Adding bevacizumab to frontline treatment with erlotinib significantly prolonged progression-free survival (PFS) in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC), according to phase 3 results published in Cancer Cell.

The phase 3 ARTEMIS-CTONG1509 trial (ClinicalTrials.gov Identifier: NCT02759614) enrolled 311 patients in China who had EGFR-mutated (exon 19 deletion or exon 21 L858R mutation), advanced NSCLC.

Patients were randomly assigned to receive bevacizumab plus erlotinib (157 patients) or erlotinib (154 patients) until disease progression, intolerable toxicity, or consent withdrawal.


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The independent review committee (IRC)-assessed PFS was 17.9 months in the bevacizumab-erlotinib arm and 11.2 months in the erlotinib arm (hazard ratio [HR], 0.55; 95% CI, 0.41-0.73; P <.001).

Among patients with exon 21 L858R mutations, the IRC-assessed PFS was 19.5 months in the combination arm and 9.7 months in the erlotinib arm (HR, 0.50; 95% CI, 0.32-0.77; P =.001). Among patients with exon 19 deletion, the IRC-assessed PFS was 17.7 months and 12.5 months, respectively (HR, 0.62; 95% CI, 0.42-0.93; P =.017).

Patients with brain metastases at baseline had a significant improvement in median PFS with bevacizumab-erlotinib over erlotinib alone — 17.9 months and 11.1 months, respectively (HR, 0.48; 95% CI, 0.27-0.84; P =.008).

However, in the entire cohort, the median overall survival (OS) was not significantly different between the combination arm and the monotherapy arm — 36.2 months and 31.6 months, respectively (HR, 0.92; 95% CI, 0.69-1.23; P =.581).

At 2 years, the OS rate was 70.1% in the combination arm and 64.6% in the erlotinib arm (P =.317). At 3 years, the OS rates were 51.1% and 46.3%, respectively (P =.424).

The researchers found that, overall, the toxicity associated with bevacizumab plus erlotinib was manageable and tolerable, and there were no new safety signals.

However, grade 3 or higher treatment-emergent adverse events (AEs) were more common in the combination arm than in the monotherapy arm — 54.8% and 26.1%, respectively.

Furthermore, the rate of discontinuation due to AEs was higher in the bevacizumab-erlotinib arm than in the erlotinib-alone arm — 7.0% and 3.3%, respectively.

The most common AEs resulting in discontinuation of bevacizumab were proteinuria (10.2%), hypertension (2.5%), cerebral hemorrhage (1.3%), and oral bleeding (1.3%).

There was 1 AE-related death reported in each treatment arm.

“Despite the lack of OS benefit, this combination regimen can be considered as one of the therapeutic options for first-line treatment of patients with advanced EGFR-mutated NSCLC, particularly those who present with baseline CNS [central nervous system] metastasis or those who harbor ex21 L858R.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Zhou Q, Xu CR, Cheng Y, et al. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell. Published online August 12, 2021. doi:10.1016/j.ccell.2021.07.005