Immune-Related Side Effects Associated With Improved Survival in NSCLC

Immune checkpoint inhibitor therapy was associated with improved overall survival in patients with metastatic non-small cell lung cancer.

Among patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who receive treatment via immune checkpoint inhibitor (ICI) therapy, the development of immune-related side effects has been found by researchers to be associated with improved overall survival (OS; the time that a patient lives following treatment, regardless of disease status).

“Developing an immune-related (side effect) mandating delay or discontinuation of ICI therapy and/or systemic corticosteroids for management of toxic effects was associated with significantly improved median overall survival,” researchers wrote in a study published in JAMA Network Open. “This association was not compromised by hospitalization for management of toxic effects of severe immune-related adverse events.”

Analyzing data from 803 patients with NSCLC who received ICIs between March 1, 2014 and Nov. 30, 2021 in Alberta, Canada captured via the Alberta Immunotherapy Database with median ages of 69.7 and 67.5 and sex distribution of 52.9% women and 49.7% women for patients who did and did not experience immune-related side effects, respectively, researchers found that the median OS for the total study cohort was 15.7 months.

“In the 12-week landmark analysis (of 611 patients),” researchers noted, “developing a clinically meaningful (immune-related side effect) was associated with a significantly longer median OS compared with those patients who did not,” with median OS findings of 23.7 versus 9.8 months, according to the study.

The same analysis found that the development of a clinically meaningful immune-related side effect was associated with a median time of 18 months to the next treatment, compared with 7.3 months until the next treatment for patients who did not experience such a side effect.

Researchers reported that 297 patients were diagnosed with a clinically meaningful immune-related side effect, meaning a side effect that caused a delay in or discontinuation of ICI therapy and/or systematic steroids to manage toxic effects, with a median time to development of 3.4 months and the most common being pneumonitis (inflammation in the lungs, 82 patients), dermatitis (skin swelling and irritation, 63 patients) and colitis (inflammation in the colon, 42 patients).

Additionally, researchers noted the relative frequency of immune-related side effects by type of ICI, with 196 of 509 patients (38.5%) treated with Keytruda (pembrolizumab), 99 of 280 (35.4%) treated with Opdivo (nivolumab), one of nine (11.1%) who received Tecentriq (atezolizumab) and 20 of 62 (32.3%) for an ICI combined with chemotherapy. Ninety of 297 patients, or 30.3%, were hospitalized due to the side effects, with 47 of the hospitalized cases, or 52.2%, due to pneumonitis.

Researchers stated that their study was “the largest contemporary clinical dataset examining (immune-related side effects) and survival in locally advanced or metastatic NSCLC.”

“In our cohort, we identified several baseline patient characteristics associated with (immune-related side effect) development: (patients who were) 60 years or older, ECOG performance status 0 (meaning they had no difficulty performing daily tasks independently), high expression of (the protein) PD-L1, absence of bone metastases, DNLR (derived neutrophil-lymphocyte ratio) of 3 or less, and levels of hemoglobin, albumin and LDH (lactate dehydrogenase) within reference range,” researchers wrote. “Other than response to ICI therapy, (immune-related side effect) development was not associated with treatment-related characteristics ([including] ICI agent, ICI alone or in combination with chemotherapy, and treatment line) in our study population.”

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