Study of anlotinib combined with icotinib as the first-line treatment in non-small cell lung cancer (NSCLC) patients harboring activating EGFR mutations (ALTER-L004).

Abstract

9573 Background: Anti-angiogenic monoclonal antibodies plus EGFR TKIs have previously shown to prolong PFS in patients with EGFR-mutated NSCLC (JO25567 and NEJ026). Unlike bevacizumab, anlotinib is more convenient with orally administered and can inhibit more targets. Monotherapy using anlotinib has significantly prolonged median PFS and OS compared with the placebo values for third-line treatment or beyond in advanced NSCLC. We conducted a study to investigate the activity of anlotinb combined with icotinib, an oral EGFR TKI. Methods: This is a prospective, single-arm, multicenter clinical trial. Patients with locally advanced and/or metastatic IIIB, IIIC or IV non-squamous NSCLC are enrolled. Patients with EGFR exon 19 deletion and/or exon 21 L858R mutation who have not received prior therapies are eligible. The regimen consists of anlotinib (12 mg p.o, qd, day 1 to 14 every 21-day cycle) and icotinib (125mg p.o, tid). The primary endpoint is PFS. Secondary endpoints are OS, ORR, DCR and safety. Results: Between Jul 2018 and Dec 2019, 35 patients were enrolled in five centers and treated with anlotinb and icotinib. At data cutoff (Jan 7, 2020), patients were followed up for a median of 6.01 months.32 tumors were analyzed with 30 evaluable. Preliminary efficacy results: ORR was 59% (0 CR, 19 PR), DCR was 88% (0 CR, 19 PR, 9 SD). 26 patients are still receiving treatment and the longest exposure was 14 cycles. 10 (67%) of 15 patients with exon 19 deletions and 9 (53%) of 17 patients with L858R mutations achieved an objective response. 18 patients harbored aberrations in additional oncogenic drivers (PIK3CA or AKT1) and/or tumor suppressors (TP53, RB1, and PTEN) with an ORR of 72%. Upon analyses, AEs were observed in 97% (34/35) of patients. No Gr 5 AEs were reported. The most common Grade 3 AEs were hypertension (6 [ 17% ]), hypertriglyceridemia (2 [6% ]), diarrhea (1 [ 3% ]), hyperuricemia (1 [ 3% ]), hand and foot skin reaction (1 [3%]), asthenia (1 [3%]), and acute coronary syndrome (1 [ 3% ]). Hypertriglyceridemia was the only grade 4 AE (2 [ 6% ]). Three patients had to adjust treatment dosage. Conclusions: The strategy of anlotinib plus icotinib showed encouraging efficacy for previously untreated, EGFR-mutated advanced NSCLC patients. The combination was well tolerated and the AEs were manageable. The follow-up time is not sufficient and the PFS and OS outcomes need further evaluation. Clinical trial information: NCT03736837 .