Clinical activity of programmed cell death 1 (PD-1) blockade in never, light, and heavy smokers with non-small-cell lung cancer and PD-L1 expression ≥50%

Abstract

Background: Immune checkpoint inhibitors (ICIs) are standard therapies for patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. Tumor mutation burden (TMB) also predicts response to ICIs but is often not available in real time for decision making in the first-line setting. Smoking exposure can be a proxy for TMB in NSCLC. The impact of smoking status on efficacy of PD-1 blockade in NSCLC patients with PD-L1 TPS ≥50% has not been well defined. Patients and methods: To investigate the relationship between smoking and activity of ICIs in NSCLC, we retrospectively studied 315 patients with NSCLC and PD-L1 TPS ≥50% at five USA academic medical centers. Objective response rates (ORRs), progression-free survival (PFS), and duration of response (DOR) were compared between never (<100 lifetime cigarettes), light (≤10 pack-years), and heavy (>10 pack-years) smokers. A subset of patients underwent next-generation sequencing to estimate TMB. Results: We identified 36 (11%) never, 42 (13%) light, and 237 (75%) heavy smokers with NSCLC and PD-L1 TPS ≥50% treated with ICIs. Objective responses were observed in 27%, 40%, and 40% of never, light, and heavy smokers, respectively ( P = 0.180 never versus heavy; P = 1.000 light versus heavy). Median PFS and median DOR were numerically shorter in never and light smokers compared with heavy smokers (PFS 3.0 versus 4.0 versus 5.4 months; median DOR 6.9 versus 10.8 versus 17.8 months), but were not statistically different [PFS: hazard ratio (HR) 1.37, P = 0.135 and HR 1.24, P = 0.272; DOR: HR 1.92, P = 0.217 and HR 1.79, P = 0.141]. Conclusions: PD-(L)1 inhibitors are associated with antitumor activity in NSCLC with PD-L1 TPS ≥50% regardless of smoking status. Nevertheless, there is a signal of potentially decreased durability among never and light smokers that should be further evaluated. Distinct immunobiologic features may affect initial response versus durability of antitumor immunity to programmed cell death 1 (PD-1) blockade.

Using deep learning to predict anti-PD-1 response in melanoma and lung cancer patients from histopathology images

“…Past research has shown that tumor mutation burden (TMB), microsatellite instability (MSI) and PD-L1 expression may predict ICB response in some cancer types [6] , [7] , [8] . However, no biomarker is currently validated to predict resistance or benefit derived from immunotherapy with clinically significant accuracy.…”

WITHDRAWN: Correlation between DVH parameters and lung function changes before and after radiotherapy and the occurrence of radiation-induced lung injury (RILI)

“…pneumonitis, but recent studies have found that the occurrence of radiation pneumonitis is also related to the lung function before radiotherapy [16,17]. The incidence of chest cancer treated with radiotherapy and chemotherapy is 40-60% [18,19]. Due to its high incidence, insidious onset, delayed onset, and no targeted treatment, once diagnosed, it is often impossible to reverse the condition.…”

Exploration of the role of tumor mutation burden in clinical significance, immunotherapy response predictor and immune cell infiltration in colon cancer

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