This case demonstrates unprecedented long-term survival in a patient with KRAS p.Q61H/TP53 c.G738A-mutant lung adenocarcinoma and brain metastasis treated with pemetrexed-based maintenance therapy combined with local interventions. The regimen showed efficacy, safety, and cost-effectiveness, offering a viable strategy for resource-limited settings.

Histology-based induction CRT followed by surgery demonstrated feasibility and favorable outcomes, particularly for Sq and EGFR-negative non-Sq NSCLC. These findings provide a reference for patients ineligible for immune checkpoint inhibitor-based therapy.

P2, N=17, Recruiting, West China Hospital | Not yet recruiting --> Recruiting | Trial completion date: Nov 2025 --> Jun 2026 | Trial primary completion date: Nov 2024 --> May 2026

P1/2, N=45, Active, not recruiting, Guangzhou Medical University | Trial primary completion date: Jan 2026 --> Jul 2026

To our knowledge, this is the first report to demonstrate the efficacy of carboplatin, pemetrexed, and amivantamab against LMD progression after osimertinib therapy, suggesting that this regimen may be a therapeutic option for patients with LMD, including those with symptomatic disease. Nevertheless, further studies are warranted to confirm efficacy in this population.

This study assessed clinical features and survival outcomes according to KRAS mutation in a real-life population of nsq-NSCLC patients treated with first-line platinum-pemetrexed-pembrolizumab.MethodsThis is a retrospective-prospective study including patients with nsq-NSCLC who received first-line platinum-pemetrexed-pembrolizumab from 4 September 2018 in 33 Italian Centers.ResultsAmong the 765 patients included in this analysis, 121 (15.8%) had KRAS p.G12C mutation, 201 (26.3%) KRAS non-p.G12C mutation and 443 (57.9%) KRAS WT. No difference in OS was found between KRAS p.G12C and KRAS non-p.G12C (15.9 vs 17.0 months, HR 0.93, 95% CI: 0.66-1.31, p=0.676).Median progression-free survival was significantly shorter in KRAS-mutated compared to KRAS WT patients (8.8 vs 10.8 months; adjusted HR 1.29, 95% CI 1.04-1.59, p=0.018), with no differences between KRAS p.G12C and KRAS non-p.G12C (8.8 vs 8.8 months, HR 0.95, 95% CI: 0.70-1.30, p=0.756).ConclusionsKRAS mutation showed a potential negative predictive role in advanced nsq-NSCLC treated with first-line chemo-immunotherapy. The impact of co-mutations and post-progression outcomes warrants further investigation.

The simulations indicated that OSI can start 48 h after PEM exposure (no extended drug holiday is needed) and that the PEM→OSI benefit remains robust across heterogeneity, including BIM-deletion polymorphisms and inter-individual variability in tumor drug sensitivity. This mechanism-based QSP-PK-PD framework connects whole-body PK to core PD processes, explains schedule-dependent synergy, and supports optimization of sequencing intervals and identification of likely responders.

The introduction of immune checkpoint inhibitors (anti-PD-1/PD-L1) has revolutionized first-line treatment, but second-line options remain largely dependent on older chemotherapies such as docetaxel or pemetrexed...Innovative strategies are under investigation: antibody-drug conjugates (anti-TROP-2, anti-CEACAM-5), cancer vaccines (TEDOPI), external electric fields (TTFields), oncolytic viruses, and PROTACs. While some of these show promise in progression-free survival, global survival benefit remains modest. The identification of robust predictive biomarkers is essential for tailoring future therapies.

P2, N=46, Not yet recruiting, Wake Forest University Health Sciences

The validation of the NMA results could be assessed for progression-free survival of selpercatinib versus pembrolizumab + pemetrexed + platinum-based chemotherapy. Enabling the earlier assessment of single-arm trials, via pseudo comparator arms, will provide payers with greater confidence in anticipated treatment effects. In light of the joint clinical assessment, incorporation of single-arm trials within NMA facilitates the reporting of predicted treatment effects relative to multiple relevant comparators, which is important when considering the use of interventions for the global market.

Following chemical exposure, epigenetic perturbations at the TK locus are detected by culturing cells under hypoxanthine-aminopterin-thymidine selection and quantifying the frequency of TK revertant colonies, which reflects restoration of TK gene expression...• By employing a DNA-methylated housekeeping TK gene and colony formation as the readout, the assay enables quantitative epigenetic changes without the need for specialized equipment. • The protocol offers a simple, quantitative, and cost-effective platform that is suitable for routine testing and comparative assessment of multiple compounds.

The absence of statistically significant survival difference and increased toxicity in the ICIs plus pemetrexed cohort suggest that chemotherapy may not be crucial in MT. Moreover, the significant benefits of ICIs-based therapy as a second-line treatment reinforce its value, offering confidence to both patients and physicians in making informed decisions regarding MT strategies and subsequent systemic therapies.