Real-World Efficacy and Safety of Amivantamab for EGFR-Mutant NSCLC.

Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced NSCLC with EGFR exon 20 insertion mutations, after prior therapy. Nevertheless, the benefits and safety of amivantamab in other EGFR-mutant lung cancer, with or without osimertinib, and with concurrent radiation therapy, are less known. We queried the MD Anderson Lung Cancer GEMINI, Fred Hutchinson Cancer Research Center, University of California Davis Comprehensive Cancer Center, and Stanford Cancer Center's database for patients with EGFR-mutant NSCLC treated with amivantamab, not on a clinical trial. The data analyzed included initial response, duration of treatment, and concomitant radiation safety in overall population and prespecified subgroups. A total of 61 patients received amivantamab. Median age was 65 (31-81) years old; 72.1% were female; and 77% were patients with never smoking history. Median number of prior lines of therapies was four. On the basis of tumor's EGFR mutation, 39 patients were in the classical mutation cohort, 15 patients in the exon 20 cohort, and seven patients in the atypical cohort. There were 37 patients (58.7%) who received amivantamab concomitantly with osimertinib and 25 patients (39.1%) who received concomitant radiation. Furthermore, 54 patients were assessable for response in the overall population; 19 patients (45.2%) had clinical response and disease control rate (DCR) was 64.3%. In the classical mutation cohort of the 33 assessable patients, 12 (36.4%) had clinical response and DCR was 48.5%. In the atypical mutation cohort, six of the seven patients (85.7%) had clinical response and DCR was 100%. Of the 13 assessable patients in the exon 20 cohort, five patients (35.7%) had clinical response and DCR was 64.3%. Adverse events reported with amivantamab use were similar as previously described in product labeling. No additional toxicities were noted when amivantamab was given with radiation with or without osimertinib. Our real-world multicenter analysis revealed that amivantamab is a potentially effective treatment option for patients with EGFR mutations outside of exon 20 insertion mutations. The combination of osimertinib with amivantamab is safe and feasible. Radiation therapy also seems safe when administered sequentially or concurrently with amivantamab.

Wang K ，Du R ，Myall NJ ，Lewis WE ，Uy N ，Hong L ，Skoulidis F ，Byers LA ，Tsao A ，Cascone T ，Pozadzides J ，Tu J ，Negrao MV ，Gibbons DL ，Park K ，Rinsurongkawong W ，Lee JJ ，Gandara D ，Behl D ，Shu CA ，Riess JW ，Baik C ，Wakelee HA ，Vaporciyan AA ，Heymach JV ，Zhang J ，Le X ... -  《-》

The efficacy of continuing osimertinib with platinum pemetrexed chemotherapy upon progression in patients with metastatic non-small cell lung cancer harboring sensitizing EGFR mutations.

For patients with EGFR mutant NSCLC who progress on osimertinib, the clinical benefit of continuing osimertinib with next line platinum pemetrexed chemotherapy remains unknown. In this international, multi-center, retrospective cohort study, a total of 159 patients with EGFR mutant NSCLC who progressed on osimertinib and received platinum-pemetrexed therapy on progression from 2013 to 2023 were included. The data cutoff was December 31, 2023. Data analysis was conducted from January 2024 to June 2024. The primary endpoints were progression free survival (PFS) and overall survival (OS), analyzed using Kaplan-Meier methods. Multivariable Cox regression adjusting for patient-specific and cancer-specific factors was performed. 421 patients with EGFR mutant NSCLC with progression on osimertinib were identified, of which159 patients who met pre-specified inclusion criteria were divided into two groups: Cohort 1 (osimertinib + platinum-pemetrexed) included 50 patients (median [IQR] age, 59 [30 - 83] years; 36 [72.0 %] female; 11 [22.4 %] Asian) and Cohort 2 (platinum-pemetrexed alone) included 109 patients (median [IQR] age, 54 [25 - 80] years; 62 [56.9 %] female; 74 [64.9 %] Asian). Most patients were never smokers (Cohort 1, 37 [74.0 %]; Cohort 2, 66 [60.6 %]). One third of patients had baseline brain metastases (Cohort 1, 19 [38.0 %]; Cohort 2, 36 [38.3 %]). Both cohorts had a median of two prior lines of anti-cancer therapy. The addition of bevacizumab or immune checkpoint inhibitors (ICI) to next-line platinum-pemetrexed chemotherapy was more common in Cohort 2 (bevacizumab use, 30.3 % vs 8.0 %, p = 0.002; ICI use, 33.0 % vs 2.0 %, p = 0.001). With a median duration of follow up of 30 months, there was a significant PFS benefit to continuing osimertinib with next line platinum pemetrexed chemotherapy (9.0 vs 4.5 months; HR 0.49, 95 % CI 0.32 - 0.74, p = 0.0032), also seen in subset analyses of patients who received first line osimertinib (n = 55, 11.0 vs 6.2 months; HR 0.41, 95 % CI 0.25 - 0.73, p = 0.002). Among patients with EGFR mutant NSCLC without brain metastases after progression on osimertinib, we found that continuing osimertinib with next line platinum pemetrexed significantly reduced the median time to CNS progression (n = 38; 7.0 vs 4.1 months; HR 0.47, 95 % CI 0.48 - 0.98, p = 0.01). After adjusted analysis, there was no significant OS difference between Cohorts 1 and 2 (19 months vs 13 months; HR 0.92, 95 % CI 0.60 - 1.39, p = 0.68). For patients with EGFR mutant NSCLC who progress on osimertinib, there is a significant PFS, but not OS, benefit to continuing osimertinib with next line platinum pemetrexed chemotherapy. The continuation of osimertinib with next line platinum pemetrexed chemotherapy appears to reduce the risk of CNS progression.

Patil T ，Gao D ，Watson A ，Sakamoto M ，Nie Y ，Gibson A ，Dean ML ，Yoder BA ，Miller E ，Stalker M ，Aisner DL ，Bunn PA ，Schenk EL ，Marmarelis ME ，Bennati C ，Navani V ，Zhang Y ，Camidge DR ... -  《-》

Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC.

Amivantamab plus lazertinib (amivantamab-lazertinib) has shown clinically meaningful and durable antitumor activity in patients with previously untreated or osimertinib-pretreated EGFR (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). In a phase 3, international, randomized trial, we assigned, in a 2:2:1 ratio, patients with previously untreated EGFR-mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. Overall, 1074 patients underwent randomization (429 to amivantamab-lazertinib, 429 to osimertinib, and 216 to lazertinib). The median progression-free survival was significantly longer in the amivantamab-lazertinib group than in the osimertinib group (23.7 vs. 16.6 months; hazard ratio for disease progression or death, 0.70; 95% confidence interval [CI], 0.58 to 0.85; P<0.001). An objective response was observed in 86% of the patients (95% CI, 83 to 89) in the amivantamab-lazertinib group and in 85% of those (95% CI, 81 to 88) in the osimertinib group; among patients with a confirmed response (336 in the amivantamab-lazertinib group and 314 in the osimertinib group), the median response duration was 25.8 months (95% CI, 20.1 to could not be estimated) and 16.8 months (95% CI, 14.8 to 18.5), respectively. In a planned interim overall survival analysis of amivantamab-lazertinib as compared with osimertinib, the hazard ratio for death was 0.80 (95% CI, 0.61 to 1.05). Predominant adverse events were EGFR-related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).

Cho BC ，Lu S ，Felip E ，Spira AI ，Girard N ，Lee JS ，Lee SH ，Ostapenko Y ，Danchaivijitr P ，Liu B ，Alip A ，Korbenfeld E ，Mourão Dias J ，Besse B ，Lee KH ，Xiong H ，How SH ，Cheng Y ，Chang GC ，Yoshioka H ，Yang JC ，Thomas M ，Nguyen D ，Ou SI ，Mukhedkar S ，Prabhash K ，D'Arcangelo M ，Alatorre-Alexander J ，Vázquez Limón JC ，Alves S ，Stroyakovskiy D ，Peregudova M ，Şendur MAN ，Yazici O ，Califano R ，Gutiérrez Calderón V ，de Marinis F ，Passaro A ，Kim SW ，Gadgeel SM ，Xie J ，Sun T ，Martinez M ，Ennis M ，Fennema E ，Daksh M ，Millington D ，Leconte I ，Iwasawa R ，Lorenzini P ，Baig M ，Shah S ，Bauml JM ，Shreeve SM ，Sethi S ，Knoblauch RE ，Hayashi H ，MARIPOSA Investigators ... -  《-》

First-Line Osimertinib for Previously Untreated Patients With NSCLC and Uncommon EGFR Mutations: The UNICORN Phase 2 Nonrandomized Clinical Trial.

Okuma Y ，Kubota K ，Shimokawa M ，Hashimoto K ，Kawashima Y ，Sakamoto T ，Wakui H ，Murakami S ，Okishio K ，Hayashihara K ，Ohe Y ，Tokyo Cooperative Oncology Group (TCOG) ... -  《-》

Cardiac Events and Survival in Patients With EGFR-Mutant Non-Small Cell Lung Cancer Treated With Osimertinib.

Lin CY ，Chang WT ，Su PL ，Kuo CW ，Yang J ，Lin CC ，Lin SH ... -  《JAMA Network Open》