Real-world status of multimodal treatment of Stage IIIA-N2 non-small cell lung cancer in Japan: Results from the SOLUTION study, a non-interventional, multicenter cohort study.

Objectives: There is limited consensus on resectability criteria for Stage IIIA-N2 non-small cell lung cancer (NSCLC). We examined the patient characteristics, N2 status, treatment decisions, and clinical outcomes according to the treatment modality for Stage IIIA-N2 NSCLC in Japan.

Materials And Methods: Patients with Stage IIIA-N2 NSCLC in Japan were consecutively registered in the SOLUTION study between 2013 and 2014.

Randomized Phase II Trial of Amrubicin Plus Irinotecan Versus Cisplatin Plus Irinotecan in Chemo-naïve Patients With Extensive-Disease Small-Cell Lung Cancer: Results of the Japan Multinational Trial Organization (JMTO) LC 08-01.

Background: We conducted a randomize phase II study to evaluate the efficacy and safety of topoisomerase II inhibitor amrubicin plus topoisomerase I inhibitor irinotecan (AI) compared with cisplatin plus irinotecan (PI) as first-line therapy in patients with extensive-disease (ED) small-cell lung cancer (SCLC).

Patients And Methods: Chemo-naïve patients with pathologically proven ED-SCLC (including limited disease (LD) SCLC with malignant effusion) were enrolled. Patients were randomized 1:1 to receive either AI (amrubicin 90mg/m on day 1 and irinotecan 50mg/m on days 1 and 8 of a 21-day cycle) or PI (cisplatin 60mg/m on day 1 and irinotecan 60mg/m on days 1, 8 and 15 of a 28-day cycle).

Long-term experience with tepotinib in Japanese patients with MET exon 14 skipping NSCLC from the Phase II VISION study.

Tepotinib is a highly selective MET tyrosine kinase inhibitor (TKI) that has demonstrated robust and durable clinical activity in patients with MET exon 14 (METex14) skipping non-small-cell lung cancer (NSCLC). In the Phase II VISION study, patients received oral tepotinib 500 mg once daily. The primary endpoint was an objective response by an independent review committee (IRC) according to RECIST v1.

Neoadjuvant nivolumab plus chemotherapy in resectable non-small-cell lung cancer in Japanese patients from CheckMate 816.

In the open-label, phase III CheckMate 816 study (NCT02998528), neoadjuvant nivolumab plus chemotherapy demonstrated statistically significant improvements in event-free survival (EFS) and pathological complete response (pCR) versus chemotherapy alone in patients with resectable non-small-cell lung cancer (NSCLC). Here we report efficacy and safety outcomes in the Japanese subpopulation. Patients with stage IB-IIIA, resectable NSCLC were randomized 1:1 to nivolumab plus chemotherapy or chemotherapy alone for three cycles before undergoing definitive surgery within 6 weeks of completing neoadjuvant treatment.

A randomized phase III study of docetaxel alone versus docetaxel plus S-1 in patients with previously treated non-small cell lung cancer: JMTO LC09-01.

Background: This study evaluated the efficacy and safety of the combination chemotherapy of docetaxel plus S-1 in patients with previously treated non-small cell lung cancer (NSCLC) compared to docetaxel alone.

Methods: Patients with previously treated NSCLC were randomly assigned to docetaxel alone (arm A) or a combination of docetaxel and S-1 (arm B) for a maximum of four cycles. The primary endpoint was overall survival (OS).

Biomarker analysis of the phase II JO25567 study comparing erlotinib with or without bevacizumab in first-line advanced non-small-cell lung cancer.

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), such as erlotinib, are standard-of-care for patients with mutation-positive non-small-cell lung cancer (NSCLC), but most patients progress within 1 year. Previously, we demonstrated that erlotinib plus bevacizumab (EB) improved progression-free survival (PFS) in patients with -positive non-squamous NSCLC in the randomized JO25567 study. To understand this effect, we conducted comprehensive exploratory biomarker analyses.

Survival Impact of Second-Line Immune Checkpoint Inhibitors in Older Patients With Advanced Squamous-Cell NSCLC: Post Hoc Analysis of the CAPITAL Study.

Introduction: In the CAPITAL study, a randomized phase 3 study, wherein carboplatin plus nab-paclitaxel treatment was compared with docetaxel treatment for older patients with squamous-cell lung cancer, the former became the new standard of care for such patients. Our study aimed to evaluate whether the efficacy of second-line immune checkpoint inhibitors (ICIs) affected the primary analysis of overall survival (OS).

Methods: Herein, we performed a post hoc analysis of the impact of second-line ICIs on OS, safety in each group of participants aged more than 75 years, and intracycle nab-paclitaxel skip status.

Clinical benefit of platinum doublet combination therapy in older adults with advanced non-small cell lung cancer: A prospective multicenter study by the National Hospital Organization in Japan.

Background: Previous trials suggest that older adults with non-small cell lung cancer (NSCLC) derive benefit from platinum doublet combination therapy, but its superiority is controversial. Although geriatric assessment variables are used to assess the individual risk of severe toxicity and clinical outcomes in older patients, the standard first-line treatment is still debated. Therefore, we aimed to identify the risk factors for clinical outcomes in older patients with NSCLC.

Standard versus low-dose nab-paclitaxel in previously treated patients with advanced non-small cell lung cancer: A randomized phase II trial (JMTO LC14-01).

Background: Nab-paclitaxel (nab-PTX) has better transfer to tumor tissue than cremophor-based paclitaxel. It suggests that the optimum dose of nab-PTX might be lower than the dose and schedule that is widely used. We designed a randomized phase II trial to examine the clinical utility and safety of nab-PTX in patients with previously treated advanced non-small cell lung cancer (NSCLC).

Efficacy and safety of carboplatin with nab-paclitaxel versus docetaxel in older patients with squamous non-small-cell lung cancer (CAPITAL): a randomised, multicentre, open-label, phase 3 trial.

Background: In Japan, docetaxel, a cytotoxic monotherapy, is the standard drug administered to older patients with advanced non-small-cell lung cancer (NSCLC). Carboplatin plus nab-paclitaxel has shown a high objective response rate in patients with squamous histology and was suggested to improve overall survival in patients aged 70 years and older. The CAPITAL trial aimed to assess the safety and efficacy of carboplatin plus nab-paclitaxel versus docetaxel as first-line therapy for patients aged 70 years and older with advanced squamous NSCLC.

Predicting systemic therapy toxicity in older adult patients with advanced non-small cell lung cancer: A prospective multicenter study of National Hospital Organization in Japan.

Introduction: Previous studies have developed risk stratification schemas to assess systemic therapy toxicity. However, it is controversial which geriatric assessment variables should be used to assess the individual risk of severe treatment-associated toxicity in older adult patients.

Materials And Methods: Patients aged ≥70 years with advanced non-small cell lung cancer (NSCLC) treated at 24 National Hospital Organization institutions completed a pre-first-line systemic therapy assessment, including patient characteristics, treatment variables, laboratory test values, and geriatric assessment variables.

A randomized phase II study of docetaxel or pemetrexed with or without the continuation of gefitinib after disease progression in elderly patients with non-small cell lung cancer harboring EGFR mutations (JMTO LC12-01).

Background: Gefitinib (G) is a recommended molecular-targeted agent for elderly patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Docetaxel (Doc) and pemetrexed (Pem) have similar efficacies, and either is often used as the sole agent during treatment. The efficacy of continuing G after progressive disease (PD) develops has been reported.

Nintedanib plus chemotherapy for nonsmall cell lung cancer with idiopathic pulmonary fibrosis: a randomised phase 3 trial.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease implicated as an independent risk factor for lung cancer. However, optimal treatment for advanced lung cancer with IPF remains to be established. We performed a randomised phase 3 trial (J-SONIC) to assess the efficacy and safety of nintedanib plus chemotherapy (experimental arm) compared with chemotherapy alone (standard-of-care arm) for advanced nonsmall cell lung cancer (NSCLC) with IPF.

A multicenter, open-label, single-arm study of anamorelin (ONO-7643) in patients with cancer cachexia and low body mass index.

Background: Cancer cachexia is a syndrome characterized by anorexia and decreased body weight. This study evaluated the efficacy and safety of anamorelin, an orally active, selective ghrelin receptor agonist, in patients with cancer cachexia and a low body mass index (BMI).

Methods: This multicenter, open-label, single-arm study enrolled Japanese patients with non-small cell lung cancer or gastrointestinal cancer with cancer cachexia (BMI < 20 kg/m , involuntary weight loss > 2% in the last 6 months, and anorexia).

Deciphering the clinical features of heterogeneous stage III non-small cell lung cancer in Japanese real-world clinical practice: Expanded cohort of the SOLUTION study.

Objectives: To evaluate the actual treatment patterns with respective outcomes and the patient characteristics of stage III non-small cell lung cancer (NSCLC) in Japan.

Materials And Methods: Patients (aged ≥20 years at diagnosis) who were diagnosed with stage III NSCLC between January 2013 and December 2014 and underwent surgery, chemoradiotherapy (CRT), chemotherapy (CT), or radiotherapy (RT) at 11 institutions in Japan were consecutively registered in this retrospective, observational study (SOLUTION; UMIN000031385). Study measures included patient characteristics, first-line treatments, overall survival (OS), progression-free survival, objective response rate, and incidence of radiation-related adverse events.

Uncommon mutations conducted with osimertinib in patients with NSCLC: a study protocol of phase 2 study (UNICORN/TCOG1901).

Patients with uncommon mutated non-small-cell lung cancer (NSCLC) demonstrated lower clinical efficacy of first-generation EGFR-tyrosine kinase inhibitors compared with patients harboring common mutated NSCLC. The US FDA has approved afatinib for uncommon mutation positive NSCLC based on the pooled analysis in the first- or second-line setting. Osimertinib has limited evidence in the small sample sizes of phase 2 studies in any-line settings.

Health-Related Quality of Life Outcomes in Patients with Resected Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer Who Received Adjuvant Osimertinib in the Phase III ADAURA Trial.

Purpose: In the phase III ADAURA trial, adjuvant treatment with osimertinib versus placebo, with/without prior adjuvant chemotherapy, resulted in a statistically significant and clinically meaningful disease-free survival benefit in completely resected stage IB-IIIA EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). We report health-related quality of life (HRQoL) outcomes from ADAURA.

Patients And Methods: Patients randomized 1:1 received oral osimertinib 80 mg or placebo for 3 years or until recurrence/discontinuation.

Retrospective analysis of long-term survival factors in patients with advanced non-small cell lung cancer treated with nivolumab.

Background: Nivolumab, an immune checkpoint inhibitor (ICI), has changed the treatment paradigm for advanced non-small cell lung cancer (NSCLC). However, factors associated with long-term survival in NSCLC patients treated with ICIs remain unknown. This study aimed to evaluate patient characteristics and clinical laboratory changes related to long-term survival in NSCLC patients treated with nivolumab, using real-world data.

Randomized Phase III Study of Gefitinib Versus Cisplatin Plus Vinorelbine for Patients With Resected Stage II-IIIA Non-Small-Cell Lung Cancer With Mutation (IMPACT).

Purpose: To investigate the efficacy of gefitinib as an adjuvant therapy for non-small-cell lung cancer patients with mutation.

Patients And Methods: IMPACT (WJOG6410L; University Hospital Medical Information Network Clinical Trials Registry: UMIN000006252), a randomized, open-label, phase III study, included patients with completely resected pathologic stage II-III non-small-cell lung cancer harboring mutations (exon 19 deletion or L858R) during September 2011 to December 2015. Patients were randomly assigned to receive gefitinib (250 mg once daily) for 24 months or cisplatin (80 mg/m on day 1) plus vinorelbine (25 mg/m on days 1 and 8; cis/vin) once every 3 weeks for four cycles.

Efficacy and safety of ramucirumab plus docetaxel in older patients with advanced non-small cell lung cancer: A multicenter retrospective cohort study.

Objective: Ramucirumab (RAM) plus Docetaxel (DOC) is one of the standard treatments after first-line treatment failure in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the efficacy and safety of RAM plus DOC in older patients. We aimed to clarify these and elucidate the prognostic factors.