Avelumab did not improve overall survival compared with docetaxel in patients with PD-L1–positive non–small-cell lung cancer.
The anti–programmed death ligand 1 (PD-L1) agent avelumab did not improve overall survival compared with docetaxel in a phase III trial of patients with PD-L1–positive non–small-cell lung cancer (NSCLC) who had already received platinum-based therapy.
“Antibodies targeting the immune checkpoint molecules PD-1 or PD-L1 improve overall survival compared with standard-of-care chemotherapy in patients with metastatic NSCLC,” wrote study authors led by Fabrice Barlesi, MD, of Aix Marseille University in France. More recent studies have expanded some of those agents’ approvals into earlier NSCLC settings.
The new study compared avelumab, an anti–PD-L1 agent, with docetaxel in patients with stage IIIB or IV NSCLC; all patients had progressed after platinum-based therapy. The results were published in Lancet Oncology.
The JAVELIN Lung 200 study included a total of 792 patients treated at 173 hospitals in 31 countries. They were randomized to receive either avelumab (396 patients, 264 PD-L1–positive tumors) or docetaxel (396 patients, 265 PD-L1–positive tumors); the primary analysis was only of the PD-L1–positive patients. Just over two-thirds of the study population was male, and a similar proportion was white. Approximately 90% of the study participants had received one prior line of therapy.
The median overall survival did not significantly differ between the groups, at 11.4 months with avelumab and 10.3 months with docetaxel, for a hazard ratio (HR) of 0.90 (96% CI, 0.72–1.12; P = .16).
PD-L1 positivity was defined as expression of PD-L1 in at least 1% of tumor cells; when this was adjusted to higher cutoffs, avelumab did have greater efficacy. In patients with at least 50% expression (168 patients in the avelumab group, 147 in the docetaxel group), the median OS was 13.6 months with avelumab and 9.2 months with docetaxel, for an HR of 0.67 (95% CI, 0.51–0.89; P = .0052). At at least 80% expression (120 and 106 patients, respectively), the median OS was 17.1 months and 9.3 months, respectively, for an HR of 0.59 (95% CI, 0.42–0.83).
Grade 3–5 adverse events occurred in 10% of avelumab patients and in 49% of docetaxel patients. With avelumab, the most common such adverse events included infusion-related reactions and increased lipase, while with docetaxel the most common included neutropenia, febrile neutropenia, and decreased neutrophil counts. Serious adverse events were more common with docetaxel, and there were 4 treatment-related deaths with avelumab compared with 14 with docetaxel.
“Overall, although this trial did not meet its primary endpoint, the clinical activity and safety noted in this study support further studies of avelumab in patients with NSCLC,” the authors wrote.
Sameep Sehgal, MD, of Temple University’s Lewis Katz School of Medicine in Philadelphia, who was not involved with the research, said the results “do give us pause,” and that clinicians should remember that not all immune therapeutic agents are the same. “The results may dampen the enthusiasm about using avelumab in advanced lung cancer,” he told Cancer Network, though he pointed out that other studies have shown improved survival with other immunotherapeutic agents. “Improved survival in patients with higher PD-1 expression is encouraging and avelumab may have a role in this subgroup of patients in the future.”