Optimal Lymph Node Examination and Adjuvant Chemotherapy for Stage I Lung Cancer

ObjectiveTo determine the optimal number of lymph nodes (LNs) examined and the role of adjuvant chemotherapy in stage I lung cancer.MethodsThe National Cancer Database was queried for surgically treated patients with pathologic stage I lung cancer between 2006 and 2014 (N = 65,438). The optimal LN numbers were determined in the multivariate Cox model and were further validated in the cohort with clinical stage I disease (N = 117,112) in terms of nodal upstaging and prognostic stratification. The role of adjuvant chemotherapy in patients with suboptimal staging (number of LNs examined was less than than the optimum) was evaluated in each T stage.ResultsThe number of LNs examined correlated with tumor size (p < 0.001). There were increasing survival benefits with each additional LN examined—up to eight, nine, 10, and 11 nodes for patients with T1a, T1b, T1c, and T2a, respectively. Validation from the cohort with clinically staged disease showed that the threshold of eight to 11 LNs was an independent predictor of nodal upstaging (OR = 1.706, 95% confidence interval [CI] 1.608–1.779) and survival outcome (hazard ratio = 0.890, 95% CI: 0.865–0.916). After propensity matching, adjuvant chemotherapy was associated with improved survival in patients with stage T2a disease having suboptimal staging (hazard ratio = 0.841, 95% CI: 0.714–0.990), but not in patients with stage T1a to T1c disease.ConclusionLN evaluation was important for accurate staging and adequate treatment, and examinations of an increasing number of nodes for progressively higher T components (i.e., eight, nine, 10, and 11 nodes for T1a, T1b, T1c, and T2a tumors, respectively) seemed crucial to predict upstaging and survival outcomes. Adjuvant chemotherapy might be beneficial to patients with stage T2a disease who have suboptimal nodal staging.     

Spread Through Air Spaces (STAS) Is Prognostic in Atypical Carcinoid,Large Cell Neuroendocrine Carcinoma,and Small Cell Carcinoma of the Lung

IntroductionTumor spread through air spaces (STAS) has prognostic significance in lung adenocarcinoma and squamous cell carcinoma. We sought to investigate the prognostic importance of STAS in lung neuroendocrine tumors (NETs).MethodsAll tumor slides from patients with resected pathologic stage I to III lung NETs (N = 487) (299 with typical carcinoid [TC], 38 with atypical carcinoid [AC], 93 with large cell neuroendocrine carcinoma [LCNEC], and 57 with SCLC) treated between 1992 and 2012 were evaluated for presence of STAS. Cumulative incidence of recurrence (CIR) and lung cancer–specific cumulative incidence of death (LC-CID) were analyzed by using a competing-risks approach.ResultsSTAS was identified in 26% of NETs (16% of TCs, 37% of ACs, 43% of LCNECs, and 46% of SCLCs). STAS was associated with distant metastasis, as well as with higher CIR and LC-CID in the overall cohort and in the AC, LCNEC, and SCLC cohorts (owing to a small number of recurrences and deaths [<5], prognostic analysis was not performed in the TC cohort). In multivariable analysis stratified by stage, STAS was significantly associated with higher CIR (subhazard ratio = 2.85, 95% confidence interval: 1.73–4.68, p < 0.001) and LC-CID (subhazard ratio = 2.72, 95% confidence interval: 1.57–4.70, p < 0.001), independent of histologic subtype. STAS was independently associated with CIR and LC-CID in the LCNEC cohort and LC-CID in the SCLC cohort.ConclusionsIn patients with lung NETs, STAS is associated with early distant metastasis and worse LC-CID. In patients with LCNEC or SCLC, STAS is an independent poor prognostic factor.     

Association of Early Palliative Care With Chemotherapy Intensity in Patients With Advanced Stage Lung Cancer: A National Cohort Study

Introduction

Patients with advanced lung cancer have a poor prognosis, but both chemotherapy and early palliative care (EPC) have been shown to improve survival and quality of life (QOL). The relationship between palliative care and receipt of chemotherapy receipt is understudied. We sought to determine if EPC is associated with chemotherapy receipt and intensity among patients with advanced stage lung cancer.

MET IHC Is a Poor Screen for MET Amplification or MET Exon 14 Mutations in Lung Adenocarcinomas: Data from a Tri-Institutional Cohort of the Lung Cancer Mutation Consortium

IntroductionMNNG HOS Transforming gene (MET) amplification and MET exon 14 (METex14) alterations in lung cancers affect sensitivity to MET proto-oncogene, receptor tyrosine kinase (MET [also known by the alias hepatocyte growth factor receptor]) inhibitors. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and immunohistochemistry (IHC) have been used to evaluate MET dependency. Here, we have determined the association of MET IHC with METex14 mutations and MET amplification.MethodsWe collected data on a tri-institutional cohort from the Lung Cancer Mutation Consortium. All patients had metastatic lung adenocarcinomas and no prior targeted therapies. MET IHC positivity was defined by an H-score of 200 or higher using SP44 antibody. MET amplification was defined by copy number fold change of 1.8x or more with use of NGS or a MET-to–centromere of chromosome 7 ratio greater than 2.2 with use of FISH.ResultsWe tested tissue from 181 patients for MET IHC, MET amplification, and METex14 mutations. Overall, 71 of 181 patients (39%) were MET IHC–positive, three of 181 (2%) were MET-amplified, and two of 181 (1%) harbored METex14 mutations. Of the MET-amplified cases, two were FISH positive with MET-to–centromere of chromosome 7 ratios of 3.1 and 3.3, one case was NGS positive with a fold change of 4.4x, and one of the three cases was MET IHC–positive. Of the 71 IHC-positive cases, one (1%) was MET-amplified and two (3%) were METex14-mutated. Of the MET IHC–negative cases, two of 110 (2%) were MET-amplified.ConclusionsIn this study, nearly all MET IHC–positive cases were negative for MET amplification or METex14 mutations. MET IHC can also miss patients with MET amplification. The limited number of MET-amplified cases in this cohort makes it challenging to demonstrate an association between MET IHC and MET amplification. Nevertheless, IHC appears to be an inefficient screen for these genomic changes. MET amplification or METex14 mutations can best be detected by FISH and a multiplex NGS panel.     

Population-Based Relative Risks for Lung Cancer Based on Complete Family History of Lung Cancer

IntroductionPublished risk estimates for diagnosis of lung cancer based on family history are typically focused on close relatives, rather than a more diverse or complete family history. This study provides estimates of relative risk (RR) for lung cancer based on comprehensive family history data obtained from a statewide cancer registry linked to a high-quality genealogy data resource that is extensive and deep. The risk estimates presented avoid common recall, recruitment, ascertainment biases, and are based on an individual’s (proband’s) lung cancer family history constellation (pattern of lung cancer affected relatives); numerous constellations are explored.MethodsWe used a population-based genealogic resource linked to a statewide electronic Surveillance Epidemiology and End Results program cancer registry to estimate RR for lung cancer for an individual based on their lung cancer family history. The family history data available for a proband included degree of relationship (first- to third-degree), paternal or maternal family lung cancer history, number of lung cancer–affected relatives, and age at diagnosis of affected relatives. More than 1.3 million probands with specific constellations of lung cancer were analyzed. To estimate RRs for lung cancer, the observed number of lung cancer cases among probands with a specific family history constellation was compared to the expected number using internal cohort-specific rates.ResultsA total of 5048 lung cancer cases were identified. Significantly elevated RR was observed for any number of lung cancer–affected relatives among first-, second-, or third-degree relatives. RRs for lung cancer were significantly elevated for each additional lung cancer first-degree relative (FDR) ranging from RR = 2.57 (confidence interval [CI] 95%: 2.39, 2.76) for 1 or more FDR to RR = 4.24 (CI 95%: 1.56, 9.23) for 3 or more FDRs affected. In an absence of FDR family history, increased risk for lung cancer was significant for increasing numbers of affected second-degree relatives (SDRs) ranging from 1.41 (CI 95%: 1.30, 1.52) for 1 or more SDRs to 4.76 (CI 95%: 1.55, 11.11) for 4 or more SDRs. In the absence of affected FDRs and SDRs, there were significantly increased risks based on lung cancer–affected third-degree relatives (TDRs) ranging from 1.18 (CI 95%: 1.11, 1.24) for 1 or more affected TDRs to 1.55 (CI 95%: 1.03, 2.24) for 4 or more affected TDRs. RRs were significantly increased with earlier age at diagnosis of a FDR, and equivalent risks for maternal compared to paternal history were observed.ConclusionsThis study provides population-based estimates of lung cancer risk based on a proband’s complete family history (lung cancer constellation). Many individuals at two to five or more times increased risk for lung cancer are identified. Estimates of RR for lung cancer based on family history are arguably relevant clinically. The constellation RR estimates presented could serve in individual decision-making to direct resource use for lung cancer screening, and could be pivotal in decision-making for screening, treatment, and post-treatment surveillance.     

Safety,Efficacy, and Patient-Reported Health-Related Quality of Life and Symptom Burden with Nivolumab in Patients with Advanced Non–Small Cell Lung Cancer,Including Patients Aged 70 Years or Older or with Poor Performance Status (CheckMate 153)

IntroductionCheckMate 153 (NCT02066636) is a phase 3B/4 study assessing nivolumab in previously treated patients with advanced NSCLC. Eligibility criteria allowed enrollment of patients with poor prognostic features of advanced age or diminished Eastern Cooperative Oncology Group performance status (ECOG PS), which are typically underrepresented in or excluded from randomized controlled trials.MethodsPatients with stage IIIB or IV NSCLC and an ECOG PS of 0 to 2 with disease progression after at least one systemic therapy received nivolumab (3 mg/kg every 2 weeks) until progression, unacceptable toxicity, or consent withdrawal. The primary end point was the incidence of grade 3 to 5 select treatment-related adverse events (TRAEs).ResultsAmong 1426 treated patients, 556 (39%) were aged 70 years or older and 128 (9%) had an ECOG PS of 2. The median treatment duration was 3.2 months. Across subgroups and the overall population, the incidences of select grade 3 to 5 TRAEs (6%–9%) and grade 3 or 4 TRAEs (12%–14%) were similar. One grade 5 TRAE was documented. The median overall survival time was comparable in the overall population (9.1 months) and patients aged 70 years or older (10.3 months) but shorter in patients with an ECOG PS of 2 (4.0 months). Patient-reported outcomes generally improved.ConclusionsData from this large predominantly community-based study, which included patients aged 70 years or older and with an ECOG PS of 2, are consistent with registrational studies. As expected, the median overall survival for patients with an ECOG PS of 2 was lower than for the overall population but comparable with historical data.     

Recurrently Mutated Genes Differ between Leptomeningeal and Solid Lung Cancer Brain Metastases

When compared with solid brain metastases from NSCLC, leptomeningeal disease (LMD) has unique growth patterns and is rapidly fatal. Patients with LMD do not undergo surgical resection, limiting the tissue available for scientific research. In this study we performed whole exome sequencing on eight samples of LMD to identify somatic mutations and compared the results with those for 26 solid brain metastases. We found that taste 2 receptor member 31 gene (TAS2R31) and phosphodiesterase 4D interacting protein gene (PDE4DIP) were recurrently mutated among LMD samples, suggesting involvement in LMD progression. Together with a retrospective review of the charts of an additional 44 patients with NSCLC LMD, we discovered a surprisingly low number of KRAS mutations (n = 4 [7.7%]) but a high number of EGFR mutations (n = 33 [63.5%]). The median interval for development of LMD from NSCLC was shorter in patients with mutant EGFR (16.3 months) than in patients with wild-type EGFR (23.9 months) (p = 0.017). Targeted analysis of recurrent mutations thus presents a useful complement to the existing diagnostic tool kit, and correlations of EGFR in LMD and KRAS in solid metastases suggest that molecular distinctions or systemic treatment pressure underpin the differences in growth patterns within the brain.     

Circulating Inflammation Proteins Associated With Lung Cancer in African Americans

IntroductionLung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) in the United States. We and others have previously shown a relationship between immune and inflammation proteins with lung cancer in EAs. Our aim was to investigate the etiologic relationship between inflammation and lung cancer in AAs.MethodsWe adopted a two-stage, independent study design (discovery cases, n = 316; control cases, n = 509) (validation cases, n = 399; control cases, n = 400 controls) and measured 30 inflammation proteins in blood using Meso Scale Discovery V- PLEX multiplex assays.ResultsWe identified and validated 10 proteins associated with lung cancer in AAS, some that were common between EAs and AAs (C-reactive proteins [OR: 2.90; 95% confidence interval (CI): 1.99–4.22], interferon γ [OR: 1.55; 95% CI: 1.10–2.19], interleukin 6 [OR: 6.28; 95% CI: 4.10–9.63], interleukin 8 [OR: 2.76; 95% CI: 1.92–3.98]) and some that are only observed among AAs (interleukin 10 [OR: 1.69; 95% CI: 1.20–2.38], interleukin 15 [OR: 2.83; 95% CI: 1.96–4.07], interferon gamma-induced protein 10 [OR: 1.54; 95% CI: 1.09–2.18], monocyte chemotactic protein-4 [OR: 0.54; 95% CI: 0.38–0.76], macrophage inflammatory protein-1 alpha [OR: 1.57; 95% CI: 1.12–2.21], and tumor necrosis factor β [OR: 0.52; 95% CI: 0.37–0.74]). We did not find evidence that either menthol cigarette smoking or global genetic ancestry drove these population differences.ConclusionsOur results highlight a distinct inflammation profile associated with lung cancer in AAs compared with EAs. These data provide new insight into the etiology of lung cancer in AAs. Further work is needed to understand what drives this relationship with lung cancer and whether these proteins have utility in the setting of early diagnosis.     

Updated Efficacy and Safety Data and Impact of the EML4-ALK Fusion Variant on the Efficacy of Alectinib in Untreated ALK-Positive Advanced Non–Small Cell Lung Cancer in the Global Phase III ALEX Study

IntroductionAt the prior data cutoff (February 9, 2017) the ALEX trial showed superior investigator-assessed progression-free survival (PFS) for alectinib versus crizotinib in untreated, anaplastic lymphoma kinase (ALK)-positive, advanced NSCLC (hazard ratio = 0.47, 95% confidence interval: 0.34–0.65, p < 0.001). The median PFS in the alectinib arm was not reached versus 11.1 months with crizotinib. Retrospective analyses suggest that the echinoderm microtubule-associated protein-like 4 gene-ALK variant (EML4-ALK) may influence ALK-inhibitor treatment benefit. We present updated analyses, including exploratory subgroup analysis by EML4-ALK variant, after an additional 10 months’ follow-up (cutoff December 1, 2017).MethodsPatients were randomized to receive twice-daily alectinib, 600 mg, or crizotinib, 250 mg, until disease progression, toxicity, death, or withdrawal. PFS was determined by the investigators. Baseline plasma and tissue biomarker samples were analyzed by using hybrid-capture, next-generation sequencing to determine EML4-ALK variant.ResultsBaseline characteristics were balanced. Investigator-assessed PFS was prolonged with alectinib (stratified hazard ratio = 0.43, 95% confidence interval: 0.32–0.58). The median PFS times were 34.8 months with alectinib and 10.9 months with crizotinib. EML4-ALK fusions were detectable in 129 patient plasma samples and 124 tissue samples; variants 1, 2, and 3/ab did not affect PFS, objective response rate, or duration of response. Investigator-assessed PFS was longer for alectinib than for crizotinib across EML4-ALK variants 1, 2, and 3a/b in plasma and tissue. Despite longer treatment duration (27.0 months in the case of alectinib versus 10.8 months in the case of crizotinib), the safety of alectinib compared favorably with that of crizotinib.ConclusionAlectinib continues to demonstrate superior investigator-assessed PFS versus crizotinib in untreated ALK-positive NSCLC, irrespective of EML4-ALK variant.     

Radiologic Criteria in Predicting Pathologic Less Invasive Lung Cancer According to TNM 8th Edition

PurposeThe Japan Clinical Oncology Group Study 0201 has proposed radiologic criteria on thin-slice computed tomography to diagnose pathologic less invasive lung adenocarcinoma that could be a candidate for sublobar resection based on the previous tumor, node, metastasis classification system (TNM). The aim of this study was to propose the new radiologic criteria for predicting pathologic less invasive cancer according to the 8th edition TNM.Patients and MethodsWe analyzed 744 patients who had peripheral clinical Tis-T1cN0M0 non–small-cell lung cancer of 3 cm or less and underwent complete resection by lobectomy from 2003 to 2011. We defined lung cancer with no nodal involvement and no vessel invasion pathologically as a pathologic less invasive cancer and investigated the radiologic criteria on the basis of the solid component size and by the consolidation-to-tumor (C/T) ratio (calculated with the maximum solid component diameter divided by the maximum tumor diameter) by using preoperative thin-slice computed tomography to predict them with a specificity of 97% or more, and evaluated overall survival.ResultsPatients with clinical Tis/T1mi/T1a disease had no pathologic invasive cancer except for one patient (specificity, 99%). From the investigation with the C/T ratio, only the criterion of C/T ratio 0.5 or less met the standard (specificity, 100%). The final specificity after combining these criteria was 99.6%, and they showed excellent prognosis (5-year overall survival rate, 96.2%).ConclusionLung cancer with clinical Tis/T1mi/T1a or a C/T ratio of 0.5 or less can be completely cured by sublobar resection with sufficient margin because of its less invasive nature pathologically.     

Postoperative Recurrence and Survival After Segmentectomy for Clinical Stage 0 or IA Lung Cancer

BackgroundAlthough radical segmentectomy is an accepted treatment option for small-sized lung cancer, the outcomes remain unclear. The present study aimed to elucidate recurrence patterns and to identify predictors of time to recurrence after intentional segmentectomy for early lung cancer.Patients and MethodsProspectively collected data of 166 patients who could tolerate lobectomy and underwent intentional segmentectomy for clinical stage 0 or IA non–small-cell lung cancer between 2007 and 2016 were retrospectively analyzed. Surgical indication for intentional segmentectomy was clinical stage 0 or IA ground glass opacity-dominant tumor ≤ 3 cm or solid-dominant tumor ≤ 2 cm on high-resolution computed tomography.ResultsThe median follow-up duration was 48.8 months, during which 6 (3.6%) patients developed recurrences. The 5-year recurrence-free survival and 5-year overall survival rates were 93.1% (95% confidence interval [CI], 87.9%-96.1%) and 93.5% (95% CI, 87.7%-96.4%), respectively. Two (1.2%) patients who developed local-only recurrences subsequently underwent completion lobectomy; no cancer-related deaths were seen for these patients. In multivariable analysis, consolidation to maximum tumor diameter (C/T) ratio (hazard ratio, 1.07; 95% CI, 1.01-1.22; P = .02) was an independent predictive factor for time to recurrence. All 6 patients with recurrence had a tumor with a C/T ratio of 86% or higher.ConclusionsBased on these findings, favorable survival is expected after intentional segmentectomy for selected patients with clinical stage 0 or IA non–small-cell lung cancer. Patients with a higher C/T ratio tumor appear to be at higher risk of recurrence after intentional segmentectomy.     

Spread Through Air Spaces (STAS): A New Pathologic Morphology in Lung Cancer

In 2015, the World Health Organization classification of lung cancer proposed the concept of spread through air spaces (STAS) as a new pattern of invasion in lung adenocarcinoma. The definition of STAS included one or more pathologic micropapillary clusters, solid nests or single cells beyond the edge of the tumor into air spaces in the surrounding lung parenchyma, and separation from the main tumor other than tumor islands. The roles of STAS has been investigated in many studies. The results indicated that STAS is associated with key clinical variables and the prognosis of patients both in lung adenocarcinoma, lung squamous cell carcinoma, small-cell lung cancer, and lung pleomorphic carcinoma. This mini review will be focused on the developments and perspectives of STAS in lung cancer.     

Cost-Effectiveness of Web-Based Patient-Reported Outcome Surveillance in Patients With Lung Cancer

IntroductionA multicenter randomized clinical trial in France found an overall survival benefit of web-based patient-reported outcome (PRO)–based surveillance after initial treatment for lung cancer compared with conventional surveillance. The aim of this study was to assess the cost-effectiveness of this PRO-based surveillance in lung cancer patients.MethodsThis medico-economic analysis used data from the clinical trial, augmented by abstracted chart data and costs of consultations, imaging, transportations, information technology, and treatments. Costs were calculated based on actual reimbursement rates in France, and health utilities were estimated based on scientific literature review. Willingness-to-pay thresholds of €30,000 per quality-adjusted life year (QALY) and €90,000 per QALY were used to define a very cost-effective and cost-effective strategy, respectively. Average annual costs of experimental and control surveillance approaches were calculated. The incremental cost-effectiveness ratio was expressed as cost per life-year gained and QALY gained, from the health insurance payer perspective. One-way and multivariate probabilistic sensitivity analyses were performed.ResultsAverage annual cost of surveillance follow-up was €362 lower per patient in the PRO arm (€941/year/patient) compared to control (€1,304/year/patient). The PRO approach presented an incremental cost-effectiveness ratio of €12,127 per life-year gained and €20,912 per QALY gained. The probabilities that the experimental strategy is very cost-effective and cost-effective were 97% and 100%, respectively.ConclusionsSurveillance of lung cancer patients using web-based PRO reduced the follow-up costs. Compared to conventional monitoring, this surveillance modality represents a cost-effective strategy and should be considered in cancer care delivery.     

Pemetrexed in the Treatment of Leptomeningeal Metastasis in Patients With EGFR-mutant Lung Cancer

IntroductionLeptomeningeal metastasis (LM), still an area of unmet need, has frequently been observed in patients with EGFR-mutant non–small-cell lung cancer (NSCLC). Because the antitumor efficacy of systemic cytotoxic agents against LM is unclear, we explored the role of pemetrexed in the treatment of patients with LM from EGFR-mutant NSCLC.Patients and MethodsWe retrospectively reviewed the medical records of patients with LM from EGFR-mutant NSCLC treated between 2006 and 2016. Post-LM survival was evaluated as well as clinical factors.ResultsIn our patient cohort with EGFR-mutant NSCLC (n = 631), 17.4% (n = 110) developed LM. Their median post-LM survival was 5.7 months (95% confidence interval, [CI], 0.0-12.0 months). Post-LM survival was significantly longer with pemetrexed use after LM (median, 13.7 months; 95% CI, 4.1-23.2 months) than without pemetrexed use after LM (median, 4.0 months; 95% CI, 2.2-5.7 months; P = .008). In the multivariate analyses, no pemetrexed use after LM (vs. use) and no EGFR tyrosine kinase inhibitor use after LM (vs. use) were independently associated with a poor post-LM survival with a hazard ratio of 3.1 (95% CI, 1.5-6.3; P = .002) and 3.0 (95% CI, 1.6-5.8; P = .001), respectively.ConclusionPemetrexed use after LM was independently associated with a longer post-LM survival in patients with EGFR-mutant NSCLC with LM. Prospective studies are warranted to validate this finding.     

Efficacy of Immune Checkpoint Inhibitors in KRAS-Mutant Non-Small Cell Lung Cancer (NSCLC)

IntroductionKRAS mutation is the most frequent molecular alteration found in advanced NSCLC; it is associated with a poor prognosis without available targeted therapy. Treatment options for NSCLC have been recently enriched by the development of immune checkpoint inhibitors (ICIs), and data about its efficacy in patients with KRAS-mutant NSCLC are discordant. This study assessed the routine efficacy of ICIs in advanced KRAS-mutant NSCLC.MethodsIn this retrospective study, clinical data were extracted from the medical records of patients with advanced NSCLC treated with ICIs and with available molecular analysis between April 2013 and June 2017. Analysis of programmed death ligand 1 (PD-L1) expression was performed if exploitable tumor material was available.ResultsA total of 282 patients with ICI-treated (in the first line or more) advanced NSCLC (all histological subgroups) who were treated with ICIs (anti–programmed death 1, anti–PD-L1, or anti–cytotoxic T-lymphocyte associated protein 4 antibodies), including 162 (57.4%) with KRAS mutation, 27 (9.6%) with other mutations, and 93 (33%) with a wild-type phenotype, were identified. PD-L1 analysis was available for 128 patients (45.4%), of whom 45.3% and 19.5% had PD-L1 expression of 1% or more and 50%, respectively (49.5% and 21.2%, respectively, in the case of the 85 patients with KRAS-mutant NSCLC). No significant difference was seen in terms of objective response rates, progression-free survival, or overall survival between KRAS-mutant NSCLC and other NSCLC. No significant differences in overall survival or progression-free survival were observed between the major KRAS mutation subtypes (G12A, G12C, G12D, G12V, and G13C). In KRAS-mutant NSCLC, unlike in non–KRAS-mutant NSCLC, the efficacy of ICIs is consistently higher, even though not statistically significant, for patients with PD-L1 expression in 1% or more of tumor cells than for those with PD-L1 expression in less than 1% of tumor cells, and this finding is especially true when PD-L1 expression is high (PD-L1 expression ≥50%).ConclusionFor patients with KRAS-mutant NSCLC (all mutational subtypes), the efficacy of ICI is similar to that for patients with other types of NSCLC. PD-L1 expression seems to be more relevant for predicting the efficacy of ICIs in KRAS-mutant NSCLC than it is in other types of NSCLC.