Tumor vaccines, cellular immunotherapies prolong OS, PFS in NSCLC

Tumor vaccines and cellular therapies improved OS and PFS in patients with non–small cell lung cancer, according to results of a meta-analysis.

However, cellular immunotherapy demonstrated greater efficacy than tumor vaccines.

Treatment with PD-1 blockade can effectively treat NSCLC. However, a majority of patients do not respond to checkpoint inhibition therapy, Joachim G. Aerts, MD, PhD, associate professor and chief of the department of thoracic oncology at Erasmus Medical Center, and colleagues wrote.

Tumor vaccines and cellular immunotherapies could synergize with checkpoint blockades, the researchers added.

“Eliciting potent T-cell response via vaccines or cellular therapies and simultaneously releasing the brakes on these T cells with checkpoint inhibitors may unleash the full potential of immunotherapy and improve the proportion of patients responding to therapy,” they added. “Which form of immunotherapy ... is more promising to combine with checkpoint inhibitors such as PD-1 blockers is currently unknown.”

The researchers assessed the efficacy of tumor vaccination and cellular immunotherapy for NSCLC using data culled from 18 randomized control trials composed of 6,756 patients.

Overall, immunotherapy extended median OS by 5.43 months (95% CI, 3.2-7.65) and PFS by 3.24 months (95% CI, 1.61-4.88) in these trials. Immunotherapy also reduced risk for mortality (HR = 0.81; 95% CI, 0.7-0.94) and disease progression (PFS = 0.83; 95% CI, 0.72-0.95).

When evaluated separately, cellular immunotherapeutic strategies improved OS — both in HR calculations (P = .005) and when expressed as median month difference in survival (P = .001) — and PFS for HR (P = .001) and median month difference (P = .004).

The researchers acknowledged these differences could be attributed to possible overrepresentation of phase 2 studies for cellular therapies, as well as to the activation of the immune system with cellular therapies, such as dendritic cell and T-cell therapies.

“Screening patients before vaccination for expression of the targeted tumor antigen and designing personalized tumor vaccines could increase response rates to tumor vaccines,” Aerts and colleagues wrote. “Identifying these patients before or after the first vaccination as personalized therapy could specifically benefit those that are most likely to respond and favor the use of combination treatment in nonresponding patients.”

The researchers also found that the PFS benefit of immunotherapy appeared greater in studies involving low-stage NSCLC compared with high-stage disease when expressed in median month difference (P = .01). Further, studies evaluating the addition of concurrent chemotherapy to immunotherapy demonstrated prolonged time to disease progression (P = .03).

Tumor histology did not demonstrate a significant effect on OS or PFS.

The researchers acknowledged the study may be limited by the number of trials available for some outcome measures investigated, the variability in control treatments with both therapies, and the limited assessment of bias in several trials included.

“Specific immunotherapies significantly prolonged NSCLC survival and PFS,” Aerts and colleagues wrote. “These findings are useful for the design of future studies investigating immunotherapies in NSCLC and possible synergistic combination strategies that could improve patient survival.” – by Kristie L. Kahl

Disclosures: Aerts reports stock and other ownership in Amphera; consulting fees from Bristol-Myers Squibb, Boehringer Ingelheim, Eli-Lilly, Merck and Roche; speakers’ fees from AstraZeneca and Verastem; research funding from Genentech; and patents, royalties and other intellectual property from Tumor cell lysate for dendritic cell loading. The other researchers report no relevant financial disclosures.