Survival benefits with erlotinib plus bevacizumab in EGFR-Mutated NSCLC

Sep 17 2014

By Lucy Piper, Senior medwireNews Reporter

Combining erlotinib with bevacizumab could prolong progression-free survival (PFS) in patients being treated for epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), phase II trial results suggest.

This addition of an angiogenesis inhibitor provides a strategy for extending PFS in these patients beyond about 12 months previously achieved with EGFR tyrosine-kinase inhibitor monotherapy, note the researchers.

“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 comment in The Lancet Oncology.

The study included 152 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.

Of these, 75 were randomly assigned to receive erlotinib 150 mg/day monotherapy, while 77 received erlotinib plus or bevacizumab 15 mg/kg every 3 weeks as first-line treatment until disease progression or toxicity.

The patients given combination treatment achieved significantly longer PFS than the patients treated with monotherapy, at a median of 16.0 versus 9.7 months (hazard ratio [HR]=0.54).

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 with 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”.

In a related comment, Rafael Rosell (Hospital Germans Trias I Pujol, Badalona, Spain) says that the increase in PFS the study “constitutes a new landmark in the treatment of patients with EGFR-mutant NSCLC”.

He adds that given the side effects relating to bevacizumab were “manageable”, the study “represents a novel therapeutic approach for optimising treatment for patients with EGFR-mutant NSCLC”.

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