RET-AREAL: A multi-center, real-world data analysis on the efficacy of pralsetinib in acquired RET fusion after resistance to EGFR/ALK-TKIs.

Pralsetinib demonstrated impressive improvement of survival in non-small cell lung cancer (NSCLC) patients harbored de novo RET fusion. However, the efficacy in patients with acquired RET fusion after resistance to EGFR/ALK-TKIs has only been reported on a case-by-case basis, and the strategy for overcoming the acquired RET fusion has not been fully investigated. This multicenter, real-world analysis enrolled 32 patients with unresectable NSCLC harbored acquired RET fusion after resistance to EGFR/ALK-TKIs in 23 centers across China from July 1st, 2018 to Nov 23rd, 2022. Epidemiological, clinical, genetic, and treatment data were collected. The primary outcome was time to treatment failure (TTF). Secondary outcomes were overall survival (OS), objective response rate (ORR), disease control rate (DCR) and toxicity. In real-world context, patients underwent pralsetinib-based treatment had a higher proportion of central nervous system metastasis. EGFR 19del was the predominant mutation type (62.5 %) prior to acquired RET fusion. CCDC6 was the commonest RET fusion partner (40.6 %). "Clonal RET fusion" (c-RET) and "subclonal RET fusion" (s-RET) were defined according to the RET fusion allele frequency. Patients with c-RET had higher proportions of undetected EGFR mutation and KIF5B-RET fusion. First-line pralsetinib-based therapy had notably superior median TTF when compared to their counterparts (8.03 versus 4.30 months, P = 0.016). Notably, patients with c-RET had a better prognosis than those with s-RET (median TTF: NR versus 5.67 months, P = 0.037, median OS: NR versus 9.83 months, P = 0.047). In conclusion, pralsetinib-based therapy may be a potential strategy to overcome acquired RET fusion after resistance to EGFR/ALK-TKIs.

Tang X ，Hu J ，Guo R ，Wang Y ，Yao Y ，Zeng L ，Wang H ，Shen H ，Chen J ，Huang W ，Liu L ，Su M ，Yu Z ，Mao W ，Wang J ，Tao H ，Dong G ，Cai C ，Xie Y ，Qu T ，Zhang Y ，Shen W ，Cao J ，Cai X ，Kong W ，Li X ，Liang F ... -  《-》

Pralsetinib in patients with RET fusion-positive non-small-cell lung cancer: A plain language summary of the ARROW study.

Griesinger F ，Curigliano G ，Subbiah V ，Baik CS ，Tan DS ，Lee DH ，Misch D ，Garralda E ，Kim DW ，van der Wekken AJ ，Gainor JF ，Paz-Ares L ，Liu SV ，Kalemkerian GP ，Bowles DW ，Mansfield AS ，Lin JJ ，Smoljanovic V ，Rahman A ，Zalutskaya A ，Louie-Gao M ，Boral AL ，Mazières J ... -  《-》

Real-world data of dacomitinib as first-line treatment for patients with EGFR-mutant non-small-cell lung cancer.

Dacomitinib demonstrated superior survival benefit compared to gefitinib as a first-line treatment in non-small cell lung cancer (NSCLC) patients with common EGFR mutations through ARCHER 1050. However, there is limited real-world data concerning its efficacy and safety. This study included patients with EGFR-mutant NSCLC who received dacomitinib as a first-line treatment between January 2021 and December 2022 at Samsung Medical Center and St. Vincent's Hospital. This study assessed the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), safety profile of dacomitinib, and subsequent treatments after dacomitinib failure. In total, 153 patients were included in this study. Exon 19 deletion was observed in 50.3% of patients, while the L858R mutation in exon 21 was observed in 46.4% of patients. 45.1% of patients had brain metastasis. The ORR was 84.3%. The median follow-up duration was 16.9 months, with a median PFS of 16.7 months (95% CI, 14.4 to 25.2). Based on the type of EGFR mutation, the median PFS was 18.1 months (95% CI, 14.5 to NE) in patients with exon 19 deletion, and 15.9 months (95% CI, 12.5 to NE) in patients with L858R mutation. Grade 3 or higher adverse events were observed in 7.2% of patients. Initially administered at a dose of 45 mg, dose reduction was necessary for 85.6% of patients, with a final dosage of 30 mg in 49.0% and 15 mg in 36.6% of cases. Out of the 60 patients who experienced disease progression, 31 underwent tissue re-biopsy and 25 underwent liquid biopsy. Overall, T790M mutation was detected in 40.9% of patients who progressed after dacomitinib. The survival benefit of dacomitinib has been demonstrated, indicating its promising efficacy in a real-world setting. The detection rate of the T790M mutation after dacomitinib treatment failure was comparable to that of other second-generation EGFR-TKIs.

Shin JE ，Jung HA ，Park S ，Sun JM ，Lee SH ，Ahn JS ，Ahn MJ ，Shim BY ... -  《Scientific Reports》

Efficacy and Tolerance of First-Line Afatinib in Elderly NSCLC Patients with EGFR Mutations in Vietnam: A Multicenter Real-World Study.

Do TA ，Nguyen HTT ，Pham PC ，Nguyen KT ，Hoang TTA ，Le AT ，Vuong HDT ，Nguyen TDN ，Dang KV ，Nguyen OT ，Pham LV ，Nguyen HM ，Vo TTH ，Kien DH ，Vu TH ，Nguyen HTT ，Pham TV ，Trinh HL ，Nguyen GH ，Truong MC ，Pham CTM ，Nguyen PTB ... -  《-》

Effects of EGFR-TKIs combined with intracranial radiotherapy in EGFR-mutant non-small cell lung cancer patients with brain metastases: a retrospective multi-institutional analysis.

Patients with non-small cell lung cancer (NSCLC) are prone to developing brain metastases (BMs), particularly those with epidermal growth factor receptor (EGFR) mutations. In clinical practice, treatment-naïve EGFR-mutant NSCLC patients with asymptomatic BMs tend to choose EGFR-tyrosine kinase inhibitors (TKIs) as first-line therapy and defer intracranial radiotherapy (RT). However, the effectiveness of upfront intracranial RT remains unclear. This was a retrospective study including 217 patients from two institutions between January 2018 and December 2022. Clinical data of NSCLC patients with BMs who received EGFR-TKIs were collected. The patients were assigned to one of the three groups according to the therapeutic modality used: the upfront TKI + stereotactic radiosurgery (SRS) / fractionated stereotactic radiotherapy (fSRS) group (upfront TKI + SRS/fSRS ), the upfront TKI + whole-brain radiotherapy (WBRT) group (upfront TKI + WBRT) and the upfront TKI group. As of March 8, 2023, the median follow-up duration was 37.3 months (95% CI, 32.5-42.1). The median overall survival (OS) for the upfront TKI + SRS/fSRS, upfront TKI + WBRT, and upfront TKI groups were 37.8, 20.7, and 24.1 months, respectively (p = 0.015). In subgroup analysis, the upfront TKI + SRS/fSRS group demonstrated longer OS compared to the upfront TKI + WBRT and upfront TKI groups in patients treated with first or second-generation EGFR-TKIs (p = 0.021) and patients with L858R mutation (p = 0.017), whereas no survival benefit was observed in three-generation EGFR-TKIs or 19del subgroup. In the multivariable analysis, metachronous BMs, EGFR L858R mutation and nonclassic EGFR mutation were identified as independent risk factors for OS, while a DS-GPA score of 2.0-4.0 was the only independent protective factor. This study demonstrated that upfront addition of SRS/fSRS to EGFR-TKIs was associated with longer OS compared to upfront WBRT or upfront TKI alone in EGFR-mutant NSCLC patients with BMs. This improvement was more significant in patients with L858R mutation and those treated with first or second-generation EGFR-TKIs. Further research with a larger sample size is warranted.

He M ，Wu X ，Li L ，Yi G ，Wang Y ，He H ，Ye Y ，Zhou R ，Xu Z ，Yang Z ... -  《Radiation Oncology》