Survival in EGFR+ NSCLC Improves With Anlotinib/Icotinib

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Anlotinib (AL3818), a novel multi-targeting tyrosine kinase inhibitor, and icotinib, a first-generation EGFR TKI, demonstrated efficacy and tolerability in the first line for the treatment of patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC), according to findings from the phase 2 ALTER-L004 study (NCT03736837).¹

The findings, published in the Journal of Hematology & Oncology, showed a median progression-free survival (PFS) of 15.1 months (95% CI, 12.6-17.6) at a median follow-up of 26.9 months (range, 15.0-38.9), meeting the primary end point of the study. The median duration of response was 13.5 months (95% CI, 10.0-17.1), and the median overall survival (OS) was 30.0 months (95% CI, 25.5-34.5).

Moreover, anlotinib still showed PFS and OS improvements in patients with pathogenic concurrent mutations. The median PFS in this population was 15.6 months (95% CI, 12.5-18.7), and the median OS was not reached (NR; 95% CI, 17.46-NR).

“The ALTER-L004 trial was a multicenter, phase 2 single-arm exploratory clinical trial strongly suggesting the efficacy and safety of anlotinib combined with icotinib in patients with EGFR-mutated advanced NSCLC,” study authors wrote. The study authors note that patients with NSCLC harboring EGFR or other concurrent mutations typically have poor prognoses.

“According to the findings of this study, patients harboring pathogenic concurrent mutations are more suitable for the anlotinib [plus]icotinib regimen option,” the authors concluded.

A total of 60 patients were enrolled in the multicenter trial between December 2018 and November 2020. Thirty-one patients (52%) had concurrent mutations, and 29 patients (48%) had pathogenic concurrent mutations.

For safety, all patients experienced treatment-related adverse events (TRAEs). Grade 3 or higher TRAEs were observed in 26 patients (43.7%), and 1 patient (1.7%) had a serious TRAE. Twenty-three patients (38.3%) had dose interruptions, 15 patients (25.0%) reduced dose, and 5 patients (8.3%) discontinued treatment due to TRAEs.

The most common TRAEs were hypertriglyceridemia (65%), hypertension (57%), hypercholesterolemia (52%), proteinuria (50%), diarrhea (50%), hand-foot syndrome (35%), hypothyroidism (33%), elevated thyroid stimulating hormone (28%), rash (27%), increased alanine transaminase (25%), increased low-density lipoprotein (22%), elevated aspartate aminotransferase (20%), fecal occult blood (17%), bleeding gums (17%), oral mucositis (15%), urine occult blood (15%), and hematuria (15%).

For grade 3 or higher TRAEs, the most common were hypertension (25%) and diarrhea (5%). The grade 4 TRAE was hypertriglyceridemia.

“Our team is now conducting a multicenter, phase 3 [randomized] clinical trial in EGFR-mutant NSCLC patients with pathogenic concurrent mutations, comparing anlotinib combined with icotinib vs icotinib [NCT04797806]. It is expected that further analysis of patients harboring concurrent mutations will be further studied with the aim of achieving better outcomes,” the study authors wrote.

Similar PFS benefits have been seen with anlotinib in other cancer types. Anlotinib demonstrated a median PFS of 40.5 months vs 8.4 months with placebo in patients with differentiated thyroid carcinoma, according to findings from a phase 2 study published earlier this year.²

REFERENCES:

1. Zhang L, Wang L, Wang J, et al. Anlotinib plus icotinib as a potential treatment option for EGFR-mutated advanced non-squamous non-small cell lung cancer with concurrent mutations: final analysis of the prospective phase 2, multicenter ALTER-L004 study. Mol Cancer. 2023;22(1):124. Published 2023 Aug 5. doi:10.1186/s12943-023-01823-w

2. Chi Y, Zheng X, Zhang Y, et al. Anlotinib in locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma: A randomized, double-blind, multicenter phase II trial. Clin Cancer Res. 2023;29(20):4047-4056. doi:10.1158/1078-0432.CCR-22-3406