty-three percent of patients had received a prior anti-EGFR tyrosine kinase inhibitor and all patients had received a platinum-based chemotherapy.
Patients received 3 mg/kg of nivolumab as an intravenous infusion every 2 weeks until disease progression or unacceptable adverse events. Patients received a median of 6 nivolumab doses.
Patients with refractory squamous NSCLC have no therapeutic options after failing two systemic treatments and a short overall survival of less than 6 months. The two-year survival rate is only 3%.
The median progression-free survival (PFS) was 1.9 months, and the PFS rate at 6 months and 1 year was 25.9% and 20.0%, respectively. Median overall survival was 8.2 months with an overall survival rate at 1 year of 40.8%.
Both patients with tumors expressing PD-L1, the ligand for PD-L, and those whose tumors lacked PD-L1 expression responded to treatment. Of the 25 PD-L1 positive patients, six (24%) had a partial response while seven of the 51 (14%) of the PD-L1-negative patients had a partial response.
Treatment related grade 3-4 adverse events included fatigue (4%), pneumonitis (3%), and diarrhea (3%). There were two treatment-associated deaths; one from pneumonitis and another from an ischemic stroke in two patients who had multiple comorbities and progressive disease. Discontinuation due to an adverse event occurred in 12% of patients.
In a commentary accompanying this study publication, Ramon Andrade de Mello, MD, and InÃ©s Pousa, PhD, of the University ofAlgarve, Faro, Portugal, and Deolinda Pereira, MD of the Portuguese Oncology Institute, Porto, Portugal, highlight two concerns with the study: the use of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 to evaluate responses rather than the newer immune-related response criteria better suited for the types of responses seen to immunotherapies, and the role of nivolumab in targeting brain metastases, which was not well-addressed in the study.
Nivolumab is currently approved by the US Food and Drug Administration (FDA) for treatment of metastatic melanoma. In January of 2015, a phase III trial comparing nivolumab to docetaxel in previously treated metastatic squamous NSCLC was stopped early because the study demonstrated a superior overall survival of patients in the nivolumab therapy arm.
Bristol-Myers Squibb, the manufacturer of nivolumab, has submitted a marketing authorization application to the European Medicines Agency for use of nivolumab in NSCLC. The company also has a rolling submission with the FDA of nivolumab as a third-line therapy for squamous NSCLC.