Survival trends among patients with metastatic non-small cell lung cancer before and after the approval of immunotherapy in the United States: A Surveillance, Epidemiology, and End Results database-based study.

BACKGROUND: In 2015, the US Food and Drug Administration approved nivolumab as the first immunotherapy for patients with advanced non-small cell lung cancer (NSCLC). However, population-based survival benefit studies after the introduction of immunotherapy in lung cancer are lacking. This study examined overall survival (OS) and cancer-specific survival in patients with NSCLC in the pre immunotherapy and immunotherapy eras. METHODS: This study used the Surveillance, Epidemiology, and End Results database, which spanned 17 registries from 2000 to 2020. Two cohorts were delineated: preimmunotherapy (2010-2014) and immunotherapy (2015-2020), which coincided with nivolumab's approval. RESULTS: This study included 191,802 patients, 90,807 in the preimmunotherapy era and 100,995 in the immunotherapy era. OS was significantly higher in the immunotherapy era, as shown by Kaplan-Meier curves (1-year OS, 40.1% vs. 33.5%; 3-year OS, 17.8% vs. 11.7%; 5-year OS, 10.7% vs. 6.8%; median OS, 8 vs. 7 months; p < .001 by log-rank test). Similarly, cancer-specific survival improved in the immunotherapy era (1-year survival, 44.0% vs. 36.8%; 3-year survival, 21.7% vs. 14.4%; 5-year survival, 14.3% vs. 9.0%; median OS, 10 vs. 8 months; p < .001 by log-rank test). Survival rates were significantly better in the immunotherapy era, as confirmed by multivariate analysis with a Cox proportional hazards model after adjusting for age, sex, race, income, and geographical area (adjusted hazard ratio, 0.830; 95% CI, 0.821-0.840; p < .001). CONCLUSIONS: In summary, the survival rate of patients with metastatic NSCLC has improved since the introduction of immunotherapy.

Efficacy and adverse events of five targeted agents in the treatment of advanced or metastatic non-small-cell lung cancer: A network meta-analysis of nine eligible randomized controlled trials involving 5,059 patients.

Recently, targeted agents were reported to improve overall survival, progression-free survival (PFS), response rate, and quality of life compared with cytotoxic chemotherapies, which provides hope for the treatment of non-small-cell lung cancer (NSCLC). The network meta-analysis is applied to compare the efficacies and adverse events of five targeted agents (erlotinib, gefitinib, vandetanib, dacomitinib, and icotinib) for advanced or metastatic NSCLC. Nine eligible randomized controlled trials from PubMed and Cochrane Library database were included. Weighted mean difference, odds ratio, and surface under the cumulative ranking curve (SUCRA) values were evaluated for the efficacy and adverse events of the five targeted agents in the treatment of NSCLC. With regard to efficacy, the overall response rate (ORR) of advanced or metastatic NSCLC patients treated with gefitinib was relatively higher than those treated with placebo. Compared with patients treated with placebo, the disease control rate (DCR) of patients treated with erlotinib and with gefitinib was relatively higher. Furthermore, in terms of PFS and DCR, the SUCRA value of icotinib was the highest among the five targeted drugs. With regard to ORR, the SUCRA value of gefitinib was the highest among the five targeted drugs. In terms of fatigue, rash, and cough, erlotinib had the lowest SUCRA value, whereas vandetanib exhibited the lowest SUCRA value in terms of diarrhea. Our study suggests that the efficacies of gefitinib and icotinib for advanced or metastatic NSCLC were comparatively better, whereas the toxicities of erlotinib and vandetanib were relatively greater.

Clinical outcome of treatment of metastatic non-small cell lung cancer in patients harboring uncommon EGFR mutation.

BACKGROUND: Uncommon epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a rare subset of NSCLC. The aim of this study was to investigate the prevalence, characteristics, and clinical outcomes of metastatic NSCLC harboring uncommon EGFR mutation at Thailand's largest national tertiary hospital. The secondary objective was to compare treatment efficacy between EGFR-tyrosine kinase inhibitor (EGFR-TKI) and chemotherapy. METHODS: This retrospective chart review included patients that were tested for EGFR-mutation NSCLC during 2014-2018. Patient demographic and clinical data, treatment data, and outcome data were collected and analyzed. RESULTS: Of the 681 patients that were evaluated for EGFR mutation, 317 (47.0%) had EGFR-mutant NSCLC, and 28 (8.8%) of those harbored uncommon EGFR mutations. The median follow-up was 19.1 months. History of tobacco use was reported in 50% of patients. The most common single mutation among uncommon EGFR was exon 20 insertion (n = 6), followed by L861Q (n = 5) and G719X (n = 4). Thirteen (46%) patients had compound mutations. One hundred percent of male patients with G719X mutation were smokers. Sixteen of 28 patients were treated with EGFR-TKI. Most received first-generation EGFR-TKI, and 29% were treated with chemotherapy alone. The objective response rate was 37.5% in the EGFR-TKI group. Median progression-free survival (PFS) in the EGFR-TKI group was 10.2 months. Median PFS among the 8 patients in the chemotherapy group that received first-line platinum doublet was 6.5 months. Three-year overall survival (OS) among 28 patients was 34%. Three-year OS was significantly better in patients treated with EGFR-TKI. CONCLUSIONS: Uncommon EGFR mutations was detected in 8.8% of EGFR-mutant NSCLC. Exon 20 insertion was the most common mutation, and 50% of patients had history of tobacco use. First- or second-generation EGFR-TKI demonstrated greater OS benefit than platinum-doublet chemotherapy among patients harboring uncommon EGFR-mutant NSCLC. Survival outcomes were comparable to those reported from previous large cohort studies.

Molecular Diagnostics and Treatment Patterns in Metastatic Non-small Cell Lung Cancer Patients: Real World Evidence from Greece: LACHESIS Study.

BACKGROUND/AIM: Lung cancer, primarily non-small cell lung cancer (NSCLC), is the leading cause of cancer deaths globally. In Greece in 2020, 8,960 new cases were reported. NSCLC's 5-year survival rates range from 54% (stage I) to less than 2% (stage IV); however, innovative therapies like immune check points inhibitors (ICIs) and targeted treatments have notably enhanced outcomes. The aim of this study was to assess the 1st and 2nd line treatment patterns with the introduction of new treatment modalities. Additionally, we evaluated biomarker testing approaches in NSCLC. PATIENTS AND METHODS: LACHESIS was a retrospective multinational study, collecting and analyzing data from adult patients from Russia, Bulgaria, and Greece with metastatic NSCLC either newly diagnosed or relapsed from earlier stages, who had the option to undergo biomarker testing (genetic alterations/programmed death-ligand 1 protein expression levels, PD-L1), and who received 1st line treatment for squamous (SQ) or non-squamous (N-SQ) NSCLC. Subsequent lines of therapy were also reported. RESULTS: The Greek site registered retrospective data from 250 NSCLC patients, of whom 206 were newly diagnosed (ND) metastatic NSCLC patients and 44 were patients relapsed from earlier stages. Seventy-two had SQ NSCLC and 169 had N-SQ NSCLC. For these patients, treatment patterns including immunotherapy±chemotherapy combinations were recorded. Biomarker testing patterns, including genetic alterations and PD-L1 expression levels were also documented. CONCLUSION: LACHESIS provides treatment patterns and biomarker testing data. Greek patients were treated according to international guidelines, with immunotherapy as a viable option, particularly for PD-L1 levels over 50%. Biomarker testing, crucial for non-squamous (N-SQ) cases, should yield timely results for driver mutations, prioritizing patient benefits.

Efficacy and safety profile of combining programmed cell death-1 (PD-1) inhibitors and antiangiogenic targeting agents as subsequent therapy for advanced or metastatic non-small cell lung cancer (NSCLC).

BACKGROUND: Previous studies have demonstrated that PD-1 inhibitors are effective in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC). However, whether the combination of PD-1 inhibitors and antiangiogenic agents benefit advanced NSCLC patients as subsequent therapy remains unknown. In this study, we retrospectively reviewed the efficacy and safety profile of this combination strategy as subsequent therapy for NSCLC patients in a real-world setting. METHODS: A total of 30 patients with advanced NSCLC, who progressed after at least two cycles of platinum-based chemotherapy or targeted therapy and subsequently received combination therapy with a PD-1 inhibitor and antiangiogenic agent, were included in this study. The safety profile and efficacy were also investigated. RESULTS: At the time of a median follow-up period of 10.7 months, 28 patients had experienced progression of disease and 16 patients had died. The median progression-free survial (mPFS) was 5.0 months (95% confidence interval [CI]: 3.179-6.821), and the median overall survival (mOS) was 14.3 months (95% CI: 8.912-19.659). The objective response rate (ORR) and the disease control rate (DCR) were 10.3% and 72.4%, respectively (0 complete remission, three partial responses and 18 stable disease in 29 patients with measurable lesions). Patients with PD-L1 expression of at least 1% of tumor cells (n = 5) had relatively longer mPFS compared to those with PD-L1-negative tumors (n = 14), (11.6 months vs. 3.7 months). Treatment was suspended in two patients due to grade 3 immune-related pneumonia and pancreatitis, respectively. No novel adverse events (AEs) or grade 4 AEs were observed. CONCLUSIONS: A combination of PD-1 inhibitors and antiangiogenic targeting agents may be beneficial for patients with advanced or metastatic NSCLC as subsequent treatment, especially for patients with PD-L1 protein expression positive, and treatment is well tolerated.

The effect of PD-L1 categories-directed pembrolizumab plus chemotherapy for newly diagnosed metastatic non-small-cell lung cancer: a cost-effectiveness analysis.

BACKGROUND: The effectiveness of adding pembrolizumab to chemotherapy improve outcomes in newly diagnosed metastatic non-small-cell lung cancer (NSCLC). We aimed to evaluate the economic outcomes of first-line treatment by adding pembrolizumab to chemotherapy with and without the use of PD-L1 testing for patient selection. METHODS: A decision-analytic model was adopted to project the disease course of newly diagnosed metastatic nonsquamous and squamous NSCLC without EGFR or ALK mutations. The efficacy and toxicity data were gathered from the KEYNOTE-189 and KEYNOTE-407 trials. Transition probabilities were estimated from the reported survival probabilities in each group. Cost and health preference data were derived from published economic evaluations. The incremental cost-effectiveness ratio (ICER) was measured, and subgroup, one-way and probabilistic sensitivity analyses (PSA) were performed for exploring the model uncertainties. RESULTS: In the US context, pembrolizumab plus chemotherapy is projected to increase quality-adjusted-life year (QALY) by 1.168 and 0.988 in comparison with chemotherapy and the ICERs were $122,248 and $121,375/QALY in the whole nonsquamous and squamous patients with unconfirmed PD-L1 tumor proportion scores (TPS), respectively. After the selection of patients by PD-L1 TPS by PD-L1 testing, the ICERs of adding pembrolizumab treatment for patients with confirmed PD-L1 TPS >1% and ≥50% were $143,282 and $127,661/QALY in nonsquamous disease, and $131,495 and $121,554/QALY in squamous disease, respectively. The ICERs of adding pembrolizumab treatment for Chinese patients were higher than $40,000/QALY regardless of the histology and TPS subgroups, which highly exceed the willingness-to-pay threshold of $29,196/QALY (three times of per capita gross domestic product of China in 2018) in China. CONCLUSIONS: Pembrolizumab plus chemotherapy as first-line treatment for untreated metastatic NSCLC without EGFR or ALK mutations is a cost-effective option regardless of PD-L1 expression status in the US context, and not cost-effective in the Chinese context. However, PD-L1 categories-directed pembrolizumab could not increase the cost-effectiveness of immunotherapy.

The Role of Intratumor Heterogeneity in the Response of Metastatic Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) represent one of the most promising therapeutic approaches in metastatic non-small cell lung cancer (M-NSCLC). Unfortunately, approximately 50-75% of patients do not respond to this treatment modality. Intratumor heterogeneity (ITH) at the genetic and phenotypic level is considered as a major cause of anticancer therapy failure, including resistance to ICIs. Recent observations suggest that spatial heterogeneity in the composition and spatial organization of the tumor microenvironment plays a major role in the response of M-NSCLC patients to ICIs. In this mini review, we first present a brief overview of the use of ICIs in M-NSCLC. We then discuss the role of genetic and non-genetic ITH on the efficacy of ICIs in patients with M-NSCLC.

Durable complete response to nivolumab in a patient with HIV and metastatic non-small cell lung cancer.

Programmed death 1 (PD-1) inhibitors have been shown to increase overall survival in non-small cell lung cancer (NSCLC) patients. HIV patients have increased expression of PD-1 on their T-cell surfaces. We describe a patient with well-controlled HIV and NSCLC who underwent treatment with nivolumab and had a durable complete response (CR) with his viral load remaining undetectable. To date there is only one case report of a cancer patient with melanoma and with HIV treated with a programmed death ligand 1 (PD-L1) inhibitor. The majority of clinical trials involving PD-1 and PD-L1 inhibitors exclude HIV patients.