Impact of select actionable genomic alterations on efficacy of neoadjuvant immunotherapy in resectable non-small cell lung cancer.

Background: Neoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy of neoadjuvant ICIs remains unclear. We report the influence of AGAs on treatment failure (TF) in patients with resectable NSCLC treated with neoadjuvant ICIs.

Brief Report: Clinical Response, Toxicity, and Resistance Mechanisms to Osimertinib Plus MET Inhibitors in Patients With EGFR-Mutant MET-Amplified NSCLC.

Introduction: amplification is a known resistance mechanism to tyrosine kinase inhibitor (TKI) treatment in -mutant NSCLC. Dual EGFR-MET inhibition has been reported with success in overcoming such resistance and inducing clinical benefit. Resistance mechanisms to dual EGFR-MET inhibition require further investigation and characterization.

Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy.

Purpose: To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy.

Patients And Methods: Eligible patients had a performance status 0 to 2, previous treatment with one prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Patients received pemetrexed 500 mg/m intravenously (IV) day 1 with vitamin B, folic acid, and dexamethasone or docetaxel 75 mg/m IV day 1 with dexamethasone every 21 days.

Safety, tolerability, and clinical activity of selinexor in combination with pembrolizumab in treatment of metastatic non-small cell lung cancer.

Background: In lung cancer, overexpression of nuclear export proteins can result in inactivation of critical tumor suppressor proteins and cell-cycle regulators. Selective suppression of nuclear export proteins has immunomodulatory activities. Here, clinical safety and early efficacy data are presented on the combination of pembrolizumab and an oral selective nuclear export inhibitor, selinexor, for the treatment of metastatic non-small cell lung cancer (mNSCLC).

Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial.

Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEOSTAR trial testing neoadjuvant Nivo+CT and Ipi+Nivo+CT with major pathologic response (MPR) as the primary endpoint.

Integration of Remote Symptom and Biometric Monitoring Into the Care of Adult Patients With Cancer Receiving Chemotherapy-A Decentralized Feasibility Pilot Study.

Purpose: Although electronic patient-reported outcomes (ePROs) are efficacious in symptom management, much is unknown about the utility of vital signs surveillance. We examined the feasibility of a remote patient monitoring platform that integrates ePROs and biometrics into the ambulatory management of symptom burden.

Methods: Using a decentralized workflow, patients with gastrointestinal or thoracic cancer were approached for a 1-month study.

Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity.

We report a phase II study of 50 advanced non-small cell lung cancer (NSCLC) patients with point mutations or insertions in EGFR exon 20 treated with poziotinib (NCT03066206). The study achieved its primary endpoint, with confirmed objective response rates (ORRs) of 32% and 31% by investigator and blinded independent review, respectively, with a median progression-free survival of 5.5 months.

Poziotinib for Patients With Exon 20 Mutant Non-Small-Cell Lung Cancer: Results From a Phase II Trial.

Purpose: Targeted therapies against non-small-cell lung cancer (NSCLC) harboring mutations remain an unmet need. In this study, we assessed the efficacy and safety of poziotinib in patients with exon 20 mutant advanced NSCLC in a single-arm, open-label, phase II study.

Patients And Methods: Patients with advanced exon 20 mutant NSCLC were enrolled to receive poziotinib at a dose of 16 mg/d for 28-day cycles.

High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: Results of a phase II trial.

Aim: To report early findings from a phase II trial of high-dose radiotherapy (HD-RT) with or without low-dose RT (LD-RT) for metastatic cancer.

Methods: Eligible patients had metastatic disease that progressed on immunotherapy within 6 months. Patients were given either HD-RT (20-70 Gy total; 3-12.

Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial.

Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy.

Toxicity and Survival After Intensity-Modulated Proton Therapy Versus Passive Scattering Proton Therapy for NSCLC.

Objective: Although intensity-modulated radiation therapy (IMPT) is dosimetrically superior to passive scattering proton therapy (PSPT) for locally advanced NSCLC (LA-NSCLC), direct comparisons of clinical outcomes are lacking. Here, we compare toxicity profiles and clinical outcomes after IMPT versus PSPT for LA-NSCLC.

Methods: This is a nonrandomized, comparative study of two independent cohorts with LA-NSCLC (stage II-IIIB, stage IV with solitary brain metastasis) treated with concurrent chemotherapy and proton beam therapy.

Programmed Death-Ligand 1 Heterogeneity and Its Impact on Benefit From Immune Checkpoint Inhibitors in NSCLC.

Introduction: Programmed death-ligand 1 (PD-L1) expression may vary in different disease sites and at different time points of the disease course. We aimed to investigate PD-L1 heterogeneity and its usefulness as a predictive value for immune checkpoint inhibitor (ICI) therapy in patients with NSCLC.

Methods: PD-L1 expression was analyzed in 1398 patients with NSCLC.

A Phase I/II Study of Neoadjuvant Cisplatin, Docetaxel, and Nintedanib for Resectable Non-Small Cell Lung Cancer.

Purpose: Nintedanib enhances the activity of chemotherapy in metastatic non-small cell lung cancer (NSCLC). In this phase I/II study, we assessed safety and efficacy of nintedanib plus neoadjuvant chemotherapy, using major pathologic response (MPR) as primary endpoint.

Patients And Methods: Eligible patients had stage IB (≥4 cm)-IIIA resectable NSCLC.

Phase II Trial of Cediranib in Combination With Cisplatin and Pemetrexed in Chemotherapy-Naïve Patients With Unresectable Malignant Pleural Mesothelioma (SWOG S0905).

Purpose: Antiangiogenic agents combined with chemotherapy have efficacy in the treatment of unresectable malignant pleural mesothelioma (MPM). Cediranib (AstraZeneca, Cheshire, United Kingdom), a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, demonstrated therapeutic potential in a prior phase I trial. We evaluated a phase II trial for efficacy.

Bayesian Adaptive Randomization Trial of Passive Scattering Proton Therapy and Intensity-Modulated Photon Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer.

Purpose This randomized trial compared outcomes of passive scattering proton therapy (PSPT) versus intensity-modulated (photon) radiotherapy (IMRT), both with concurrent chemotherapy, for inoperable non-small-cell lung cancer (NSCLC). We hypothesized that PSPT exposes less lung tissue to radiation than IMRT and thereby reduces toxicity without compromising tumor control. The primary end points were grade ≥ 3 radiation pneumonitis (RP) and local failure (LF).

Simultaneous Integrated Boost for Radiation Dose Escalation to the Gross Tumor Volume With Intensity Modulated (Photon) Radiation Therapy or Intensity Modulated Proton Therapy and Concurrent Chemotherapy for Stage II to III Non-Small Cell Lung Cancer: A Phase 1 Study.

Purpose: To establish, in the phase 1 portion of a prospective phase 1/2 study, the maximum tolerated dose of image guided intensity modulated radiation therapy (IMRT) or proton therapy (IMPT), both with a simultaneous integrated boost (SIB), for patients with stage II to IIIB non-small cell lung cancer receiving concurrent chemoradiation therapy.

Methods And Materials: Patients had pathologically proven non-small cell lung cancer, either unresectable stage II to IIIB disease or recurrent disease after surgical resection, and could tolerate concurrent chemoradiation. Radiation doses were selectively escalated to the SIB volume (internal gross tumor volume + 5-mm margin), and the dose to the planning target volume (internal gross tumor volume + 8-mm margin for clinical target volume + 5 mm) was kept at 60 Gy [cobalt gray equivalent (CGE)] over 30 fractions.

Induction Cisplatin Docetaxel Followed by Surgery and Erlotinib in Non-Small Cell Lung Cancer.

Background: Data from meta-analyses support the use of induction or adjuvant platinum-based chemotherapy for locally advanced non-small cell lung cancers (NSCLCs). This phase 2 study assessed the role of induction cisplatin and docetaxel followed by surgery in patients with resectable stage I to III NSCLCs, followed by 12 months of adjuvant erlotinib.

Methods: Patients with resectable stage I to III NSCLCs received cisplatin 80 mg/m, docetaxel 75 mg/m every 21 days for 3 cycles, followed by surgery, followed by adjuvant erlotinib for 12 months.

Response rates to single-agent chemotherapy after exposure to immune checkpoint inhibitors in advanced non-small cell lung cancer.

Introduction: Exploratory analysis of clinical trials in various tumor types have demonstrated potential improvements in overall response rate (ORR) to chemotherapy after exposure to vaccine-based immunotherapy. The objective of this retrospective study was to determine if single-agent chemotherapy (3rd-line or beyond) would yield improved ORR when given after exposure to programmed death-(ligand)1 inhibitors (anti-PD1) in metastatic non-small cell lung cancer (NSCLC).

Materials And Methods: We queried the Thoracic GEMINI database of MD Anderson Cancer Center for patients treated between 06/12 and 11/16 who received at least one single-agent chemotherapy as 3rd-line or beyond, following progression after platinum-based chemotherapy and anti-PD1.

The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer.

Purpose: By applying the principles of real-time biopsy, biomarker-based, adaptively randomized studies in non-small-cell lung cancer (NSCLC) established by the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, we conducted BATTLE-2 (BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer), an umbrella study to evaluate the effects of targeted therapies focusing on KRAS-mutated cancers.

Patients And Methods: Patients with advanced NSCLC (excluding sensitizing EGFR mutations and ALK gene fusions) refractory to more than one prior therapy were randomly assigned, stratified by KRAS status, to four arms: (1) erlotinib, (2) erlotinib plus MK-2206, (3) MK-2206 plus AZD6244, or (4) sorafenib. Tumor gene expression profiling-targeted next-generation sequencing was performed to evaluate predictive and prognostic biomarkers.

Biomarkers/Molecular Targets, Immunotherapy, and Treatments for Non-Small Cell Lung Cancer.

For decades, the prognosis for patients with advanced-stage non-small cell lung cancer (NSCLC) was bleak, with chemotherapy offering limited benefit and much toxicity. Now, with mutational testing, new generations of targeted therapies, and emerging immunotherapies, the treatment horizon for these patients has greatly expanded. In this article, the authors review molecular targets, biomarkers, as well as immune checkpoint inhibitors, which are having a major impact on the management of this patient population.

Phase I study of IMGN901, a CD56-targeting antibody-drug conjugate, in patients with CD56-positive solid tumors.

Background IMGN901 is a CD56-targeting antibody-drug conjugate designed for tumor-selective delivery of the cytotoxic maytansinoid DM1. This phase 1 study investigated the safety, tolerability, pharmacokinetics, and preliminary activity of IMGN901 in patients with CD56-expressing solid tumors. Methods Patients were enrolled in cohorts of escalating IMGN901 doses, administered intravenously, on 3 consecutive days every 21 days.

Comprehensive biomarker analysis and final efficacy results of sorafenib in the BATTLE trial.

Purpose: To report the clinical efficacy of sorafenib and to evaluate biomarkers associated with sorafenib clinical benefit in the BATTLE (Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination) program.

Patients And Methods: Patients with previously treated non-small cell lung cancer (NSCLC) received sorafenib until progression or unacceptable toxicity. Eight-week disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were assessed.

Prognostic value of positron emission tomography/computed tomography findings in limited-stage small cell lung cancer before chemoradiation therapy.

Objectives: Positron emission tomography/computed tomography (PET/CT) is increasingly used for disease staging and evaluation of treatment effectiveness in limited-stage small cell lung cancer (LS-SCLC). However, the prognostic value of PET/CT metrics in LS-SCLC is not clear.

Methods: Subjects in this retrospective study were 50 patients with LS-SCLC who had had PET/CT before definitive chemoradiation therapy in January 2003 to August 2009; 15 (29%) had also had induction chemotherapy.