bims-meluca 2025-10-26 papers

BMC Cancer. 2025 Oct 21. 25(1): 1616

Combination of chemotherapy and immune checkpoint inhibitors in non-small cell lung cancer with actionable gene alterations other than EGFR, ALK, and ROS1 mutations: a retrospective observational study.

Ji Eun Shin, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn.

BACKGROUND: Discoveries of actionable gene alterations (AGAs) have driven significant advances in targeted therapies, enhancing survival for non-small cell lung cancer (NSCLC) patients. In cases of AGAs other than common EGFR, ALK, and ROS1 mutations, target therapies have various strengths of the recommendation depending on their previous studies. Meanwhile, the immune checkpoint inhibitors (ICIs) combined with chemotherapy is still widely used as a first-line treatment for most of NSCLC with AGAs due to limited accessibility of target therapy.
METHODS: This study included patients with NSCLC harboring AGAs who received chemotherapy plus ICIs (CT + IO) or chemotherapy alone (CT) as a first-line treatment between January 2019 and May 2023 at Samsung Medical Center. We assessed the objective response rate (ORR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) between treatment groups. Subgroup analyses were conducted in the CT + IO group according to the type of AGAs and PD-L1 expression.
RESULTS: In total, 163 NSCLC patients with AGAs other than common EGFR, ALK, and ROS1 were included, with a median age of 62.4 years. 57 (35.0%) patients received CT + IO and 106 (65.0%) received CT. The proportions of patients with EGFR exon 20 insertion (E20I), HER2 mutation (mHER2), RET fusion (RET), and MET exon 14 skipping (METex14) were 28.8% (n = 47), 39.9% (n = 65), 16.6% (n = 27), and 14.7% (n = 24), respectively. With 32.0 months of median follow-up duration (range: 28.5-37.0), median PFS was 8.0 months (95% CI, 6.0-12.8) in CT + IO and 6.4 months (95% CI, 5.5-8.0) in CT (HR: 0.71, 95% CI, 0.49-1.03). In CT + IO group, median PFS by AGAs were 5.0 months (95% CI, 3.2-NA), 8.3 months (95% CI, 6.0-NA), 5.8 months (95% CI, 4.5-NA), and 17.1 months (95% CI, 10.7-NA) for E20I, mHER2, RET and METex14 respectively. Among these, 44.4% of METex14 patients had a PD-L1 TPS of 50% or higher. 24-month OS rate according to PD-L1 expression were 45.4%, 56.3%, and 81.5% in PD-L1 TPS < 1%, 1 to 49%, and ≥ 50%.
CONCLUSIONS: The combination of chemotherapy with ICIs in NSCLC patients with AGAs other than common EGFR, ALK, and ROS1 mutations demonstrated similar clinical outcomes compared to conventional chemotherapy. Patients with METex14 were associated with higher response rate and longer PFS among patients with AGAs when treated with chemotherapy plus ICIs. Also, the efficacy of the chemotherapy plus ICIs is positively correlate to the PD-L1 expression.

Keywords: Actionable gene alterations (AGAs); Chemo-immunotherapy; EGFR exon 20 insertion; HER2 mutation; Immune checkpoint inhibitors (ICIs); MET exon 14 skipping; Non-small cell lung cancer (NSCLC); RET rearrangement

DOI: https://doi.org/10.1186/s12885-025-14834-1

Biochem Pharmacol. 2025 Oct 21. pii: S0006-2952(25)00710-5. [Epub ahead of print]242(Pt 4): 117445

PTGFRN promotes non-small cell lung cancer malignant progression and reprograms BCAA metabolism by activating STAT3/BCAT1 pathway.

Feiye Liu, Mengjie Li, Peng Yu, Chuanchun Han, Lili Tian, Dachuan Shen, Jing Song.

Prostaglandin F2 receptor negative regulator (PTGFRN) is a transmembrane protein that has been linked to the metastatic behavior of certain cancers. However, its specific function and underlying regulatory mechanisms in lung cancer remain unclear. In this research, we observed that PTGFRN expression was markedly increased in lung cancer tissues compared to normal tissues, and patients with high PTGFRN levels exhibited poorer survival outcomes. Silencing PTGFRN significantly inhibited non-small cell lung cancer cell proliferation, tumor formation, and metastatic capacity. Mechanistically, PTGFRN was found to interact with signal transducer and activator of transcription 3 (STAT3)and inhibit its degradation. The resulting accumulation of STAT3 enhanced its binding to the BCAT1 gene promoter, thereby boosting branched-chain amino acid transaminase 1 (BCAT1) expression. This subsequently elevated branched-chain amino acid (BCAA) metabolism in lung cancer cells. Overall, our findings highlight the tumor-promoting role of PTGFRN in non-small cell lung cancer and demonstrate that PTGFRN accelerates cancer progression by enhancing the STAT3/BCAT1 signaling axis and reprogramming BCAA metabolism.

Keywords: BCAA metabolism; Non-small cell lung cancer; PTGFRN; STAT3

DOI: https://doi.org/10.1016/j.bcp.2025.117445

Ann Oncol. 2025 Oct 17. pii: S0923-7534(25)04788-X. [Epub ahead of print]

Alectinib versus crizotinib in previously untreated ALK-positive advanced non-small cell lung cancer: final overall survival analysis of the phase III ALEX study.

BACKGROUND: ALEX, a global, randomized, phase III trial evaluated alectinib versus crizotinib in patients with advanced ALK-positive non-small cell lung cancer (NSCLC). This final analysis provides mature overall survival (OS), duration of response (DOR) and long-term safety data.
PATIENTS AND METHODS: Treatment-naïve patients with stage III/IV ALK-positive NSCLC were randomly assigned to receive alectinib [600 mg twice daily (b.i.d.)] or crizotinib (250 mg b.i.d.) until disease progression, unacceptable toxicity, withdrawal, or death. Primary endpoint was investigator-assessed progression-free survival (previously reported). Key secondary endpoints included OS, DOR and safety.
RESULTS: A total of 303 patients (alectinib, n = 152; crizotinib, n = 151) were enrolled. At the updated data cut-off (28 April 2025), after a median follow-up of 53.5 (alectinib) and 23.3 (crizotinib) months, median OS was 81.1 [95% confidence interval (CI) 62.3 months-not estimable] versus 54.2 (95% CI 34.6-75.6 months) months, respectively [hazard ratio (HR) 0.78; 95% CI 0.56-1.08]. Improvement in median OS was observed with alectinib in patients with and without central nervous system (CNS) metastases at baseline [with CNS metastases: 63.4 (n = 59) versus 30.9 (n = 53) months with alectinib versus crizotinib, respectively (HR 0.68; 95% CI 0.40-1.15); without CNS metastases: 94.0 (n = 93) versus 69.8 (n = 98) months (HR 0.87; 95% CI 0.58-1.32)]. Median DOR in confirmed responders was longer with alectinib (42.3 months, 95% CI 31.3-51.3 months) versus crizotinib [11.1 months, 95% CI 7.9-13.0 months (HR 0.41; 95% CI 0.30-0.56)]. Long-term safety (median duration of alectinib treatment, 28.1 months) remained consistent with earlier reports, with no new or unexpected safety concerns identified.
CONCLUSIONS: These final OS data show the sustained long-term systemic and intracranial efficacy of alectinib in the first-line treatment of ALK-positive NSCLC and confirm alectinib as a standard of care in this setting.

Keywords: ALEX; alectinib; anaplastic lymphoma kinase; non-small cell lung cancer; overall survival

DOI: https://doi.org/10.1016/j.annonc.2025.09.018