New research has concluded that adding pemetrexed (Alimta; Eli Lilly and Company) to bevacizumab (Avastin; Genentech) for continuous maintenance therapy significantly prolongs overall survival relative to bevacizumab alone in patients with advanced non-squamous non-small cell lung cancer (NSCLC) without sensitizing EGFR mutations, according to data presented at the American Society of Clinical Oncology (abstract 9003) annual meeting.
A multi-center team of Japanese researchers noted that previous research has demonstrated the efficacy of two continuous maintenance therapies -- pemetrexed after pemetrexed plus platinum chemotherapy and bevacizumab after bevacizumab plus platinum doublet chemotherapy -- in prolonging survival among patients with advanced nonsquamous NSCLC. Nevertheless, data regarding the addition of pemetrexed to bevacizumab have been lacking.
Cancer cells. Source: Getty
To help shed light on this relationship, the researchers -- led by principal investigator Takashi Seto, MD of the National Kyushu Cancer Center in Fukuoka, Japan -- undertook what they call the COMPASS trial: COntinuous Maintenance of bevacizumab with or without Pemetrexed for advanced non-Squamous non-Small cell lung cancer (UMIN000004194).
As part of the study, they identified patients with previously untreated advanced nonsquamous NSCLC whose EGFR status was either wild-type, unknown, or other than Del19 or L858R.
Each of the participants underwent induction therapy with carboplatin (AUC=6), pemetrexed (500 mg/m2), and bevacizumab (15mg/kg) every three weeks for a total of four cycles. Individuals who did not demonstrate any progression during the induction therapy were then randomized in a 1:1 ratio to receive maintenance therapy using either bevacizumab alone or bevacizumab plus pemetrexed.
The study’s primary endpoint was overall survival from the time of randomization.
As Dr. Seto and colleagues reported, the study identified 907 patients who underwent induction therapy between September 2010 and September 2015. Of those, 621 patients were randomized.
Five individuals did not receive study treatment and 22 did not meet the eligibility criteria, leaving a total of 594 evaluable patients: 295 in the bevacizumab arm and 299 in the bevacizumab plus pemetrexed arm. The median age of the participants was 65 years and 72% were male. Eighty-three percent had stage IV NSCLC; 91% were wild-type EGFR, while 7% were of other EGFR status.
The study found that median overall survival was 23.3 months among patients who received the combination maintenance therapy, compared with 19.6 months among those who received maintenance therapy with bevacizumab alone (HR = 0.87; 95% CI, 0.72-1.04; p=0.069).
Among patients with wild-type EGFR tumors, the hazard ratio for overall survival was found to be 0.82 (95% CI, 0.68-0.99) favoring maintenance treatment with pemetrexed and bevacizumab.
Similarly, median progression-free survival was found to be 5.7 months who received the combination maintenance therapy, compared with 4.0 months for their counterparts who received bevacizumab alone (HR = 0.67; 95% CI, 0.57-0.79). Interestingly, 87.4% of patients received subsequent therapy.
No new safety signals were observed as part of the trial.
The investigators noted that the study’s primary analysis was not met. “However,” they wrote, “the incorporation of pemetrexed significantly prolonged overall survival in patients with wild-type EGFR.”