Addition of Maintenance Therapy Did Not Meet Primary Endpoint in Lung Cancer Trial

The addition of pemetrexed to bevacizumab maintenance therapy after induction therapy for chemotherapy-naive patients with advanced non-squamous non–small-cell lung cancer did not meet the primary endpoint of overall survival, though the combination did trend towards longer progression-free survival (PFS).

The COMPASS study (abstract 9003), which was presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, included patients with wild-type, unknown, or non–deletion 19/non-L858R epidermal growth factor receptor status. Induction therapy consisted of carboplatin, pemetrexed, and bevacizumab. Patients who did not progress during induction therapy were randomized to a maintenance regimen of bevacizumab or bevacizumab plus pemetrexed.

“The maintenance strategy is well established in NSCLC with pemetrexed or bevacizumab, depending on what regimen you use in front of it, but not in combination. It’s not worth the toxicity,” said study discussant Ticiana Leal, MD, an assistant professor and thoracic oncology program leader at the University of Wisconsin.

“This is something that we really wanted to clearly know. Is adding a second agent in the maintenance setting better or not? A lot of times intuitively some would think that two is better than one in terms of disease control, response, and survival, but for whatever reason that does not always pan out,” she added.

In the study, 907 patients underwent induction therapy, and 621 went on to randomization; 594 were ultimately evaluable (299 in the bevacizumab plus pemetrexed arm and 295 in the bevacizumab-alone arm). The median age of patients was 65 years, and 72% were men; 60% and 40% had an ECOG performance status of 0 and 1, respectively; 83% had stage IV disease, and 91% were EGFR wild-type.

Among all patients, median progression-free survival was 7.1 months, and the 1-year PFS rate was 24.7%. Median overall survival was 21.1 months, the 1-year overall survival rate was 71.9%, and the 2-year rate was 43.8%.

The median overall survival was higher in the combination group (23.3 vs 19.6 months; hazard ratio [HR], 0.87), but the difference did not reach statistical significance (one-sided log-rank P = .069). A sub-analysis of patients with wild-type EGFR showed a significant improvement in overall survival with combination treatment (HR, 0.82; 95% CI, 0.68–0.99), and a longer median PFS in the combination group (5.7 vs 4.0 months; HR, 0.67; 2-sided P < .001). Improved overall survival was seen with combination maintenance treatment in patients under 70 years of age (HR, 0.792; 95% CI, 0.640–0.980).

About 87% of patients required additional therapy, and the researchers observed no new safety signals.