Dataset Information

Comparison of afatinib and erlotinib combined with bevacizumab in untreated stage IIIB/IV epidermal growth factor receptor-mutated lung adenocarcinoma patients: a multicenter clinical analysis study.

ABSTRACT:

Background

Although bevacizumab in combination with afatinib or erlotinib is an effective and safe first-line therapy for advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), there are very few clinical data comparing afatinib and erlotinib combined with bevacizumab. We performed a retrospective multicenter analysis for the comparison of two combination therapies.

Methods

Between May 2015 and October 2020, data of 135 stage IIIB/IV EGFR-mutated NSCLC patients receiving first-line afatinib or erlotinib combined with bevacizumab combination therapy in Linkou, Keelung, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals were retrieved and retrospectively analyzed.

Results

In all, 67 patients received afatinib plus bevacizumab, and 68 patients received erlotinib plus bevacizumab. Afatinib combined with bevacizumab had an objective response rate (ORR) of 82.1% and a disease control rate (DCR) of 97.0%, and the ORR and DCR were 83.8 and 95.6%, respectively, in the erlotinib combined with bevacizumab group (p = 0.798 and p = 1.000). The median progression-free survival was 20.7 and 20.3 months for the afatinib plus bevacizumab group and the erlotinib plus bevacizumab group, respectively [hazard ratio (HR) = 1.02; 95% confidence interval (CI), 0.891-1.953; p = 0.167). The overall survival was 41.9 and 51.0 months for the afatinib plus bevacizumab group and erlotinib plus bevacizumab group, respectively (HR = 1.42; 95% CI, 0.829-2.436; p = 0.201). The secondary EGFR-T790M mutation rates after disease progression were 44% in the afatinib plus bevacizumab group and 58.8% in the erlotinib plus bevacizumab group (p = 0.165). Skin toxicity was the most frequent treatment-related adverse event (AE) in both treatment groups. Diarrhea, an AE, occurred significantly more frequently in the afatinib plus bevacizumab group than in the erlotinib plus bevacizumab group (p < 0.05).

Conclusion

Afatinib combined with bevacizumab was equally as effective as erlotinib combined with bevacizumab for untreated advanced EGFR-mutated NSCLC. Prospective clinical studies that explore bevacizumab combined with afatinib or erlotinib for advanced EGFR-mutated NSCLC are warranted.

SUBMITTER: Lee SH

PROVIDER: S-EPMC9310205 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRamucirumab plus erlotinib (RAM + ERL) demonstrated superior progression-free survival (PFS) over placebo + ERL (PBO + ERL) in the phase III RELAY study of patients with epidermal growth factor receptor (EGFR)-mutated metastatic non-small-cell lung cancer (EGFR+ mNSCLC; NCT02411448). Next-generation sequencing (NGS) was used to identify clinically relevant alterations in circulating tumor DNA (ctDNA) and explore their impact on treatment outcomes.Patients and methodsEligible patients with EGFR+ mNSCLC were randomized 1 : 1 to ERL (150 mg/day) plus RAM (10 mg/kg)/PBO every 2 weeks. Liquid biopsies were to be prospectively collected at baseline, cycle 4 (C4), and postdiscontinuation follow-up. EGFR and co-occurring/treatment-emergent (TE) genomic alterations in ctDNA were analyzed using Guardant360 NGS platform.ResultsIn those with valid baseline samples, detectable activating EGFR alterations in ctDNA (aEGFR+) were associated with shorter PFS [aEGFR+: 12.7 months (n = 255) versus aEGFR-: 22.0 months (n = 131); hazard ratio (HR) = 1.87, 95% confidence interval (CI) 1.42-2.51]. Irrespective of detectable/undetectable baseline aEGFR, RAM + ERL was associated with longer PFS versus PBO + ERL [aEGFR+: median PFS (mPFS) = 15.2 versus 11.1 months, HR = 0.63, 95% CI 0.46-0.85; aEGFR-: mPFS = 22.1 versus 19.2 months, HR = 0.80, 95% CI 0.49-1.30]. Baseline alterations co-occurring with aEGFR were identified in 69 genes, most commonly TP53 (43%), EGFR (other than aEGFR; 25%), and PIK3CA (10%). PFS was longer in RAM + ERL, irrespective of baseline co-occurring alterations. Clearance of baseline aEGFR by C4 was associated with longer PFS (mPFS = 14.1 versus 7.0 months, HR = 0.481, 95% CI 0.33-0.71). RAM + ERL improved PFS outcomes, irrespective of aEGFR mutation clearance. TE gene alterations were most commonly in EGFR [T790M (29%), other (19%)] and TP53 (16%).ConclusionsBaseline aEGFR alterations in ctDNA were associated with shorter mPFS. RAM + ERL was associated with improved PFS outcomes, irrespective of detectable/undetectable aEGFR, co-occurring baseline alterations, or aEGFR+ clearance by C4. aEGFR+ clearance by C4 was associated with improved PFS outcomes. Monitoring co-occurring alterations and aEGFR+ clearance may provide insights into mechanisms of EGFR tyrosine kinase inhibitor resistance and the patients who may benefit from intensified treatment schedules.