SEARCH · PubMed Health

Results for “Pemetrexed”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

10 recordsLinked to original sources

PubMed2026

Prophylactic folinic acid prevents pemetrexed myelosuppression: A randomized trial toward safer treatment with chemotherapy in non-small cell lung cancer.

Background Pemetrexed is a cornerstone in advanced non-small cell lung cancer treatment. Although generally well tolerated, severe myelosuppression occurs in 26% of patients. Preventing chemotherapy-associated toxicity has become increasingly important with the introduction of osimertinib combined with pemetrexed-based chemotherapy. Due to substantial toxicity, this regimen is often not administered to frail patients. Folinic acid prophylaxis can mitigate pemetrexed-induced toxicity, however its preventive use has not been routinely studied. We aimed to investigate the efficacy of folinic acid prophylaxis to reduce myelosuppression. Methods Fifty patients treated with pemetrexed were randomized (1:1) to receive pemetrexed with or without oral folinic acid prophylaxis on days 2-4 after each chemotherapy cycle. The primary endpoint was absolute neutrophil count (ANC) after the first chemotherapy cycle. Secondary endpoints included ANC after the second cycle, grade neutropenia, treatment efficacy, renal function and incidence of dose modifications. Results Twenty-four patients received folinic acid and twenty-six served as controls. Higher ANC were observed in the folinic acid group after the first cycle (median 3.79; IQR 2.22-4.93 vs. 1.85; IQR 1.43-3.78; p.

Humans↗

PubMed2025

A Single-Arm Phase 2 Study of Sotorasib Plus Carboplatin and Pemetrexed in Patients With Advanced Nonsquamous NSCLC With KRAS G12C Mutation (WJOG14821L, SCARLET).

INTRODUCTION: The efficacy and safety of sotorasib plus platinum doublet chemotherapy in KRAS G12C-mutated nonsquamous NSCLC (nonsq NSCLC) have been previously reported with a limited follow-up period. METHODS: SCARLET is a single-arm phase 2 study involving chemotherapy-naive patients with KRAS G12C-mutated nonsq NSCLC. The participants received 960 mg daily plus four cycles of carboplatin (area under the curve = 5)/pemetrexed 500 mg/m2, followed by sotorasib/pemetrexed until disease progression. The primary end point was the overall response rate (ORR) and the secondary end points were progression-free survival (PFS), overall survival, and safety. Using plasma samples, next-generation sequencing was performed at baseline, 3 weeks, and during disease progression (the Japan Registry of Clinical Trials number 2051210086). RESULTS: Thirty patients were enrolled between October 2021 and July 2022 with a median follow-up of 14.8 months. ORR was 88.9% (80% confidence interval [CI]: 78.5%-94.8%, 95% CI: 70.8%-97.6%), median PFS was 6.6 months (95% CI: 5.3-16.7 mo), and median overall survival was 20.6 months (95% CI: 8.1 mo-not estimated). Among patients with programmed death-ligand 1 expression levels of 1% or higher and less than 1%, the ORRs were 82.3 and 100%, respectively, and the median PFS was 7.6 and 9.7 months, respectively. Using plasma samples, patients without KRAS G12C at baseline, without KRAS-related pathway co-alterations, or who cleared KRAS G12C at 3 weeks had better median PFS (16.7, 13.9, 8.7 mo, respectively). Tumor protein 53 mutations and EGFR and MET amplification were detected as acquired resistance. CONCLUSIONS: In patients with KRAS G12C-mutated nonsq NSCLC, sotorasib plus carboplatin/pemetrexed reported favorable efficacy, particularly for patients with less than 1% programmed death-ligand 1, with manageable toxicity.

Humans↗

PubMed2026

Osimertinib With or Without Chemotherapy in Advanced Non-Small Cell Lung Cancer With EGFR and Concurrent TP53 Mutations: A Randomized Clinical Trial.

IMPORTANCE: Combination therapy has emerged as a promising therapeutic approach for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, its clinical benefit-risk profile remains a focus of ongoing debate. Identifying patients most likely to derive benefit from such regimens remains an unmet clinical need. OBJECTIVE: To prospectively compare the efficacy and safety of first-line osimertinib plus chemotherapy with osimertinib monotherapy for patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, open-label, phase 3 study conducted at 17 sites in China. Between March 25, 2021, and July 11, 2024, a total of 294 eligible patients with treatment-naive, stage IV or recurrent nonsquamous NSCLC harboring concurrent TP53 and EGFR-sensitizing mutations were enrolled. INTERVENTIONS: Patients were randomized (1:1) to receive osimertinib plus chemotherapy (pemetrexed and carboplatin every 3 weeks for 4 cycles, followed by maintenance therapy of osimertinib plus pemetrexed; n = 146) or osimertinib monotherapy (n = 148). MAIN OUTCOMES AND MEASURES: The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, response, safety, and quality of life. RESULTS: Among 294 enrolled patients, the median age was 57 years (range, 26-79 years), and 159 (54.1%) were female. The data cutoff date was November 11, 2025. At a median follow-up of 25.1 months for the osimertinib-chemotherapy group and 26.1 months for the osimertinib monotherapy group, median progression-free survival was significantly longer with osimertinib plus chemotherapy than with osimertinib monotherapy (34.0 vs 15.6 months; difference, 18.4 months [95% CI, 9.9-22.3]; hazard ratio, 0.44 [95% CI, 0.32-0.60]; P < .001). This benefit was consistent across prespecified subgroups, including those with brain metastases and L858R mutations. The overall survival data remained immature (30.6% maturity); however, a trend toward overall survival benefit with combination therapy was observed. The incidence of grade 3 or higher treatment-related adverse events was higher in the combination group, with no new safety signal identified. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, osimertinib plus chemotherapy significantly increased progression-free survival among patients with EGFR-mutated advanced NSCLC harboring concurrent TP53 mutations. These findings provided a clinical rationale for individualized combination strategies in the management of patients with EGFR-mutated NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04695925.

Adult↗

PubMed2025

Clinicopathologic and genomic analyses of SMARCA4-mutated non-small cell lung carcinoma implicate the needs for tailored treatment strategies.

BACKGROUND: The clinicopathologic and therapeutic significance of SMARCA4 mutation in non-small cell lung carcinoma (NSCLC) remains unclear. METHODS: We retrieved 575 NSCLC cases from the clinical target sequencing cohort (N = 2157) to compare the clinicopathologic characteristics of groups subclassified based on the presence of truncated or non-truncated SMARCA4 mutations (SMARCA4-truncated, SMARCA4-non-truncated, and SMARCA4-wild type [WT]). The differences in gene expression profiles between these groups were evaluated using the TCGA-LUAD dataset. RESULTS: Fifty (2.3%) SMARCA4-truncated and 63 (2.9%) SMARCA4-non-truncated NSCLCs were identified. The majority of SMARCA4-truncated NSCLCs were present in male smokers (94.0%) and pathologically diagnosed as adenocarcinoma (76.0%). The SMARCA4-truncated group showed rare targetable driver alterations with a higher tumor mutation burden than the SMARCA4-WT group. Gene expression profile analysis revealed that cancer/testis antigen (CTA) expression was enriched in the SMARCA4-truncated group, with up to 57% of the cases displaying immunoreactivities for MAGEA4, CT45A, and/or PRAME. The SMARCA4-non-truncated group showed heterogeneous clinicopathologic, genomic, and immunohistochemical features that fell between SMARCA4-truncated and WT groups. Both SMARCA4-truncated and non-truncated groups showed significantly poor prognosis with pemetrexed-platinum chemotherapy, yet there was no significant difference in survival following immune checkpoint inhibitor monotherapy. CONCLUSION: SMARCA4-truncated NSCLC represents a variant of driver-negative NSCLC, mainly occurring in male smokers with poorly differentiated adenocarcinoma histology. In contrast, SMARCA4-non-truncated NSCLC indicates a heterogeneous subpopulation, exhibiting intermediate characteristics between the SMARCA4-truncated and SMARCA4-WT groups. While showing poor response to pemetrexed-platinum chemotherapy, increased CTA expression could be a novel therapeutic target in SMARCA4-mutated NSCLCs.

Humans↗

PubMed2025

Real-world frontline treatments in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor exon 20 insertions and adjusted comparisons versus amivantamab plus chemotherapy from the PAPILLON study.

INTRODUCTION: In PAPILLON, frontline amivantamab + carboplatin + pemetrexed (ACP) demonstrated superior efficacy over carboplatin + pemetrexed in patients with advanced or metastatic non-small-cell lung cancer (aNSCLC) harboring mutations in epidermal growth factor receptor (EGFR) exon 20 insertions (exon20ins). Real-world (RW) treatment patterns and comparative effectiveness of ACP versus RW treatments are unknown. MATERIALS AND METHODS: The present study (NECTAR) retrospectively analyzed frontline treatments prescribed 2012-2023 for patients with aNSCLC and confirmed EGFR exon20ins from English (ENG-NCRD), French (FR-ESME), and US (US-COTA and US-ConcertAI) datasets. Overall survival (OS), time to next treatment (TTNT), and progression-free survival (PFS) were assessed in RW pooled and individual treatment classes and in indirect treatment comparisons (ITC) between ACP from PAPILLON and RW treatments using Cox proportional hazards model adjusted for prognostic factors. RESULTS: NECTAR assessed 208 RW patients: ENG-NCRD, n = 23; FR-ESME, n = 91; US-COTA, n = 39, and US-ConcertAI, n = 55. Common frontline treatment classes were platinum-based chemotherapy (33.7 %), platinum + immunotherapy (23.1 %), EGFR tyrosine kinase inhibitors (TKIs) alone (15.4 %), platinum + VEGF inhibitors (VEGFi) (11.1 %), and immunotherapy alone (7.7 %). Compared with platinum-based chemotherapy, none of the evaluated treatment classes demonstrated improved OS, TTNT, and PFS. Exceptions were platinum + VEGFi in TTNT and PFS and platinum + immunotherapy in TTNT. In ITCs, ACP significantly improved OS over pooled RW treatments (HR = 0.48 [95 % CI, 0.32-0.71]; P < 0.001), platinum-based chemotherapy (HR = 0.48 [0.30-0.77]; P = 0.003), platinum + immunotherapy (HR = 0.41 [0.23-0.73]; P = 0.003), and EGFR TKI alone (HR = 0.48 [0.23-1.02]; P = 0.055). TTNT and PFS results were similar to OS. CONCLUSIONS: In patients with EGFR exon20ins aNSCLC, frontline ACP was superior to common RW treatments, highlighting the need for practice change.

Humans↗

PubMed2026

DESTINY-Lung06: trastuzumab deruxtecan and pembrolizumab as first-line treatment for HER2-overexpressing, PD-L1 TPS <50% NSCLC.

Non-small cell lung cancer (NSCLC) that overexpresses human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis, and no HER2-targeting therapies for HER2-overexpressing NSCLC are currently approved in the first-line setting. Pembrolizumab plus pemetrexed and platinum-based chemotherapy is a recommended first-line treatment option for nonsquamous NSCLC with no actionable genomic alterations. However, improved outcomes with pembrolizumab-based therapies correlate with higher programmed death-ligand 1 (PD-L1) levels, underscoring the need for more targeted treatment options for patients with lower PD-L1 tumor proportion scores (TPS; <50%). DESTINY-Lung06 is a multicenter, open-label, randomized, phase III trial evaluating the efficacy and safety of trastuzumab deruxtecan (T-DXd) in combination with pembrolizumab in the first-line setting in patients with HER2-overexpressing (≥25% moderate/strong membrane staining), PD-L1 TPS <50% NSCLC. Planned enrollment will be approximately 686 patients randomly assigned to either T-DXd 5.4 mg/kg with pembrolizumab 200 mg intravenously every 3 weeks (Q3W) or pembrolizumab 200 mg plus pemetrexed 500 mg/m2 with platinum-based chemotherapy (cisplatin 75 mg/m2 or carboplatin under the concentration-time curve 5 mg min/mL) intravenously Q3W. Progression-free survival by blinded independent central review and overall survival are the primary and key secondary endpoints of the study, respectively.Clinical trial registration: www.ClinicalTrials.gov identifier is NCT06899126; EudraCT identifier is 2024-515658-26-00.

First-line↗

PubMed2026

Serial CSF CA19-9 monitoring and CSF genomic profiling in ERBB2-mutant lung adenocarcinoma with leptomeningeal metastasis: a case report.

Leptomeningeal metastasis (LM) from ERBB2-mutant lung adenocarcinoma is difficult to treat and monitor because systemic disease and leptomeningeal disease may evolve discordantly. Evidence regarding cerebrospinal fluid (CSF) genomic profiling and serial CSF tumor marker monitoring in ERBB2-mutant non-small cell lung cancer with LM remains limited. We report a 48-year-old woman initially diagnosed with stage IB mucinous lung adenocarcinoma harboring an ERBB2 exon 20 p.G776delinsVC mutation. After surgery and adjuvant chemotherapy, she developed nodal recurrence and later presented with lower back pain and lower-limb numbness. LM was clinically diagnosed based on neurological symptoms, magnetic resonance imaging and CSF cytopathology. She received craniospinal irradiation, systemic therapy and subsequent intrathecal treatment. At month 33, CSF CA19-9 was markedly elevated despite no clear radiographic systemic progression. CSF next-generation sequencing(NGS) detected the same ERBB2 exon 20 p.G776delinsVC mutation as the primary lung tumor, with a higher variant allele fraction in CSF than in lung tissue.The patient subsequently received trastuzumab deruxtecan and sequential intrathecal therapy with pemetrexed, etoposide, cytarabine and pemetrexed rechallenge. Intrathecal treatment was adjusted according to serial CSF CA19-9 levels, neurological status, imaging findings, systemic disease activity and treatment-related toxicities. CSF CA19-9 was not used as a stand-alone criterion for progression or treatment modification.At the latest follow-up, she remained alive more than 36 months after the clinical diagnosis of LM. This case suggests that CSF NGS and serial CSF CA19-9 may provide further insights into disease activity within the integrated assessment of systemic and leptomeningeal disease. Their clinical applicability is still under investigation and necessitates future validation.

CA19-9↗

PubMed2026

Ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated non-small-cell lung cancer after disease progression on EGFR tyrosine kinase inhibitor therapy (HARMONi): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: Ivonescimab has shown clinical efficacy in non-small-cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated NSCLC whose disease progressed after third-generation EGFR tyrosine kinase inhibitor (TKI) therapy. METHODS: HARMONi is a randomised, placebo-controlled, double-blind, phase 3 trial done at 114 cancer centres and hospitals across Asia, Europe, and North America. Eligible patients were aged at least 18 years (upper limit: 75 years in Asia) with stage IIIB/IIIC or IV non-squamous EGFR-mutated NSCLC, disease progression after treatment with a third-generation EGFR-TKI, and an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) via a centralised interactive voice response system or interactive web response system to receive ivonescimab (20 mg/kg) or placebo plus pemetrexed (500 mg/m2) and carboplatin (target area under the curve 5 mg/mL per min) intravenously every 3 weeks. Randomisation was stratified by brain metastases status at enrolment and geographical region. The primary endpoints were progression-free survival by blinded independent radiology review committee and overall survival in the intention-to-treat population. Safety was assessed in patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov (NCT06396065), has completed enrolment, and is ongoing for treatment and follow-up. FINDINGS: From Jan 25, 2022, to Oct 1, 2024, 660 individuals were screened for eligibility; of these, 438 were enrolled and randomly assigned to receive ivonescimab plus chemotherapy or placebo plus chemotherapy (219 per group). Of enrolled patients, 257 (59%) were female and 181 (41%) were male; 306 (70%) reported race as Asian, and 105 (24%) as White. At a median follow-up of 22·3 months (95% CI 21·5-23·0), 275 progression or death events had occurred in 345 patients (129 events among 172 patients in the ivonescimab plus chemotherapy group and 146 events among 173 patients in the placebo plus chemotherapy group). Median progression-free survival was 6·8 months (95% CI 5·7-7·1) in the ivonescimab plus chemotherapy group versus 4·4 months (4·1-5·5) in the placebo plus chemotherapy group (hazard ratio [HR] 0·52; 95% CI 0·41-0·66; p<0·0001). At a median follow-up of 29·7 months (95% CI 27·7-31·0), 262 deaths occurred in 438 patients (122 in the ivonescimab plus chemotherapy group and 140 in the placebo plus chemotherapy group). Median overall survival was 16·8 months (14·3-19·0) in the ivonescimab plus chemotherapy group versus 14·0 months (12·8-15·7) in the placebo plus chemotherapy group (HR 0·79; 0·62-1·01). The most common grade 3-4 treatment-related adverse events in the ivonescimab plus chemotherapy versus the placebo plus chemotherapy group were decreased neutrophil count (42 [19%] of 218 vs 36 [17%] of 218), decreased white blood cell count (28 [13%] vs 24 [11%]), decreased platelet count (27 [12%] vs 14 [6%]), and anaemia (22 [10%] vs 27 [12%]). Serious treatment-related adverse events occurred in 61 (28%) patients in the ivonescimab plus chemotherapy group and 33 (15%) patients in the placebo plus chemotherapy group. Treatment-related adverse events led to death in four patients (disease progression, multiple organ dysfunction syndrome, and hepatic failure, each in one patient; gastrointestinal haemorrhage and pulmonary embolism in one patient) in the ivonescimab plus chemotherapy group and five patients (pneumonitis, myocardial infarction, cerebrovascular accident, cognitive disorder, and embolic stroke, each in one patient) in the placebo plus chemotherapy group. INTERPRETATION: Ivonescimab plus chemotherapy showed a clinically meaningful and statistically significant progression-free survival benefit in patients with EGFR-mutated NSCLC after progression on EGFR-TKI therapy. The clinical benefit and lack of new safety signals of ivonescimab with chemotherapy support the potential for the combination as a new treatment option in this patient population. FUNDING: Summit Therapeutics.

Humans↗

PubMed2026

Clinical pharmacokinetics of afatinib: A systematic review.

BACKGROUND: Afatinib is commonly used in the treatment of non-small cell lung cancer (NSCLC). This systematic review summarizes clinical pharmacokinetics (PK) evidence focusing on the effect of disease state and drug interactions on afatinib exposure. METHODS: Google Scholar, Science Direct, PubMed, and the Cochrane library were searched for human studies reporting the clinical PK of afatinib. The search yielded 24 articles that met the predefined inclusion criteria. RESULTS: Afatinib exposure increased slightly more than dose proportionally, with higher doses producing greater AUC0-24 and Cmax values. The apparent oral clearance reported after administration of the oral solution was lower than that observed following tablet administration. The Cmax of afatinib increases by 38.5% after coadministration with ritonavir and exposure decreases 34.3% with rifampicin. The Cmax decreases 31.45% when given with pemetrexed. Both the AUC0-24 and Cmax increase in NSCLC and tumor state. The AUC0-24 of afatinib is 2.61 folds higher following multiple oral doses among patients with solid tumors. Afatinib exposure is 22.1 % higher in renal impaired patients than in healthy controls. In grade 2 diarrhea, the AUC0-24 of afatinib is 83.93% higher as than in grade 0-1 diarrhea in solid tumor patients. CONCLUSION: This systematic review provides an updated synthesis of clinical PK evidence on afatinib. Afatinib exposure is influenced by dose, repeated administration, renal impairment, diarrhea associated toxicity, and P-glycoprotein mediated drug interactions. These findings may support individualized dosing, toxicity-guided dose adjustment, and future development of PK models for afatinib.

Humans↗

PubMed2025

Artificial intelligence-powered spatial analysis of tumor microenvironment in patients with non-small cell lung cancer with acquired resistance to EGFR tyrosine kinase inhibitor.

PURPOSE: This study evaluated the dynamic changes in the tumor microenvironment (TME) in patients with non-small cell lung cancer (NSCLC) and acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) using an artificial intelligence (AI)-powered spatial TME analyzer. We then assessed the predictive efficacy of immune-checkpoint inhibitors (ICIs)-based treatment. EXPERIMENTAL DESIGN: An AI-powered whole-slide image analyzer was used to segment cancer areas (CAs) and cancer stroma and to identify tumor-infiltrating lymphocytes (TILs), tertiary lymphoid structures, fibroblasts, and endothelial cells (ECs) in the tumor tissue. We analyzed 143 NSCLC samples after resistance to EGFR-TKIs from two cohorts: (1) 89 patients treated with ICI monotherapy and (2) 54 patients from the ATTLAS phase III trial comparing atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP) versus pemetrexed plus carboplatin. RESULTS: Post-TKI samples showed reduced TILs in the CA (p=0.045) and increased ECs in the CA (p=0.005) compared with pre-TKI samples. These changes differed according to EGFR mutation subtype. Higher TILs in CA were associated with a better overall response rate (ORR) and progression-free survival (PFS). Similarly, higher EC levels in CA correlated with improved ORR and PFS. In the ATTLAS cohort, these factors were associated with clinical benefits from ABCP, with a significant association with TILs and a marginal association with ECs. CONCLUSION: Our findings suggest that EGFR-TKIs affect the immune landscape of patients with EGFR-mutated NSCLC. Higher TILs or ECs in the CA were significantly associated with a favorable response to subsequent ICI-based treatment. TRIAL REGISTRATION NUMBER: NCT03991403.

Aged↗