From the Journals

Combo maintenance boosts PFS, not OS, in advanced NSCLC



Adding pemetrexed to bevacizumab maintenance improved progression-free survival (PFS), but not overall survival (OS), in a phase 3 trial of patients with advanced nonsquamous non–small cell lung cancer (NSCLC).

However, the addition of pemetrexed to bevacizumab maintenance improved OS for patients with wild-type EGFR, reported Takashi Seto, MD, of the National Kyushu Cancer Center, Japan, and colleagues. Their report was published in the Journal of Clinical Oncology.

The researchers conducted a phase 3 trial of 599 patients with previously untreated, advanced nonsquamous NSCLC. Patients were randomly allocated to receive maintenance with either pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) or bevacizumab alone (15 mg/kg once every 3 weeks).

Prior to starting maintenance, patients received induction with carboplatin, pemetrexed, and bevacizumab. Both interventions were maintained until unacceptable toxicity, disease progression, death, or withdrawal for other reasons.

The primary outcome was OS, measured from the time of randomization until death from any cause. Secondary outcomes included PFS and safety.


Overall, there was no significant difference in OS between the treatment arms. The median OS was 23.3 months in the pemetrexed-bevacizumab arm and 19.6 months in the bevacizumab arm (hazard ratio, 0.87; P = .069).

However, OS was significantly prolonged for patients with wild-type EGFR who received pemetrexed plus bevacizumab. The median OS was 23.3 months in the pemetrexed-bevacizumab arm and 18.8 months in the bevacizumab arm (HR, 0.82; P = .020).

For the entire cohort, PFS was significantly better in the pemetrexed-bevacizumab arm. The median PFS was 5.7 months in the pemetrexed-bevacizumab arm and 4.0 months in the bevacizumab arm (HR, 0.67; P < .001).


In the pemetrexed-bevacizumab arm, the most common grade 3 or higher adverse events were low neutrophil count (14.0%), hypertension (11.7%), and low white blood cell count (5.4%).

Treatment-related deaths occurred in four patients receiving pemetrexed-bevacizumab maintenance. The causes of death were interstitial pneumonitis (n = 2), alveolar hemorrhage, and lung infection.

“The safety profile obtained in this study was predictable and similar to previous reports,” the researchers wrote. They acknowledged that bevacizumab-induced hypertension was commonly observed but was not problematic from a clinical perspective.

Based on these results, the researchers concluded that pemetrexed plus bevacizumab maintenance is “useful” in patients with advanced nonsquamous NSCLC, especially in patients with wild-type EGFR.

This study was supported, in part, by Eli Lilly Japan KK. The authors disclosed financial affiliations with Eli Lilly and other companies.

SOURCE: Seto T et al. J Clin Oncol. 2020 Mar 10;38(8):793-803.

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