Final Survival Outcomes With Ramucirumab Plus Erlotinib Versus Placebo Plus Erlotinib in Patients With Untreated -Mutated Metastatic NSCLC: RELAY Japanese Subset.

Introduction: Significant improvement in progression-free survival (PFS; primary end point) was reported in the phase 3 RELAY study with ramucirumab (RAM) plus erlotinib (ERL) versus placebo (PL) in untreated -mutated NSCLC (hazard ratio [HR] = 0.59, 95% confidence interval [CI]: 0.46-0.

Real-world safety and effectiveness of entrectinib in Japanese patients with ROS1 gene fusion-positive, unresectable, advanced/recurrent non-small cell lung cancer: Post-marketing surveillance.

Objectives: To evaluate the safety and effectiveness of entrectinib, an orally-administered potent multi-kinase inhibitor, for the treatment of proto-oncogene tyrosine-protein kinase-1 (ROS1) gene fusion-positive, unresectable, advanced/recurrent non-small cell lung cancer (NSCLC) in Japan.

Materials And Methods: Patients with ROS1 gene fusion-positive, unresectable, advanced/recurrent NSCLC who initiated entrectinib therapy were enrolled in this all-case post marketing surveillance between February 21, 2020 and November 30, 2021. Outcomes were to identify the: (1) type and onset of initial cognitive disorder and ataxia during entrectinib therapy; (2) status of treatment and outcome of drug-related cognitive disorder and ataxia events; (3) incidence of other adverse drug reactions (ADRs) of safety concern: cognitive disorder and/or ataxia, cardiac disorder (excluding QT interval prolongation), QT interval prolongation, syncope, and interstitial lung disease; (4) incidence of serious adverse events (AEs) and ADRs; and (5) effectiveness.

RELAY: Final Overall Survival for Erlotinib Plus Ramucirumab or Placebo in Untreated, EGFR-Mutated Metastatic NSCLC.

Introduction: RELAY, a global double-blind, placebo-controlled phase 3 study (NCT02411448) found statistically significant improvement in progression-free survival (primary end point) for ramucirumab (RAM) plus erlotinib (ERL) (RAM + ERL) in patients with untreated EGFR-mutated metastatic NSCLC (hazard ratio [HR] = 0.59, 95% confidence interval [CI]: 0.46-0.

Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from the open-label, phase 2 GEOMETRY mono-1 trial.

Background: Capmatinib has previously shown activity in treatment-naive and previously treated patients with non-small-cell lung cancer (NSCLC) and a MET exon 14-skipping mutation (METex14). Here, we report the final outcomes from the phase 2 GEOMETRY mono-1 study with an aim to provide further evidence for the activity of capmatinib.

Methods: In this non-randomised, multi-cohort, open-label, phase 2 trial conducted in 152 centres and hospitals in 25 countries, with patients treated in 95 centres in 20 countries, eligible patients (aged ≥18 years) with MET-dysregulated, EGFR wild-type, and ALK rearrangement-negative advanced NSCLC (stage IIIB/IV) and an Eastern Cooperative Oncology Group performance status of 0 or 1 were assigned to cohorts (1a, 1b, 2, 3, 4, 5a, 5b, 6 and 7) based on their MET status (METex14 or MET amplification) and previous therapy lines.

Phase 2 trial of crizotinib in Japanese patients with advanced NSCLC harboring a MET gene alteration: a Co-MET study.

Background: MET exon 14 skipping mutations occur in 3-4% and MET high amplifications occur in < 1% of patients with non-small-cell lung cancer (NSCLC). Crizotinib, a selective ATP-competitive small-molecule inhibitor of c-Met, ALK, and ROS1 tyrosine kinases, has shown activity in cancer models with various types of MET activation.

Methods: The Co-MET study is a single-arm phase 2 trial to assess the safety and efficacy of crizotinib in MET inhibitor-naïve patients with advanced NSCLC harboring MET exon 14 skipping mutation (cohort 1) or high MET gene copy number of ≥ 7 (cohort 2).

Phase 1 study of pembrolizumab plus chemotherapy in Japanese patients with extensive-stage small-cell lung cancer.

Background: Part E of the KEYNOTE-011 (NCT01840579) study assessed the safety and antitumor activity of pembrolizumab plus platinum-etoposide chemotherapy in Japanese patients with previously untreated extensive-stage small-cell lung cancer (ES-SCLC).

Methods: Patients received 4 cycles of pembrolizumab (200 mg) every 3 weeks in combination with cisplatin (75 mg/m) and etoposide (100 mg/m; days 1, 2, 3) in cohort 1; with carboplatin (AUC 5 mg/mL/min) and etoposide (100 mg/m; days 1, 2, 3) in cohort 2; or with cisplatin/etoposide and pegfilgrastim (3.6 mg; cycle 1, day 4) in cohort 3.

Impact of ramucirumab plus erlotinib on circulating cell-free DNA from patients with untreated metastatic non-small cell lung cancer with -activating mutations (RELAY phase 3 randomized study).

Background: An exploratory, proof-of-concept, liquid biopsy addendum to examine biomarkers within cell-free DNA (cfDNA) in the RELAY phase 3, randomized, double-blind, placebo-controlled study was conducted. RELAY showed improved progression-free survival (PFS) with ramucirumab (RAM), a human immunoglobulin G1 vascular endothelial growth factor receptor 2 antagonist, plus erlotinib (ERL), a tyrosine kinase inhibitor, compared with placebo (PL) plus ERL.

Methods: Treatment-naïve patients with endothelial growth factor receptor ()-mutated metastatic non-small cell lung cancer were randomized (1:1) to RAM + ERL or PL + ERL.

Brigatinib in Japanese patients with ALK-positive non-small-cell lung cancer: Final results of the phase 2 J-ALTA trial.

The phase 2, single-arm, multicenter, open-label J-ALTA study evaluated the efficacy and safety of brigatinib in Japanese patients with advanced ALK+ non-small-cell lung cancer (NSCLC). One expansion cohort of J-ALTA enrolled patients previously treated with ALK tyrosine kinase inhibitors (TKIs); the main cohort included patients with prior alectinib ± crizotinib. The second expansion cohort enrolled patients with TKI-naive ALK+ NSCLC.

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.

Impact of the pretreatment prognostic nutritional index on the survival after first-line immunotherapy in non-small-cell lung cancer patients.

Background: Immunotherapy has become a standard-of-care for patients with non-small-cell lung cancer (NSCLC). Although several biomarkers, such as programmed cell death-1, have been shown to be useful in selecting patients likely to benefit from immune checkpoint inhibitors (ICIs), more useful and reliable ones should be investigated. The prognostic nutritional index (PNI) is a marker of the immune and nutritional status of the host, and is derived from serum albumin level and peripheral lymphocyte count.

Quality of life with docetaxel plus cisplatin versus paclitaxel plus carboplatin in patients with completely resected non-small cell lung cancer: quality of life analysis of TORG 0503.

Purpose: The TORG0503 study was undertaken to select a preferred platinum-based third-generation regimen for patients with completely resected non-small cell lung cancer (NSCLC). This study aimed to describe the quality of life (QOL) analysis of that study.

Methods: Patients with completely resected NSCLC were randomized to receive three cycles of docetaxel plus cisplatin (DC) or paclitaxel plus carboplatin (PC) on day 1 every 3 weeks.

Tumor plasticity and therapeutic resistance in oncogene-addicted non-small cell lung cancer: from preclinical observations to clinical implications.

The identification of actionable targets in oncogene-addicted non-small cell lung cancer (NSCLC) has fueled biomarker-directed strategies, especially in advanced stage disease. Despite the undeniable success of molecular targeted therapies, duration of clinical response is relatively short-lived. While extraordinary efforts have defined the complexity of tumor architecture and clonal evolution at the genetic level, not equal interest has been given to the dynamic mechanisms of phenotypic adaptation engaged by cancer during treatment.

TRUST-II: a global phase II study of taletrectinib in -positive non-small-cell lung cancer and other solid tumors.

Crizotinib and entrectinib have been approved to treat fusion-positive (ROS1) non-small-cell lung cancer. However, unmet needs remain, including treatment of patients with resistance mutations, efficacy in brain metastasis and avoidance of neurological side effects. Taletrectinib was designed to: improve efficacy; overcome resistance to first-generation ROS1 inhibitors; and address brain metastasis while conferring fewer neurological adverse events.

Case report: Success of tepotinib therapy in overcoming resistance to osimertinib in a patient with EGFR-mutant lung adenocarcinoma with a potential acquired MET exon 14 skipping mutation.

Osimertinib is a standard therapy for the treatment of advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor gene () mutations, but most patients with -mutant NSCLC develop secondary resistance to osimertinib. Mesenchymal-epithelial transition gene () alterations and oncogene fusions have been identified as the most common mechanisms of resistance to osimertinib. However, exon 14 skipping mutation (ex14del) as an acquired resistance to osimertinib has rarely been reported.

Final Overall Survival, Safety, and Quality of Life Results From a Phase 2 Study of Crizotinib in East Asian Patients With -Positive Advanced NSCLC.

Introduction: Crizotinib provided meaningful clinical benefit in the initial analysis of a phase 2 study in East Asian patients with advanced -positive NSCLC (NCT01945021). Nevertheless, overall survival (OS) data were immature. Here, we present the final OS, quality of life (QoL), and safety data after an additional 3 years of follow-up.

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.

Brigatinib in Japanese patients with tyrosine kinase inhibitor-naive ALK-positive non-small cell lung cancer: first results from the phase 2 J-ALTA study.

Background: We evaluated the safety and efficacy of the anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) brigatinib in Japanese patients with TKI-naive ALK-positive non-small cell lung cancer (NSCLC) from the phase 2, open-label, single-arm, multicenter J-ALTA study.

Methods: In the TKI-naive cohort of J-ALTA, the primary end point was independent review committee (IRC)-assessed 12-month progression-free survival (PFS). Secondary end points included objective response rate (ORR), intracranial response, overall survival (OS), and safety.

Phase II study of S-1 plus cisplatin with concurrent radiotherapy for locally advanced thymic carcinoma: Results of the LOGIK1605/JART-1501 study.

Background: Combination chemotherapy is used to treat advanced thymic carcinoma; however, the effects are insufficient.

Methods: Previously untreated patients with unresectable locally advanced thymic carcinoma received two cycles of 80 mg/m /day S-1 orally on days 1-14 plus 60 mg/m /day cisplatin intravenously on day 1, and concurrent radiotherapy (60 Gy).

Results: Three patients were enrolled into the study.

Erlotinib with or without bevacizumab as a first-line therapy for patients with advanced nonsquamous epidermal growth factor receptor-positive non-small cell lung cancer: Exploratory subgroup analyses from the phase II JO25567 study.

Background: In the phase II JO25567 study (JapicCTI-111390), erlotinib plus bevacizumab demonstrated a significant clinical benefit in Japanese patients with epidermal growth factor receptor mutation-positive (EGFR+) non-small cell lung cancer (NSCLC). Here, we present an exploratory analysis investigating the impact of baseline pleural/pericardial effusion (PPE) on patient outcomes.

Methods: Patients with stage IIIB/IV or postoperative recurrent EGFR+ NSCLC were randomized 1:1 to receive erlotinib (150 mg/day) plus bevacizumab (15 mg/kg every 3 weeks) or erlotinib monotherapy.

Survival benefit of using pemetrexed for EGFR mutation-positive advanced non-small-cell lung cancer in a randomized phase III study comparing gefitinib to cisplatin plus docetaxel (WJTOG3405).

Background: Pemetrexed is common cytotoxic chemotherapy among non-squamous non-small cell lung cancer (non-Sq-NSCLC) patients; however, among epidermal growth factor receptor (EGFR)-positive lung cancer, there is no clear evidence to support the efficacy of sequential treatment with pemetrexed.

Material And Methods: We performed a post-hoc analysis of subsequent chemotherapies among 144 patients who received the post-protocol treatment in the phase III trial WJTOG 3405 comparing gefitinib to cisplatin plus docetaxel, and analyzed the effect of pemetrexed on overall survival (OS).

Results: Patients with treatment including pemetrexed exhibited significantly longer OS in comparison to those without pemetrexed; the median OS in the pemetrexed + and pemetrexed- patients were 40.