Cell Lung Cancer In Japan Research Articles

Patient-Initiated Nationwide Survey on Testing for Actionable Oncogenic Drivers in Non-Small Cell Lung Cancer in Japan.

Previous reports indicated still low implementation rates of multigene testing for advanced non-small cell lung cancer (NSCLC) in Japan. This is a retrospective study launched at the initiative of lung cancer patients. Patients with stage IV NSCLC from January 2019 to December 2022 were investigated for testing of 8 actionable oncogenic drivers with targeted therapies available as of 2022. A total of 15,719 patients were included. Between 2019 and 2022, the percentage of patients who were not tested for any actionable oncogenic drivers remained the same, ranging from 21.5% to 33.1%. However, since late 2021, the percentage of patients tested for five or more actionable oncogenic drivers has increased. Across hospital categories and regions, the number of actionable oncogenic drivers tested was similar. This patient-initiated national survey in Japan reveals the recent nationwide increase in testing rates for actionable oncogenic drivers in Advanced NSCLC.

Impact of First-Line Osimertinib and Other EGFR-Tyrosine Kinase Inhibitors on Overall Survival in Untreated Advanced EGFR-Mutated Non-small Cell Lung Cancer in Japan: Updated Data from TREAD Project 01.

Osimertinib shows higher effectiveness than first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in the initial treatment of EGFR-mutated non-small cell lung cancer. However, its superiority in terms of overall survival in the Asian population, especially Japanese patients, remains uncertain. To evaluate the survival benefit ofosimertinib over other EGFR-TKIs in Japanese patients, using real-world data. METHODS: As part of the Tokushukai REAl-world Data project, a retrospective multi-institutional study across 46 hospitals in Japan was conducted to evaluate the overall survival of patients with advanced EGFR-mutated non-small cell lung cancer using propensity score matching. The study involved patients receiving osimertinib as the first-line treatment (1L-Osi), those initially treated with other EGFR-TKIs (1L-non-Osi), and those receiving osimertinib after initial EGFR-TKI treatment (2L/later-Osi) between April 2010 and December 2022 and followed up until April 2023. Among 1062 Japanese patients with EGFR-mutated non-small cell lung cancer, 416 (39.2%) received 1L-Osi, while 646 (60.8%) received 1L-non-Osi, including 139 (13.1%) who received 2L/later-Osi. Within these groups, 416 (39.2%), 293 (27.6%), and 75 (7.1%) patients received first-line EGFR-TKI treatment post-osimertinib approval as a later-line treatment in Japan (March 2016). After propensity score matching, the overall survival of the 1L-Osi group was comparable to that of the 1L-non-Osi group in the post-March 2016 subset (n = 283, 42.0 vs 42.4 months). Similar trends were observed in the Del19 and L858R subgroups. The median overall survival of the 2L/later-Osi group was notably long: 60.2 months post-March 2016 (n = 75). A subgroup analysis based on initial EGFR-TKI treatment in the 1L-non-Osi and 2L/later-Osi groups revealed no significant differences among the gefitinib, erlotinib, and afatinib groups. Based on real-world data, osimertinib did not show a significant improvement in overall survival compared to other EGFR-TKIs as a first-line treatment for EGFR-mutated advanced non-small cell lung cancer in the Japanese (Asian) population. This study was registered at the University Hospital Medical Information Network Clinical Trials Registry on 9 March, 2023 (identification UMIN000050552).

Cost-effectiveness of multigene sequencing test and treatment for metastatic non-small cell lung cancer: A unique setting in the initial adoption phase in Japan allowing testing only after standard treatment

ObjectiveTo clarify the cost-effectiveness of comprehensive diagnosis and treatment of metastatic non-small cell lung cancer in Japan, from initial diagnosis to post-standard treatment, using three different strategies. MethodsA decision tree was created using three diagnostic and treatment strategies, assuming that Foundation One CDx (F1CDx), a comprehensive genome panel, was introduced in Japan in June 2019. This comprehensive decision tree includes Markov models, cost-effectiveness analyses (CEA), and cost-utility analyses (CUA) of the three strategies from the perspective of Japanese payers. Specifically, Strategy1 involves single-gene testing at the initial diagnosis and F1CDx after standard treatment; Strategy2 involves only single-gene testing at the initial diagnosis; Strategy3 involves F1CDx at the initial diagnosis. The incremental cost-effectiveness ratios (ICERs) of the three strategies are estimated. Sensitivity analyses were performed to assess the uncertainty of the parameter settings. ResultsStrategy3 was dominated for both CUA and CEA. The ICER/quality-adjusted life year (QALY) for Strategy2 versus Strategy1 was USD 13,734 (JPY 2,080,923, USD 1 = JPY 151.39 on April 1st, 2024), which is less than the willingness to pay of USD 45,900 (JPY 7,500,000), and Strategy2 was more cost-effective than Strategy1. F1CDx was not cost-effective compared to multiple simultaneous single tests at the initial diagnosis, either after standard treatment or at the initial diagnosis. Sensitivity analysis also showed that the most influential factor on the ICER for both CEA and CUA was treatment cost. ConclusionsFrom both patient benefit and health economic perspectives, introducing F1CDx after standard treatment in June 2019 was not as cost-effective as multiple simultaneous single tests at the initial diagnosis but was more realistic from a health economic perspective than introducing F1CDx at the time of initial diagnosis. Therefore, the policy at the time of F1CDx introduction in Japan was appropriate from a short-term health-economic perspective.

Cost-Utility Analysis of Stereotactic Body Radiation Therapy Versus Surgery for Patients With Stage I Non-small Cell Lung Cancer in Japan.

Stereotactic body radiation therapy (SBRT) for patients with operable stage I non-small cell lung cancer (NSCLC) is less invasive than surgery. However, differences in lifetime costs and patient outcomes remain unclear. In this study, a cost-utility analysis of SBRT compared with surgery for Japanese patients with operable stage I NSCLC was conducted. A partitioned survival model was constructed using each treatment arm's overall survival (OS) and progression-free survival (PFS) data. The data for the SBRT arm were extracted from the Japanese multicenter cohort study, which enrolled 678 medically operable patients with stage I NSCLC, and patient registry data were used for the surgery arm. The 5-year OS rate was 78.2% for SBRT and 74.8% for surgery from both studies. The 5-year PFS rate was 57.0% for SBRT and 63.4% for surgery. The quality of life values of PFS and progressive disease were obtained from domestic and overseas literature (PFS: 0.74, progressive disease: 0.65). The time horizon was set to 10 years. The expected costs and quality-adjusted life years for each treatment group were calculated. All costs are expressed in Japanese yen converted to US dollars (USD). SBRT was the dominant strategy, reducing treatment costs by 4,443.8 USD and increasing quality-adjusted life years by 0.131 compared with surgery. According to probabilistic sensitivity analysis, the probability of SBRT being dominant and cost-effective was 50.6% and 72.4%, respectively. Under the budget impact analysis, the total savings for the patients with stage I NSCLC in Japan was 6,252,870.0 USD (n = 1,407). SBRT is a more cost-effective option than surgery in patients with medically operable stage I NSCLC in Japan. Large-scale epidemiologic studies that reflect the latest clinical realities, such as OS/PFS, will be needed to validate this study's robustness.

EE504 Cost-Effectiveness Analysis of Tremelimumab As First-Line Therapy for Metastatic Non-Small Cell Lung Cancer in Japan

EE504 Cost-Effectiveness Analysis of Tremelimumab As First-Line Therapy for Metastatic Non-Small Cell Lung Cancer in Japan

EE380 Cost-Effectiveness Analysis of Erlotinib Plus Bevacizumab As First-Line Therapy for Advanced EGFR Mutation-Positive Non-Squamous Non-Small Cell Lung Cancer in Japan

Although erlotinib plus bevacizumab significantly prolonged progression-free survival compared to erlotinib monotherapy in Japanese patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), its cost-effectiveness is not necessarily clear. This study aimed to evaluate the cost-effectiveness of erlotinib plus bevacizumab compared with erlotinib alone in Japanese patients with EGFR positive NSCLC.

Health Care Resource Use Among Patients with Advanced Non–Small Cell Lung Cancer in Japan, 2017–2019

First-line immune checkpoint inhibitor (ICI) monotherapy for advanced non-small cell lung cancer (NSCLC) was introduced in Japan in February 2017. Limited information is available since that time regarding health care resource use for NSCLC in Japan, where the hospitalization burden is high. We evaluated health care resource use from first- through third-line systemic anticancer therapy for patients with advanced NSCLC included in a multicenter, retrospective chart review study. Eligible patients were aged 20 years or older with unresectable locally advanced/metastatic NSCLC with no known actionable genomic alteration who initiated first-line systemic anticancer therapy from July 1, 2017, to December 20, 2018, at 23 Japanese hospitals. We calculated the percentage of patients with a record of each resource used, the total number of each resource, and the resource use per 100 patient-weeks of follow-up from initiation of first-, second-, and third-line therapy, overall and by the 3 most common regimen categories, namely, ICI monotherapy, platinum-doublet chemotherapy (without concomitant ICI), and nonplatinum cytotoxic regimens (nonplatinum). Study follow-up ended September 30, 2019. Among 1208 patients (median age = 70 years; 975 [81%] men), 463 patients (38%) received ICI monotherapy, 647 (54%) received platinum-doublet chemotherapy, and 98 (8%) received nonplatinum regimens as first-line therapy. During the study, 621 (51%) patients initiated second-line, and 281 (23%) initiated third-line therapy. The majority of patients experienced ≥1 hospitalization (76%-94%) and ≥1 outpatient visit (85%-90%) during each therapy line. The number of hospitalizations increased from 6.5 per 100 patient-weeks in first-line to 8.0 per 100 patient-weeks in third-line. During first-line therapy, the number of hospitalizations per 100 patient-weeks were 4.8, 8.4, and 6.5 for patients receiving ICI monotherapy, platinum-doublet chemotherapy, and nonplatinum regimens, respectively, and the percentages of hospitalizations categorized as attributable to NSCLC treatment administration (no surgery, procedure, treatment of metastasis, or palliative lung radiation) were 64%, 77%, and 73%, respectively. The number of outpatient visits increased from 43.0 per 100 patient-weeks in first-line to 51.4 per 100 patient-weeks in third-line therapy. During first-line therapy, outpatient visits per 100 patient-weeks were 41.0, 46.7, and 33.0 for patients receiving ICI monotherapy, platinum-doublet chemotherapy, and nonplatinum regimens, respectively, and the percentages of outpatient visits for infusion therapy were 48%, 34%, and 36%, respectively. The results of this study, although solely descriptive, showed differing patterns of health care resource use during first-line therapy among the 3 common systemic anticancer therapy regimens for advanced NSCLC in Japan and suggest that further research is needed to investigate these apparent differences by treatment regimen.

Changes in survival of patients with non-small cell lung cancer in Japan: An interrupted time series study.

The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) gefitinib and erlotinib were approved for metastatic or relapsed non-small cell lung cancer (NSCLC) in Japan in 2002 and 2007, respectively. EGFR mutation testing was also approved in 2007. Although clinical trials showed efficacy in NSCLC patients harboring activating EGFR mutations, these effects have rarely been reported in real-world practice. We evaluated changes in survival in NSCLC patients following introduction of these agents and EGFR mutation testing by extracting patients diagnosed with NSCLC from 1993 through 2011 from six prefectural population-based cancer registries in Japan. Relative survival (RS) was calculated by sex, histological subtype, and cancer stage. We conducted interrupted time series analysis to assess survival changes following introduction of EGFR-TKIs and EGFR mutation testing. 120,068 patients with NSCLC were analyzed. One- and three-year RS gradually increased in overall NSCLC for men and women. For adenocarcinoma, among men, slopes of 1- and 3-year RS increased steeply in patients diagnosed from 2007 through 2011; among women, significant level increases were seen in 1-year RS in patients diagnosed in 2002 (4.55% [95% confidence interval: 1.76-7.33]) and 2007 (3.40% [1.27-5.52]). These significant level increases were particularly obvious in women with adenocarcinoma at an advanced stage. Our results suggest that recent improvements in survival in men and women with adenocarcinoma are due at least partly to introduction of EGFR-TKIs into real-world practice, and to prescription based on appropriate patient selection following introduction of EGFR mutation testing into real-world practice in Japan.

308P Phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small cell lung cancer in Japan (SAMURAI study)

The standard of treatment for patients with unresectable, locally advanced NSCLC (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab. Although phase II studies in Japan have shown high efficacy and good tolerability of CRT with cisplatin + S-1 (SP), no prospective study using durvalumab after SP-based CRT has been reported. Thus, we conducted a phase II study using durvalumab after SP-based CRT for LA-NSCLC. The primary analysis was already presented in IASLC Asia 2022. Here, we report the additional results.

P28-6 Real-world evidence of crizotinib for ROS1-tested patients with non-small cell lung cancer in Japan

This study aims to reveal the use of crizotinib for ROS1-tested patients with non-small cell lung cancer (NSCLC) in Japanese real-world by investigating the duration of treatment (DOT) and treatment pattern of crizotinib.

Real-world outcomes of pembrolizumab monotherapy in non-small cell lung cancer in Japan: A post-marketing surveillance.

This post‐marketing surveillance (PMS) was initiated in Japan to identify factors affecting the safety and effectiveness of pembrolizumab monotherapy in patients with advanced non‐small cell lung cancer (NSCLC) with programmed cell death ligand‐1 (PD‐L1) expression. This PMS was conducted from December 2016 to June 2019 at 717 centers across Japan. Patients with unresectable advanced/recurrent NSCLC who received pembrolizumab monotherapy as first‐line (1L) treatment for PD‐L1‐expressing tumors (Tumor Proportion Score [TPS] ≥ 50%) or second‐line or later (2L+) treatment for tumors with PD‐L1 TPS ≥ 1% were enrolled and followed up for 1 year. Of 2805 registered patients, 2740 and 2400 comprised the safety and effectiveness analysis sets, respectively. The median age (range) was 69 (27–92) years; 55.7% and 29.2% of patients experienced treatment‐related adverse events and adverse events of special interest (AEOSIs), respectively. More common AEOSIs included interstitial lung disease, endocrine disorders, liver dysfunction, colitis/severe diarrhea, infusion reactions, and severe skin disorders. The frequency of experiencing ≥2 AEOSIs was low (1L, 6.5%; 2L+, 2.8%). Most AEOSIs occurred within 150 days after initiation of pembrolizumab monotherapy. At 1‐year follow‐up, the objective response rate was 39.2% (1L, 51.5%; 2L+, 30.0%). In conclusion, the 1‐year safety and effectiveness of pembrolizumab monotherapy in patients with unresectable advanced/recurrent NSCLC as 1L treatment for tumors with PD‐L1 TPS ≥ 50% and 2L+ treatment for tumors with PD‐L1 TPS ≥ 1% were similar to those reported in phase 2/3 trials.

Prospective analysis of factors precluding the initiation of durvalumab from an interim analysis of a phase II trial of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small cell lung cancer in Japan (SAMURAI study).

Background:The standard of care for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC trial. Disease progression and pneumonitis were reported as the main reasons to preclude the initiation of durvalumab in multiple retrospective studies. However, the transition rate and the reasons for failure to proceed to consolidation therapy with durvalumab after CRT were not evaluated prospectively. Although phase II studies in Japan have shown high efficacy and tolerability of CRT with cisplatin + S-1 (SP), no prospective study using durvalumab after SP-based CRT has yet been reported. We therefore conducted a phase II study to verify the efficacy and safety of durvalumab following SP-based CRT. In this interim analysis, we report the transition rate and the reasons for its failure.Methods:In treatment-naïve LA-NSCLC, cisplatin (60 mg/m2, day 1) and S-1 (80–120 mg/body, days 1–14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab every 2 weeks for up to 12 months. The primary endpoint was 12 month progression-free survival rate.Results:Fifty-nine patients were enrolled, of whom 86.4% (51/59) proceeded to durvalumab. All of them initiated durvalumab within 42 days after CRT [median 18 days (range: 3–38)], including 27.5% (14/51) in <14 days. Common reasons for failure to proceed to durvalumab were disease progression (2/59, 3.4%) and adverse events (6/59, 10.2%). Among the latter cases, four resumed treatment and proceeded to durvalumab within 42 days on off-protocol. The objective response rate and the disease control rate were 62.7% and 93.2%, respectively. The incidences of ⩾grade 3 pneumonitis, febrile neutropenia, and esophagitis were 0%, 8.5%, and 3.4%, respectively.Conclusion:Regarding durvalumab after CRT, this interim analysis of the SAMURAI study clarified the high transition rate, early introduction, and reasons for failure to proceed to consolidation therapy, which were not determined in the PACIFIC trial.Trial registration:Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.

POSC162 Cost Effectiveness Analysis of Nivolumab Plus Ipilimumab Therapy in Patients with Advanced Non-Small Cell Lung Cancer in Japan

This study aimed to evaluate the cost-effectiveness of combination therapy of nivolumab plus ipilimumab (NIV+IPI) for patients with advanced non-small-cell lung cancer (NSCLC), comparing with platinum-doublet chemotherapy in Japanese settings. A partitioned survival model was developed to predict costs and quality-adjusted life years (QALYs) in a NIV+IPI arm and a chemotherapy arm. Data on overall survival and progression-free survival was derived from the CheckMate 227 trial. Cost estimates were based on Japanese healthcare system perspective, by using real world data, JMDC claims database. Utilities were derived from published sources outside Japan. The incremental cost-effectiveness ratio (ICER) of NIV+IPI therapy compared with chemotherapy was estimated. A subgroup analysis on the level of PD-L1 expression (≥1% or not) was conducted. In addition, deterministic sensitivity analysis was performed to assess the uncertainty in parameter settings. Compared with chemotherapy, NIV+IPI therapy incurred an additional cost of USD166,984 and conferred an additional 0.81 QALY, which resulted in an ICER of USD205,141/QALY gained. Contrary to prior expectations, the ICER of patients with a PD-L1 expression level ≥1% was higher than that of patients with a PD-L1 expression level <1% (USD241,734/QALY and USD129,288/QALY, respectively). Sensitivity analyses showed a relatively robust result that the ICERs remined higher than a Japanese price adjustment threshold of USD75,000/QALY over the full range of model parameters. The combination therapy of nivolumab plus ipilimumab as first-line therapy would not be cost-effective under a willingness-to-pay threshold of USD75,000/QALY. However, a better cost-effectiveness was found in the subgroup with a PD-L1 expression level <1%, which needs further research to elucidate the heterogeneity and specific biological mechanisms.

368P Real-world characteristics, treatment, and outcomes of stage III non-small cell lung cancer in Japan: SOLUTION study

368P Real-world characteristics, treatment, and outcomes of stage III non-small cell lung cancer in Japan: SOLUTION study

Treatment Sequencing in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer in Japan: A Real-World Observational Study.

The anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) alectinib was approved in Japan in 2014 for the treatment of ALK fusion gene-positive advanced non-small cell lung cancer (NSCLC). With the approvals of crizotinib in 2012 and ceritinib in 2017, Japan became the first country with multiple ALK TKIs available for first-line or later use in patients with ALK-positive advanced NSCLC. Here, we collected and evaluated real-world data on ALK TKI clinical usage patterns and sequencing in patients with ALK-positive NSCLC in Japan. This retrospective observational study used the Japanese Medical Data Vision database to analyze data from patients with a confirmed diagnosis of lung cancer who visited a healthcare facility in the database between April 2010 and March 2017, underwent an ALK test, received a prescription for an ALK TKI, and were at least 18years old as of the date of the first ALK TKI prescription. There were no exclusion criteria. Descriptive analyses of demographics, baseline characteristics, ALK TKI treatment patterns and sequences, non-ALK TKI treatments received before, during, and after ALK TKI treatment, and treatment durations were reported. A total of 378 patients met the inclusion criteria and were evaluated in mutually exclusive groups of patients receiving one, two, or three ALK TKIs. The initial ALK TKI prescribed was crizotinib for 52.1% of patients and alectinib for 47.9% of patients; however, the proportion of patients receiving alectinib as the initial ALK TKI increased over time following the Japanese approval of alectinib in 2014. Of the 117 patients who received two or three ALK TKIs, 106 received crizotinib as the first ALK TKI and 11 received alectinib. Before the date of the patient's first ALK TKI prescription, 153 of 378 patients (40.5%) had received chemotherapy. Of 104 patients who discontinued ALK therapy, 46.2% received chemotherapy and 5.8% received immunotherapy as their next treatment. At the time of this analysis, most patients who received more than one ALK TKI received crizotinib as the initial ALK TKI. Additional ALK TKIs have since been approved in Japan as first-line or later therapeutic options for patients with ALK-positive NSCLC, but the optimal sequence of ALK TKI usage remains undetermined. As new data continue to emerge, additional research will be warranted to evaluate ALK TKI sequences that do not include crizotinib as the first therapy in this patient population.

Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line treatment for stage IV squamous non-small cell lung cancer: A phase 1b and randomized, open-label, multicenter, phase 2 trial in Japan

ObjectivesThis open-label, multicenter, phase 1b/2 study assessed necitumumab plus gemcitabine and cisplatin (GC + N) in patients with previously untreated squamous non-small cell lung cancer in Japan. Materials and methodsThe phase 1b part determined the gemcitabine dose for the phase 2 part, in which patients were randomized 1:1 to GC + N or gemcitabine and cisplatin (GC) (gemcitabine 1250 mg/m2 on days 1 and 8; cisplatin 75 mg/m2 on day 1 of maximum four 3-week cycles; nectimumab 800 mg on days 1 and 8 of a 3-week cycle continued until progressive disease or unacceptable toxicity). The primary endpoint of the phase 2 part was overall survival. ResultsIn the phase 2 part, 181 patients received GC + N (N = 90) or GC (N = 91). Overall survival was significantly improved with GC + N versus GC (median, 14.9 months vs 10.8 months; hazard ratio [HR] = 0.66, 95% CI: 0.47 – 0.93, p = 0.0161). Improvements were also observed in progression-free survival (median, 4.2 months vs 4.0 months; HR = 0.56; p = 0.0004) and objective response rate (51% vs 21%; p < 0.0001). Survival was also significantly prolonged with GC + N versus GC for patients with epidermal growth factor receptor-positive tumors. Grade ≥3 treatment-emergent adverse events at ≥5% higher incidence with GC + N than GC were neutrophil count decreased (42% vs 35%), febrile neutropenia (12% vs 3%), decreased appetite (11% vs 4%), and dermatitis acneiform (6% vs 0%). ConclusionGC + N is well tolerated and has significant and clinically meaningful treatment benefit in the first-line treatment of patients with squamous non-small cell lung cancer in Japan. Clinicaltrials.gov identifier: NCT01763788.

P3.01-40 Treatment of Super Elderly Patients for Non-Small Cell Lung Cancer in Japan

P3.01-40 Treatment of Super Elderly Patients for Non-Small Cell Lung Cancer in Japan

O1-18-1 - Large-scale nationwide genomic screening system for small cell lung cancer in Japan (LC-SCRUM-Japan)

O1-18-1 - Large-scale nationwide genomic screening system for small cell lung cancer in Japan (LC-SCRUM-Japan)

Large-scale nationwide genomic screening system for small cell lung cancer in Japan (LC-SCRUM-Japan).

8572Background: Recent genomic analyses of small-cell lung cancer (SCLC) have provided insights into novel therapeutic targets such as the PI3K pathway. Thus, we prospectively analyzed clinical sam...

O2-4-2 - A nationwide genomic screening project for small cell lung cancer in Japan (LC-SCRUM-Japan)

O2-4-2 - A nationwide genomic screening project for small cell lung cancer in Japan (LC-SCRUM-Japan)