Bevacizumab Plus Erlotinib ‘New Landmark’ For EGFR-Mutated NSCLC

NSCLC patients may benefit from angiogenesis inhibitor plus EGFR tyrosine kinase inhibitor combination

medwireNews: Phase II trial results suggest that the addition of bevacizumab to erlotinib could improve the progression-free survival (PFS) of patients being treated for epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC).

The 75 patients given the anti-angiogenic monoclonal antibody plus erlotinib achieved significantly longer PFS than the 77 patients treated with the EGFR-tyrosine kinase inhibitor alone, at a median of 16.0 versus 9.7 months (hazard ratio [HR]=0.54).

“The increase in [PFS] constitutes a new landmark in the treatment of patients with EGFR-mutant NSCLC”, writes Rafael Rosell, from Hospital Germans Trias I Pujol in Badalona, Spain, in a comment in The Lancet Oncology.

Noting that side effects from the combined treatment were “manageable”, he says the study’s “compelling findings” represent “a novel therapeutic approach for optimising treatment for patients with EGFR-mutant NSCLC.”

The study included patients with stage IIIB or IV non-squamous NSCLC with activating EGFR mutations, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior chemotherapy for advanced disease.

Patients were randomly assigned to receive erlotinib 150 mg/day as monotherapy or alongside bevacizumab 15 mg/kg every 3 weeks as first-line treatment until disease progression or toxicity.

Study authors Nobuyuki Yamamoto, from Wakayama Medical University in Japan, and team report that PFS was better with combined treatment than erlotinib monotherapy regardless of age, gender, smoking status, tumour stage or performance status.

Analysis by EGFR mutation subtype indicated that combined therapy was significantly better than monotherapy for patients with an exon 19 deletion (median PFS, 18.0 vs 10.3 months). There was also a trend towards improved survival for bevacizumab plus erlotinib for patients with an exon 21 Leu858Arg mutation, although this did not reach significance (13.9 vs 7.1 months).

Objective responses were achieved by 69% of patients given bevacizumab plus erlotinib and 64% of erlotinib only patients, although disease control was significantly higher with the combined treatment (99 vs 88%).

And 8% of patients in the erlotinib monotherapy group experienced progressive disease compared with none of the combination treatment group.

Combined treatment was associated with a higher rate of grade 3 or 4 adverse events than monotherapy (91 vs 53%) including a “substantially” higher rate of hypertension, bleeding and proteinuria.

But the rate of serious adverse events was comparable in the treatment groups and erlotinib intensity and discontinuation rates were also similar. Bevacizumab was discontinued by 41% of patients due to side effects but the researchers note that most events were “nonserious and reversible”.

Nobuyuki Yamamoto et al therefore conclude: “Our findings suggest that the combination of erlotinib and bevacizumab could be a new first-line regimen in EGFR mutation-positive NSCLC, and that further investigation of the regimen is warranted.”

They add: “Two clinical trials, BELIEF (NCT01562028) and ACCRU RC1126 (NCT01532089), are ongoing and the results are awaited to confirm the efficacy and safety shown in our study.”


Seto T, Kato T, Nishio M, et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre phase 2 study. Lancet Oncol 2014; Early online publication 28 August. doi:10.1016/S1470-2045(14)70381-X

Rosell R.What new therapeutic targets exist for EGFR-mutant NSCLC? Lancet Oncol 2014; Early online publication 28 August. doi:10.1016/S1470-2045(14)70386-9

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