Chemotherapy In Advanced Non-small Cell Lung Cancer Research Articles

The relative risk of immune checkpoint inhibitor pneumonitis in advanced non-small- cell lung cancer: Meta-analyses of controlled clinical trials.

Immune checkpoint inhibitor pneumonitis (CIP) is a prevalent form of immunotherapy-induced pulmonary toxicity, ranking among the leading causes of mortality associated with immune checkpoint inhibitors (ICIs). Despite its significance, the risk stratification of CIP in advanced non-small cell lung cancer (NSCLC) remains uncertain. In this study, we conducted a comprehensive analysis, comparing various factors such as histological types, treatment regimens, PD-L1 expression levels, and EGFR/ALK negativity in advanced NSCLC. Our investigation extends to evaluating the relative risk of developing CIP based on previous treatment history. This analysis aims to provide valuable insights for the identification of specific patient subgroups at higher risk, facilitating more effective risk management and precision therapy approaches. PubMed, Embase, and Cochrane databases were systematically searched up to February 16, 2023. We conducted a screening of randomized controlled trials (RCTs) that compared ICI monotherapy or its combination with chemotherapy in advanced NSCLC. The trials were categorized based on histological type, treatment regimen, PD-L1 expression level, EGFR/ALK-negative status, and prior treatment history. Subsequently, the data were stratified into five subgroups, and the occurrences of all-grades (1-5) and high-grades (3-5) pneumonia events were extracted. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were then calculated for further analysis. Twenty-two RCTs, encompassing 13,725 patients with advanced NSCLC, were included in this analysis. Regardless of histology (OR = 2.47, 95% CI 1.41-4.33, P = 0.002; OR = 1.84, 95% CI 1.10-3.09, P = 0.02), treatment regimen (OR = 3.27, 95% CI 2.00-5.35, P < 0.00001; OR = 2.91, 95% CI 1.98-4.27, P < 0.00001), PD-L1 expression level (OR = 5.11, 95% CI 2.58-10.12, P < 0.00001; OR = 5.15, 95% CI 2.48-10.70, P < 0.0001), negative EGFR/ALK expression (OR = 4.32, 95% CI 2.22-8.41, P < 0.0001; OR = 3.6, 95% CI 1.56-8.28, P = 0.003), whether there is a history of treatment (OR = 3.27, 95% CI 2.00-5.35, P < 0.00001; OR = 2.74, 95% CI 1.75-4.29, P < 0.0001), ICI use was associated with a higher risk of all-grade (1-5) and high-grade (3-5) pneumonia compared to chemotherapy. Subgroup analysis revealed that the squamous group, the ICI vs. combination chemotherapy (CT) group, the PD-L1 > 50% group, and the previously untreated group had a higher risk of developing all-grade and grade 3-5 CIP (P < 0.05). In advanced NSCLC, ICI treatment was linked to an elevated risk of pneumonitis across all grades (1-5) as well as high-grade occurrences (3-5) compared to chemotherapy. Notably, individuals with squamous histology and high PD-L1 expression, along with those lacking a history of prior treatment, demonstrated a heightened susceptibility to developing immune-related pneumonitis of all grades (1-5) and high grades (3-5). These observations provide valuable insights for clinicians seeking to enhance the management of pulmonary toxicity associated with immunotherapy.

Clinical status and perspective on the application of immunotherapy combined with chemotherapy in advanced non-small cell lung cancer: a review.

The therapeutic landscape of advanced non-small cell lung cancer (NSCLC) has been significantly improved by developing immunotherapy represented by programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitors (ICI). Furthermore, immunotherapy combined with chemotherapy is an essential treatment strategy for driver-negative advanced NSCLC, especially in a population with PD-L1 <50%, and leads to long-term survival in the entire population regardless of the PD-L1 expression status. However, specific challenges must be overcome, including how to use immunotherapy with chemotherapy in clinics. Furthermore, the application of immunotherapy with chemotherapy in populations such as elderly patients and patients with brain metastases, oligometastases, epidermal growth factor receptor (EGFR) gene mutation, anaplastic lymphoma kinase (ALK) gene rearrangements, and other driver gene-positive populations must be further explored. The biomarkers associated with immunotherapy and chemotherapy are still unclear, and the search for predictive biomarkers can contribute toward more precise and personalized immunotherapy. Furthermore, treatment strategies after immunotherapy and chemotherapy resistance are of significant focus clinically, and clinical studies with multiple combination therapy strategies are ongoing. Therefore, based on the reported status of immunotherapy combined with chemotherapy for advanced NSCLC, this study conducted a comprehensive literature review by searching keywords "PD-1 and PD-L1, immune checkpoint inhibitor (ICI), and NSCLC" in MEDLINE, major conferences, and major clinical research projects to elucidate the therapeutic efficacy of immunotherapy combined with chemotherapy as the current first-line treatment approach for various types of NSCLC patients. Additionally, it addresses several pressing challenges associated with immunotherapy combined with chemotherapy, including enhancing treatment response and survival rate in specific patient populations and identifying potential biomarkers.

Economic evaluation of toripalimab combined with chemotherapy in the treatment of non-small cell lung cancer.

The CHOICE-01 trial showed that toripalimab plus chemotherapy achieved satisfactory outcomes compared with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who were negative for driver genes, but the economics of this regimen is unclear. Therefore, this study aimed to evaluate the cost-effectiveness of toripalimab in combination with chemotherapy in advanced NSCLC with negative driver genes from the perspective of the Chinese healthcare system. A three-state partitioned survival model was developed to simulate the costs and outcomes associated with adding toripalimab to first-line chemotherapy. The clinical data in the model came from the CHOICE-01 trial, only direct medical costs were included, and utility values were referred to the literature. Four models were applied to explore the differences in the results of fitting and extrapolating K-M curves from different models, and cost-effectiveness subgroup analysis was performed. The incremental cost-effectiveness ratio (ICER) was used as the main outcome measure. Sensitivity analysis was performed to assess the impact of parameter uncertainty on the model. The baseline analysis showed that toripalimab coupled with chemotherapy cost $21,052 more than chemotherapy ($43,197 vs. $22,145) and also gained 0.71 QALYs more (1.75 QALYs vs. 1.03 QALYs), with an ICER of $29,478/QALYs. At the current willingness-to-pay threshold ($35,108/QALY), the extra cost was well worth it. The results of fitting and extrapolating the survival curves using other models were consistent with the results of the standard parametric model. Subgroup analysis demonstrated that the addition of toripalimab to chemotherapy was economical. Sensitivity analysis showed that the utility values of PD and PFS stages had the greatest impact on the model. From the viewpoint of the Chinese healthcare system, toripalimab combined with chemotherapy in the treatment of advanced NSCLC with negative driver genes was likely to be cost-effective compared with chemotherapy.

The Comparison of Toxicities between Paclitaxel-Carboplatin Regimen versus Gemcitabine-Carboplatin Regimen as Palliative Chemotherapy for Advanced Non-Small Cell Lung Cancer

Introduction: Advanced Non-Small Cell Lung Cancer (NSCLC) is a serious condition characterized by the spread of cancer beyond the lungs, commonly adenocarcinoma and squamous cell carcinoma. Palliative chemotherapy is used to manage advanced NSCLC, focusing on relieving symptoms and improving quality of life rather than curing the disease. Paclitaxel-Carboplatin and Gemcitabine-Carboplatin are commonly used regimens for palliative chemotherapy in advanced NSCLC. Comparing the toxicities of these two regimens is important to determine which one has fewer side effects for patients. Aim of the Study: The aim of the study was to compare the toxicities of Paclitaxel-Carboplatin and Gemcitabine -Carboplatin as palliative chemotherapy for Advanced Non-Small Cell Lung Cancer. Methods: This Quasi- Experimental study was conducted at the Department of Medical Oncology, Combined Military Hospital, Dhaka, Bangladesh, the National Institute of Cancer Research &amp; Hospital (NICRH), Mohakhali, Dhaka, Bangladesh, and the Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbagh, Dhaka, Bangladesh. The study duration was 10 months, from January 2022 to October 2022. During this period, a total of 74 participants were divided into two equal groups, Arm-A receiving the Paclitaxel-Carboplatin treatment regimen, and Arm-B receiving the Gemcitabine- Carboplatin treatment regimen. Result: The majority of participants in both Arm-A and Arm-B were in the age group of 51-60 years (40.54% in Arm-A, 43.24% in Arm-B) with an overall mean age of 58.35 years in Arm-A and 57.54 years in Arm-B. An overall male prevalence was observed, with 78.38% of participants in Arm-A and 70.27% in Arm-B being male. The majority of participants had an ECOG status of 1 (45.95% in Arm-A, 59.46% in Arm-B). Risk factors such as smoking and various lung diseases were present among participants, but there was no significant difference between the two arms. After 6 weeks of follow-up, 62.16% of Arm-A and 56.76% of ...

Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients.

Circulating tumor cells (CTCs) are prognostic biomarker in non-small-cell lung cancer (NSCLC). CTCs could also be used as predictor of efficacy of systemic treatments in advanced NSCLC. We described the dynamic changes of CTCs during first-line platinum-based chemotherapy in advanced NSCLC and clarified the correlation between CTC counts and efficacy of chemotherapy. Chemotherapy is administered and blood specimens are collected at four time points from baseline to disease progression for CTC detection. This multicenter prospective study enrolled patients with previously untreated stage III or IV NSCLC fit for standard platinum-based chemotherapy. Bloods were sampled as per standard operating procedures at baseline, cycle 1 and cycle 4 of chemotherapy, and at disease progression for CTC analysis using the CellSearch system. Among 150 patients enrolled, median overall survival (OS) was 13.8, 8.4, and 7.9 months in patients with CTC-, KIT-CTC, and KIT+CTC at baseline (p = 0.002). Patients with persistent negative CTC (46.0%) had longer progression-free survival [5.7 months, 95% confidence interval (CI): 5.0-6.5 versus 3.0 months, 0.6-5.4; hazard ratio (HR): 0.34, 95% CI: 0.18-0.67) and OS (13.1 months, 10.9-15.3 versus 5.6 months, 4.1-7.1; HR: 0.17, 0.08-0.36) compared with patients with persistent positive CTC (10.7%), which was not impacted by chemotherapy. Chemotherapy decreased CTC from 36.0% (54/150) to 13.7% (13/95). CTC persistent presence during treatment represents poor prognosis and resistance to chemotherapy in advanced NSCLC. Chemotherapy could effectively eliminate CTCs. Molecular characterization and the functionalization of CTC will be warranted for further intensive investigation. NCT01740804.

Cost-effectiveness of nivolumab plus ipilimumab versus chemotherapy as first-line therapy in advanced non-small cell lung cancer.

First-line treatment with nivolumab plus ipilimumab has been shown to improve overall survival (OS) and progression-free survival (PFS) for patients with advanced non-small cell lung cancer (NSCLC). The current study evaluated the cost-effectiveness of nivolumab plus ipilimumab versus chemotherapy in advanced NSCLC from the perspective of Chinese healthcare system. A three state-transition Markov model was employed to evaluate the cost and effectiveness of nivolumab plus ipilimumab versus chemotherapy in the first-line treatment of advanced NSCLC. Key clinical data in the model were derived from Part 1 of the phase 3 CheckMate 227 trial (NCT02477826). Costs and utilities were obtained from published literatures. The main endpoints of the model were costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to assess the model uncertainty. Nivolumab plus ipilimumab was associated with an increase in overall cost of $95,867.82 and improved effectiveness of 0.98 QALYs compared with chemotherapy, yielding an ICER of $97,676.24 per QALY. In one-way sensitivity analysis, the variables that had the greatest influence on the ICER were hazard ratio for OS and body weight. In probabilistic analysis, nivolumab plus ipilimumab had a 0% probability of being cost-effective at a willingness-to-pay (WTP) threshold of $37,663.26/QALY in China. However, the combination therapy would become cost-effective when the cost of nivolumab and ipilimumab were discounted by 65%. First-line nivolumab plus ipilimumab treatment for advanced NSCLC was found to be not cost-effective compared with chemotherapy at a WTP threshold of $37,663.26/QALY in China.

An exploration of LAF-bTMB as a predictor for the efficacy of immunotherapy combined with chemotherapy in non-small cell lung cancer.

Immune checkpoint inhibitor (ICI) combined with chemotherapy is one of the standards of care for advanced non-small cell lung cancer (NSCLC) without driver mutations. However, the biomarker of combination therapy is still unknown. Although previous studies have confirmed that low allele frequency adjusted blood-based tumor mutational burden (LAF-bTMB) is associated with the efficacy of ICI monotherapy, there has been no report on the correlation between the efficacy of LAF-bTMB and ICI combined chemotherapy. This study aimed to explore whether LAF-bTMB can be used as a predictive biomarker for the efficacy of immunotherapy combined with chemotherapy in advanced NSCLC. This study enrolled patients diagnosed with advanced NSCLC and who received ICI combined with chemotherapy for first-line therapy from May 2020 to December 2021 at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Clinical information, treatment information, survival data, and peripheral blood samples of every patient before treatment were collected. Next-generation sequencing was performed on plasma samples to estimate bTMB and LAF-bTMB. A total of 42 patients with NSCLC were enrolled. In this cohort, 19 patients achieved partial response (PR), and the objective response rate (ORR) was 45.2%. The median progression-free survival (PFS) of all patients was 13.4months (95% CI, 7.49-19.72). Both PFS and the overall survival (OS) were significantly longer in the responder (R) group than in the non-responder (NR) group (median PFS, 16.4months vs. 7.2months, p= 0.028; median OS, NE vs. 9.3months, p= 0.016). There was no significant difference in bTMB and LAF-BTMB between the R and NR group. The ORR of patients with LAF-bTMB≤8muts/Mb was significantly higher than that of patients with LAF-bTMB >8muts/Mb (ORR, 61% vs. 26%, respectively, p= 0.033). When LAF-bTMB ≤8muts/Mb or > 20muts/Mb, ORR was significantly higher than that of patients with LAF-bTMB between 8 and 20muts/Mb (ORR were 57% and 21%, p= 0.047). No correlation has been found between LAF-bTMB and PFS or OS. This study confirmed that neither bTMB nor LAF-bTMB is feasible as a potential predictor of first-line immunochemotherapy for advanced NSCLC. More suitable biomarkers need to be explored to screen patients with better efficacy of immunotherapy combined with chemotherapy in the future.

Trajectory of health-related quality of life during the last year of life in patients with advanced non-small–cell lung cancer

BackgroundThe aims of this study were to assess the trajectory of health-related quality of life (HRQOL) during the last year of life in patients with advanced non-small–cell lung cancer (NSCLC) and to explore when and to what degree deterioration of symptoms and physical functioning accelerate towards the end of life.MethodsData from two RCTs of first-line chemotherapy in advanced NSCLC was analyzed. HRQOL was assessed repeatedly using the EORTC QLQ-C30 and LC13. Changes in HRQOL scores were investigated relative to the time of death.ResultsThe study sample included 730 patients, with a median of four HRQOL assessments per patient (range 1–9). Fatigue, dyspnea, appetite loss, and cough were the most pronounced symptoms in all phases of the disease trajectory. The deterioration rates of global quality of life, physical function, and key symptoms were relatively slow until 4 months before death. Then, the decline accelerated, and for physical function, fatigue, and dyspnea, there was a very rapid decline in the last 2 months.ConclusionsPatients with advanced NSCLC experience a high symptom burden that worsens over time, especially in the last 4 months. Regular symptom monitoring may help identify where patients are in the disease trajectory, serve as a trigger for changes in anticancer and symptomatic treatment, and facilitate discussions about end-of-life care.

P1.15-12 Patient-reported Outcomes of Cemiplimab versus Chemotherapy in Advanced NSCLC: PD-L1 Level Subgroups in EMPOWER-Lung 1

Previously reported subgroup analysis of EMPOWER-Lung 1 (NCT03088540), a randomised 1:1 open-label Phase 3 study, showed incremental improvements in overall survival and progression-free survival with cemiplimab monotherapy (CEMI, n=283) versus platinum-doublet chemotherapy (CHEMO, n=280) as programmed cell death-ligand 1 (PD-L1) expression increased from ≥50% to ≥90% (overall survival with PD-L1 ≥50% to ≤60%: hazard ratio [HR] 0.77, 95% confidence interval [CI, 0.49, 1.23]; with PD-L1 >60% to <90%: HR 0.47, 95% CI [0.27, 0.80]; with PD-L1 ≥90%: HR 0.46, 95% CI [0.25, 0.85]) in patients with advanced non-small cell lung cancer (NSCLC) with PD-L1 ≥50%.

Anti-Angiogenic Therapy in ALK Rearranged Non-Small Cell Lung Cancer (NSCLC).

The management of advanced lung cancer has been transformed with the identification of targetable oncogenic driver alterations. This includes anaplastic lymphoma kinase (ALK) gene rearrangements. ALK tyrosine kinase inhibitors (TKI) are established first-line treatment options in advanced ALK rearranged non-small cell lung cancer (NSCLC), with several next-generation ALK TKIs (alectinib, brigatinib, ensartinib and lorlatinib) demonstrating survival benefit compared with the first-generation ALK TKI crizotinib. Still, despite high objective response rates and durable progression-free survival, drug resistance inevitably ensues, and treatment options beyond ALK TKI are predominantly limited to cytotoxic chemotherapy. Anti-angiogenic therapy targeting the vascular endothelial growth factor (VEGF) signaling pathway has shown efficacy in combination with platinum-doublet chemotherapy in advanced NSCLC without a driver alteration, and with EGFR TKI in advanced EGFR mutated NSCLC. The role for anti-angiogenic therapy in ALK rearranged NSCLC, however, remains to be elucidated. This review will discuss the pre-clinical rationale, clinical trial evidence to date, and future directions to evaluate anti-angiogenic therapy in ALK rearranged NSCLC.

Choline Kinase α Inhibitors MN58b and RSM932A Enhances the Antitumor Response to Cisplatin in Lung Tumor Cells

Lung cancer is one of the main causes of death in developed countries, and non-small cell lung cancer (NSCLC) is the most frequent type (80% of patients). In advanced NSCLC, platinum-based chemotherapy is the frontline palliative treatment, but less than 5% of patients achieve prolonged survival. Immunotherapy has recently been proposed as the standard of care (SoC) as either monotherapy or in combination with chemotherapy for advanced NSCLC. The levels of expression of PD-L1 are the only predictive biomarkers for patient assessment. Although around 30% of patients receiving immunotherapy achieve 5-year survival, a significant number does not benefit from this novel therapeutic approach. Therefore, there is a need for novel strategies to improve clinical outcomes. The expression level of choline kinase α (ChoKα) is increased in a large number of human tumors, including NSCLC tumors, and constitutes an independent prognostic factor for early-stage NSCLC patients. Thus, ChoKα has been postulated as a new target drug in cancer therapy. The combination of cisplatin with novel targeted drugs such as choline kinase inhibitors may improve both the survival rates and the quality of life of NSCLC patients and may serve as the basis for the development of new therapeutic approaches. To that aim, we developed several in vitro and in vivo approaches to assess the antitumor activity of a novel combination regimen using cisplatin and ChoKα inhibitors. Our results suggest that a proper combination of specific inhibitors of the NSCLC prognostic factor ChoKα and platinum-based conventional chemotherapy might constitute a new, efficient treatment approach for NSCLC patients. This novel approach may help reduce the toxicity profile associated with cisplatin since, despite the advances in NSCLC management in recent years, the overall 5-year survival rate is still poor.

Immune checkpoint inhibitors for first-line treatment of advanced non-small-cell lung cancer: A systematic review and network meta-analysis.

ObjectiveCurrently, several immune checkpoint inhibitors (ICIs) treatment for advanced non‐small‐cell lung cancer (NSCLC) have been investigated; their overall efficacy and safety remain unclear.MethodsWe searched electronic databases such as PubMed, EMBASE, and the Cochrane library. The randomized controlled trials (RCTs) that compared ICIs with or without chemotherapy to chemotherapy in advanced NSCLC. We collected and compaired thier parameters, including overall survival (OS), progression‐free survival (PFS), objective response rate (ORR), and treatment‐related adverse events (TRAEs) of grade ≥3.ResultsA total of 15 RCTs involving 8869 patients with NSCLC were included. Pembrolizumab plus platinum‐based chemotherapy had higher OS and PFS than platinum‐based chemotherapy (hazard ratio [HR] 0.55, 95% CI 0.46–0.67; HR 0.54, 95% CI 0.41–0.70, respectively). Pembrolizumab plus platinum‐based chemotherapy had higher ranked ORR than platinum‐based chemotherapy (odds ratio [OR] 2.92, 95% CI 1.99–4.22). In terms of OS, atezolizumab, pembrolizumab plus platinum‐based chemotherapy, and nivolumab plus ipilimumab ranked as the best treatments for patients with programmed death‐ligand 1 (PD‐L1) expression levels of ≥50%, 1–49%, and <1%, respectively. In terms of PFS, pembrolizumab plus platinum‐based chemotherapy ranked as the best treatment for patients with any PD‐L1 expression levels. However, ipilimumab plus platinum‐based chemotherapy, nivolumab plus platinum‐based chemotherapy, and atezolizumab plus platinum‐based chemotherapy have higher TRAEs of grade ≥3 than platinum‐based chemotherapy.ConclusionsPembrolizumab plus platinum‐based chemotherapy prevailed in rank in OS, PFS, and ORR benefit. The TRAEs of pembrolizumab plus platinum‐based chemotherapy were more than ICI monotherapy and chemotherapy.

1332P A randomized phase II trial of standard versus low-dose nab-paclitaxel for previously treated advanced non-small cell lung cancer (JMTO LC14-01)

Nanoparticle albumin-bound (nab) paclitaxel is an active agent for non–small cell lung cancer (NSCLC). Nab-paclitaxel proved to be noninferior to docetaxel with regard to overall survival (OS), having showcased improved progression-free survival (PFS) and overall response rate (ORR) in patients with previously treated advanced NSCLC, according to findings from the phase III trial in Japan (J-AXEL study, 2021). In chemotherapy for advanced NSCLC, it is expected that administration of the optimal dose for as long as possible will lead to improvement of prognosis rather than administration of the maximum tolerated dose for a short period of time.

Pembrolizumab Alone or Combined With Chemotherapy in Advanced NSCLC With PD-L1 ≥50%: Results of a Retrospective Study.

ObjectivesPembrolizumab plus platinum-based chemotherapy and pembrolizumab monotherapy (PM) both become standard of care in patients with advanced non-small-cell lung cancer (NSCLC) and a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) greater than 50%. This study aimed to figure out the better treatment choice.MethodIn this retrospective analysis, we compared the clinical efficacy of PM and PC as first-line treatment in NSCLC patients with a PD-L1 ≥50% and negative for genomic alterations in the EGFR and ALK genes.ResultAmong the population, 115 patients received PC, and 91 patients received PM. Up to Dec 30, 2020, median follow-up was 17.13 months. The median progression-free survival (PFS) rates of PC and PM were 12.37 and 9.60 months (HR: 0.44, p < 0.001), respectively. The median overall survival (OS) rates were NE and 28.91 months (HR: 0.40, p = 0.005), respectively. Subgroup analysis found that the PFS benefit of PC was evident in most subgroups excepting patients with brain metastasis. The 1-year overall survival rates of PC and PM were 89.3% and 76.1%, respectively. The ORR was 61.7 and 46.9% (p = 0.004), respectively.ConclusionIn patients with previously untreated, PD-L1 ≥50%, advanced NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard platinum-based chemotherapy seems to be the preferred treatment, which needs to be validated by further prospective trials.

Correlation between MTHFR 677C &gt; T polymorphism and response of pemetrexed-based chemotherapy in advanced NSCLC: A meta-analysis

Abstract Objective The aim of this study was to investigate the correlation between MTHFR 677C &gt; T polymorphism and response of pemetrexed-based chemotherapy in advanced non-small-cell lung cancer (NSCLC) by pooling the open published relevant studies. Methods Clinical studies associated with MTHFR 677C &gt; T polymorphism and response of pemetrexed-based chemotherapy in advanced NSCLC were systematically searched in databases of Pubmed, Embase, Cochrance Library, China national knowledge infrastructure (CNKI) and Wanfang. The correlation was expressed by odds ratio (OR) and corresponding 95% confidence interval (95% CI). The publication bias of the included studies was evaluated through Begg’s funnel plot and Egger’s line regression test. Results Ten prospective clinical studies relevant to MTHFR 677C &gt; T polymorphism and response of pemetrexed-based chemotherapy in NSCLC were included in the present meta-analysis. The pooled results indicated that the partial response in NSCLC patients with TT or CT genotype was inferior to CC genotype in a dominant gene model (TT + CT vs CC) (OR = 0.16, 95% CI: 0.06–0.41, P = 0.001). NSCLC cases with T genotype were inferior to C genotype in the objective response rate treated with pemetrexed-based chemotherapy for dominant (OR = 0.28, 95% CI: 0.18–0.45, P = 0.001), recessive (OR = 0.43, 95% CI: 0.19–0.94, P = 0.03) and homozygous models (OR = 0.30, 95% CI: 0.13–0.67, P = 0.003). However, there was no statistical difference in disease control rate, progressive disease between different genotypes of different gene models (P all &gt; 0.05). Conclusion The pemetrexed-based chemotherapy response was decreased in NSCLC cases with T genotype, which can be applied as a potential pemetrexed-based chemotherapy response marker.

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer.

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer.

IMpower132: Atezolizumab plus platinum‐based chemotherapy vs chemotherapy for advanced NSCLC in Japanese patients

IMpower132 explored the safety and efficacy of atezolizumab plus pemetrexed and platinum‐based chemotherapy as first‐line treatment for advanced non‐small‐cell lung cancer (NSCLC). Key eligibility criteria for the phase 3, open‐label, IMpower132 study included age ≥18 y, histologically or cytologically confirmed advanced non‐squamous NSCLC per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status of 0/1, and no prior systemic treatment for stage IV NSCLC. Patients received atezolizumab (1200 mg) plus pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) or carboplatin (area under the concentration curve, 6 mg/mL/min) (APP arm) or chemotherapy alone (PP arm). The co‐primary study endpoints were overall survival (OS) and investigator‐assessed progression‐free survival (PFS) per RECIST 1.1 in the intention‐to‐treat population. A subgroup analysis was conducted in Japanese patients. In the Japanese subgroup (n = 101), median OS was 30.8 (95% CI, 24.3 to not estimable) mo in the APP arm (n = 48) and 22.2 (95% CI, 15.7‐30.8) mo in the PP arm (n = 53; hazard ratio [HR], 0.63 [95% CI, 0.36‐1.14]). PFS was 12.8 (95% CI, 8.6‐16.6) mo in the APP arm vs 4.5 (95% CI, 4.1‐6.7) mo in the PP arm (HR, 0.33 [95% CI, 0.21‐0.58]). Grade 3/4 treatment‐related adverse events (TRAEs) occurred in 68.8% of APP arm patients and 44.2% of PP arm patients. Consistent with global study results, atezolizumab plus pemetrexed and platinum‐based chemotherapy improved efficacy and was well tolerated in Japanese patients with advanced NSCLC despite a higher incidence of grade 3/4 TRAEs.

A phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected non-small-cell lung cancer with EGFR mutation (West Japan Oncology Group 11719L/ADJUST study)

Background:Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is a standard treatment in EGFR-mutated advanced non-small-cell lung cancer (NSCLC); however, previous data have suggested that EGFR-TKI has limited potential as adjuvant therapy. On the contrary, based on subset analysis with the immune checkpoint inhibitor (ICI) plus platinum-doublet chemotherapy in advanced NSCLC with EGFR mutation, we hypothesized that this combination was worth testing as adjuvant therapy in patients with EGFR-mutated NSCLC.Methods:Herein, we introduce our phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected NSCLC with EGFR mutation. Accrued patients will be pathological stage II–IIIA with completely resected NSCLC and whose tumors have EGFR mutation. Treatment comprises four cycles of cisplatin plus vinorelbine combined with atezolizumab followed by maintenance with atezolizumab. The primary endpoint is the disease-free survival (DFS) rate at 2 years. Secondary endpoints are DFS, overall survival, and safety. In total, 18 patients will be enrolled in this study.Discussion:Ongoing phase III trials of adjuvant ICI allow the inclusion of patients with EGFR mutation, but our current trial will provide the earliest clinical data on the efficacy of platinum-doublet chemotherapy with atezolizumab.

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer.

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer.

Plasma Heat Shock Protein 90 Alpha: A Valuable Predictor of Early Chemotherapy Effectiveness in Advanced Non-Small-Cell Lung Cancer.

BackgroundHeat shock protein-90 alpha (HSP90α) is more abundant in non-small-cell lung cancer (NSCLC) patients than in control individuals. However, whether it can reflect chemotherapy efficacy remains unknown. This study aimed to investigate the association of HSP90α with chemotherapy in advanced NSCLC.Material/MethodsWe retrospectively evaluated data from patients admitted to the Department of Respiratory Medicine, Shaoxing People’s Hospital, from September 2016 to September 2018 with stage IIIB or IV NSCLC and administered 4 cycles of third-generation platinum-based combination chemotherapy (2 drugs simultaneously). Based on the RECIST1.1 criteria, complete remission (CR), partial response (PR), and stable disease (SD) in 60 cases were determined before and after chemotherapy. Before chemotherapy and after 1, 2, and 4 cycles of chemotherapy, plasma HSP90α levels were quantitated by ELISA. Chest CT was performed before and after 2 and 4 cycles of chemotherapy.ResultsAfter 1–4 cycles of chemotherapy, plasma HSP90α levels were significantly lower than pre-chemotherapy levels (P<0.05). The sums of the longest tumor diameters after 2 and 4 cycles of chemotherapy were decreased compared with pre-chemotherapy values (P<0.05). Plasma HSP90α levels and tumor size showed no significant correlation before and after chemotherapy (r=0.244, P=0.06).ConclusionsPlasma HSP90α can be considered a valuable predictor of early chemotherapy effectiveness in advanced NSCLC, and is positively correlated with tumor remission after chemotherapy. However, plasma HSP90α level is not correlated with tumor diameter and pathological type.