No OS Gain When Bevacizumab Is Added To Adjuvant Chemotherapy for Early-Stage NSCLC

The E1505 trial has failed to show a survival benefit with bevacizumab for patients receiving chemotherapy after surgery for early-stage non-small-cell lung cancer

medwireNews: Phase III trial results indicate that bevacizumab does not improve overall survival (OS) for patients undergoing platinum-based chemotherapy after surgery for early-stage non-small-cell lung cancer (NSCLC).

“Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC”, the E1505 investigators conclude in The Lancet Oncology.

The open-label study included 1501 patients with completely resected stage IB–IIIA NSCLC who were randomly assigned to receive four cycles of cisplatin plus an investigators’ choice of vinorelbine, docetaxel, gemcitabine or pemetrexed alone (n=749), or alongside bevacizumab 15 mg/kg given every 21 days for 1 year (n=752).

After a median follow-up of 50.3 months, the estimated OS was not reached in the chemotherapy-only arm of the study and was 85.8 months in the bevacizumab arm. The hazard ratio (HR) for survival did not significantly differ between the groups.

The estimated median disease-free survival times were also comparable in the two arms, at 42.9 and 40.6 months, respectively, and the investigators failed to identify any subgroups of patients who benefited from bevacizumab, although they note that post-hoc analysis of the chemotherapy subgroups is yet to mature.

Patients given bevacizumab had higher rates of grade 3–5 toxicity than those given only chemotherapy (83 vs 67%), including hypertension (30 vs 8%) and neutropenia (37 vs 33%).

Three of the 15 deaths in the chemotherapy group were attributed to treatment compared with 10 of the 19 deaths in the bevacizumab group, including two cases of lung infection and single episodes of multi-organ failure, febrile neutropenia, sudden death, myocardial infarction and bronchopulmonary haemorrhage.

Heather Wakelee, from Stanford Cancer Institute in California, USA, and E1505 co-investigators therefore conclude: “[F]our cycles of cisplatin-based adjuvant chemotherapy should remain the standard of care for patients with resected stage II and IIIA NSCLC, and is also considered an appropriate treatment option for many patients with resected stage IB NSCLC with large tumours (≥4 cm).”

Jared Weiss, from Lineberger Comprehensive Cancer Center at the University of North Carolina in Chapel Hill, USA, writes in an accompanying comment that the trial results “can direct clinical efforts away from bevacizumab and cytotoxic regimen choice.”

He notes that the PACIFIC trial findings showed a survival advantage for the PD-L1 inhibitor durvalumab for stage III NSCLC, and awaits the forthcoming results for two trials of NSCLC patients with mutations – the ALCHEMIST comparison of erlotinib or crizotinib versus placebo, and the ANVIL trial of nivolumab versus placebo.

“Together, these trials might provide further direction to improved treatment regimens for patients with non-metastatic NSCLC”, the commentator believes.

References

Wakelee HA, Dahlberg SE, Keller SM, et al. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol; Advance online publication 9 November 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30691-5

Weiss J. in adjuvant treatment of non-small-cell lung cancer. Lancet Oncol; Advance online publication 9 November 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30843-4

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