Chemoimmunotherapy Tied to Better Outcomes in Advanced NSCLC

Patients with advanced non-small cell lung cancer (NSCLC) and PD-L1 scores 1%-49% who received chemoimmunotherapy regimens seemed to do better than patients treated with immunotherapy alone, according to an exploratory pooled analysis.

Median overall survival (OS) among patients treated with FDA-approved immunotherapy agents was 14.5 months versus a median OS of 21.4 months for patients given chemoimmunotherapy (HR 0.68, 95% CI 0.52-0.90). Median progression-free survival (PFS) was 4.2 months versus 7.78, respectively (HR 0.68, 95% CI 0.52-0.90), reported Oladimeji Akinboro, MD, of the FDA Center for Drug Evaluation and Research in Silver Spring, Maryland, at the American Society of Clinical Oncology virtual meeting.

Akinboro acknowledged that the results were limited by the study designed, which compared results across clinical trials — an often-used method that is statistically challenged. “These results are hypothesis generating,” he stressed, nothing that just two trials in the analysis evaluated immunotherapy alone while six trials looked at chemoimmunotherapy.

In addition, “clinical trials do not reflect real-world patients treated with FDA-approved regimens,” he stated.

Nonetheless, “FDA-approved chemotherapy-immunotherapy regimens may improve OS and PFS compared with immunotherapy-only regimens in most subgroups of patients including adults aged 65-74 years, and in adults with ECOG performance status of 1,” according to Akinboro and colleagues.

However, patients ages ≥75 did not see substantial benefits with either single or combined regimens, although “there is no evidence that older adults have worse outcomes with chemotherapy-immunotherapy regimens compared with immunotherapy alone,” Akinboro noted.

Mary Redman, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, said the findings should lead to a prospective study that would compare immunotherapy alone, chemoimmunotherapy, and chemotherapy alone.

Redman, who was not involved in the study, said she had concerns about the data pooling. “Doing these kinds of analyses are quite important because it allows us to be able to interpret what are future questions,” she stated, but “I think the key is that we shouldn’t use these analyses to be definitive,” and agreed that they should be hypothesis-generating.

Akinboro and colleagues identified patients with advanced NSCLC with PD-L1 expressing tumors and who did not have sensitizing EGFR mutations or ALK alterations.

The immunotherapy-only patients were identified from the KEYNOTE-042 trial with pembrolizumab (Keytruda), and the CHECKMATE-227 trial of nivolumab (Opdivo) plus ipilimumab (Yervoy). Chemoimmunotherapy trials looked at mostly platinum-based regimens paired with pembrolizumab, atezolizumab (Tecentriq), and nivolumab-ipilimumab.

Akinboro’s group analyzed outcomes of 639 patients who received chemoimmunotherapy and 529 patients treated with immunotherapy alone. The combination therapy group included a higher percentage of women, of whites, and of people with a smoking history. About half the patients were ages <65.