The effectiveness of smoking cessation in patients with non-small cell lung cancer is not inferior to the effectiveness of innovative immunotherapy

Introduction. Smoking not only causes cancer but also worsens the prognosis of cancer patients. 
Objective. To compare the effects of smoking cessation with the efficacy of FDA-approved immune checkpoint inhibitors (ICIs).
Materials and Methods. A cohort of 1,240 patients diagnosed with non-small cell lung cancer (NSCLC) (stages I–IIIa) treated from 2007 to 2016 was followed until 2021. Published results of randomized clinical trials (RCTs) evaluating the efficacy of FDA-approved ICIs were analyzed. Overall survival (OS), progression-free survival (PFS), and NSCLC-specific mortality, along with the corresponding hazard ratios (HRs), were calculated. OS and PFS were compared between NSCLC patients who quit smoking and those who received ICIs.
Results. In a cohort of 521 patients who smoked at diagnosis, adjusted median OS and PFS were 21.6 months longer in patients who quit smoking than in patients who continued smoking (6.6 vs. 4.8 years, p = 0.001; 5.7 vs. 3.9 years, p = 0.004). Smoking cessation is associated with a reduced risk of all-cause mortality (HR = 0.67 [95 % CI 0.53–0.85]), lung cancer progression (HR = 0.70 [95 % CI 0.56–0.89]), and lung cancer-specific mortality (HR = 0.75 [95 % CI 0.58–0.98]). The median PFS benefit of 21.6 months from smoking cessation exceeds the benefit achieved with nivolumab in combination with chemotherapy, which is 10.8 months (RCT CheckMate 816), and with pembrolizumab in the adjuvant setting, which is 16.6 months (PEARLS / KEYNOTE-091). A 30 % (HR = 0.70) reduction in the risk of progression resulting from smoking cessation is comparable to a 37 % (HR = 0.63) reduction in the risk associated with nivolumab in combination with chemotherapy in the neoadjuvant setting and a 24 % (HR = 0.76) reduction in the risk associated with pembrolizumab in the adjuvant setting. A 42 % (HR = 0.58) risk reduction (KEYNOTE-671 RCT) resulting from perioperative use of pembrolizumab exceeds the PFS benefit of smoking cessation. Overall, the benefit of smoking cessation is not inferior to that associated with the use of ICIs in patients diagnosed with NSCLC. The effectiveness of smoking cessation is virtually universal and is not limited by any clinical parameters, unlike ICIs, whose effectiveness is limited to certain clinical subgroups, particularly PD-L1‑positive tumors. The absence of adverse side effects also supports smoking cessation.
Conclusion. Smoking cessation should be a critical component of medical care for cancer patients. This will improve the effectiveness of all anticancer treatments, including surgery, medication, and radiation therapy.

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