Immunotherapy in Heavily Pretreated Advanced NSCLC
As reported in The Lancet Oncology by Garassino et al, the phase II ATLANTIC trial has shown durvalumab (Imfinzi) to be active in third- or later-line treatment of advanced non–small cell lung cancer (NSCLC).
Study Details
In the study, 444 patients from 139 sites in Asia, Europe, and North America with advanced NSCLC and disease progression following at least 2 previous systemic regimens, including platinum-based chemotherapy, and tyrosine kinase inhibitor therapy if indicated, were enrolled between February 2014 and December 2015 into 3 cohorts: cohort 1 = EGFR-positive/ALK-positive disease with ≥ 25% or < 25% programmed cell death ligand 1 (PD-L1) expression on tumor cells (n = 111); cohort 2 = EGFR-negative/ALK-negative disease with ≥ 25% or < 25% PD-L1 expression (n = 265); and cohort 3 = EGFR-negative/ALK-negative disease with ≥ 90% PD-L1 expression (n = 68).
Patients received durvalumab at 10 mg/kg every 2 weeks for up to 12 months, with retreatment allowed for patients who benefited but then had disease progression after completing 12 months of therapy. The primary endpoint was the proportion of patients with PD-L1 expression ≥ 25% in cohorts 1 and 2 and ≥ 90% in cohort 3 who achieved an objective response on Response Evaluation Criteria in Solid Tumors.
Response Rates
Among patients with ≥ 25% PD-L1 expression, objective response was observed in 9 (12.2%) of 74 patients in cohort 1 and 24 (16.4%) of 146 patients in cohort 2. In cohort 3, response was observed in 21 (30.9%) of 68 patients. Response was observed in 3.6% of patients in cohort 1 and 7.5% of those in cohort 2 with PD-L1 expression < 25%. The median duration of response was 7.9 months and 7.4 months in cohort 1 patients with PD-L1 expression ≥ 25% and < 25%, not reached and 12.3 months in cohort 2 patients with PD-L1 expression ≥ 25% and < 25%, and not reached in cohort 3.
Adverse Events
Grade 3 or 4 treatment-related adverse events occurred in 9% of all patients overall, including 5% of cohort 1, 8% of cohort 2, and 18% of cohort 3. The most common treatment-related grade 3 or 4 adverse events were pneumonitis (1%), elevated gamma-glutamyltransferase (1%), diarrhea (1%), and infusion-related reaction (1%). Treatment-related serious adverse events occurred in 6% of patients overall, including 5% of cohort 1, 5% of cohort 2, and 12% of cohort 3. The most common serious adverse events were pneumonitis (1%), fatigue (1%), and infusion-related reaction (1%). The investigators stated that immune-mediated events were manageable using standard treatment guidelines.
The investigators concluded, “In patients with advanced and heavily pretreated NSCLC, the clinical activity and safety profile of durvalumab was consistent with that of other anti–[programmed cell death protein 1 (PD-1)] and anti–PD-L1 agents. Responses were recorded in all cohorts; the proportion of patients with EGFR–/ALK– NSCLC (cohorts 2 and 3) achieving a response was higher than the proportion with EGFR+/ALK+ NSCLC (cohort 1) achieving a response. The clinical activity of durvalumab in patients with EGFR+ NSCLC with ≥ 25% of tumour cells expressing PD-L1 was encouraging…. [T]he results suggest durvalumab might have a role in the treatment of EGFR+ tumours with high PD-L1 expression. Additional prospectively designed controlled studies in patients with EGFR+/ALK+ NSCLC are warranted to further understand the activity of immune checkpoint inhibitors in this population.”
The study was funded by AstraZeneca.
Marina Chiara Garassino, MD, of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, is the corresponding author for The Lancet Oncology article.
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