Bevacizumab Does Not Improve Outcomes With Chemotherapy in Early NSCLC

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The addition of bevacizumab to adjuvant chemotherapy failed to improve survival outcomes in patients with surgically resected early-stage NSCLC.

The addition of bevacizumab to adjuvant chemotherapy failed to improve survival outcomes in patients with surgically resected early-stage non–small-cell lung cancer (NSCLC), according to a new randomized trial. The agent “does not have a role” in this setting, the investigators concluded.

“In the setting of advanced-stage NSCLC, the first agent to improve survival when added to a platinum doublet was bevacizumab,” wrote authors led by Heather A. Wakelee, MD, of the Stanford Cancer Institute at Stanford University in California. The researchers tested whether the VEGF-targeted agent would be similarly effective in the early-stage NSCLC adjuvant setting, where patients remain at high risk of relapse despite chemotherapy.

The trial was an open-label, randomized, phase III study including 1,501 patients with completely resected stage IB to IIIA NSCLC. They were randomized to receive either chemotherapy alone (749 patients) or chemotherapy plus bevacizumab (752 patients); results were published in Lancet Oncology.

Patients had a median age of 61 years, and were evenly divided between men and women. Most patients were white (86% in the chemotherapy-alone group, 88% in the bevacizumab group), and four different chemotherapy regimens were used in largely even proportions (cisplatin along with either vinorelbine, docetaxel, gemcitabine, or pemetrexed).

The trial was stopped after a sixth planned interim analysis. At that point, the median follow-up for patients still alive was 50.3 months. The median overall survival with chemotherapy alone was not yet reached, and with bevacizumab it was 85.8 months; this yielded a hazard ratio (HR) for survival of 0.99 (95% CI, 0.82–1.19; P = .90).

The median disease-free survival was also similar, at 42.9 months without bevacizumab and 40.6 months with it, for an HR of 0.99 (95% CI, 0.86–1.15; P = .95). Subgroup analyses did not reveal many significant differences between the treatments. Patients treated with cisplatin/vinorelbine fared slightly better with chemotherapy alone, with an HR for disease-free survival of 1.37 (95% CI, 1.02–1.86), while those treated with cisplatin/pemetrexed did better with bevacizumab, with an HR of 0.72 (95% CI, 0.55–0.94).

Toxicities of grades 3–5 that occurred more frequently with bevacizumab than without it included hypertension in 30% of patients compared with 8%, and neutropenia in 37% compared with 33%. There were 15 deaths on treatment in the chemotherapy-alone group, and 19 deaths in the bevacizumab group.

“Four 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 tumors,” the authors concluded. They noted that other trials are ongoing to find additional treatments in this setting, including with immune checkpoint inhibitors. This trial, though, “provides supportive evidence that bevacizumab should not be used in the adjuvant setting for resected early-stage NSCLC.”

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