Results from a new phase III study have found that the combination of pemetrexed (Alimta; Eli Lilly & Company) and cisplatin is as effective as vinorelbine and cisplatin as postoperative adjuvant chemotherapy in patients with completely resected stage II-IIIA non-squamous non small-cell lung cancer (NSCLC). 

The multi-center team of Japanese researchers also concluded that pemetrexed and cisplatin had better tolerability than the vinorelbine-cisplatin combination.

Chemotherapy. Source: Getty

According to data presented at the American Society of Clinical Oncology Annual Meeting (abstract 8501), the investigators described the need for the trial. “Although previous trials demonstrated the efficacy and safety of postoperative cisplatin-based adjuvant chemotherapy for resected NSCLC,” they noted, “no phase III study has so far evaluated pemetrexed-cisplatin in this population.”

To help fill this void, the researchers enrolled 804 patients with completely resected, pathological stage II-IIIA nonsquamous NSCLC into the trial. Between March 2012 and August 2016, these individuals were randomized in a 1:1 ratio to receive either 500 mg/m2 pemetrexed and 75 mg/m2 cisplatin on day 1 or 25 mg/m2 vinorelbine on days 1 and 8 and 80 mg/m2 cisplatin on day 1. Patients were stratified according to age, sex, pathologic stage, EGFR mutation status, and institution. 

The trial’s primary endpoint was recurrence-free survival. 

A total of 784 patients were available for the final efficacy analysis, 389 in pemetrexed/cisplatin group and 395 in the vinorelbine/cisplatin group. Patients’ median age was 65 years, 52% had stage III disease, and 96% had adenocarcinoma. EGFR mutation was present in 24% of patients in the pemetrexed group and 25% in the vinorelbine group. 

Over a median follow-up of 45.2 months, median recurrence-free survival was found to be 38.9 months among pemetrexed/cisplatin patients, compared with 37.3 months in their counterparts receiving vinorelbine/cisplatin (HR = 0.98; 95% CI, 0.81-1.2).

Interestingly, recurrence free survival was 38% higher among patients in the pemetrexed/cisplatin group who had EGFR mutations (HR = 1.38; 95% CI, 0.95-1.99). Conversely, patients without such mutations had 13% lower rates of recurrence-free survival when treated with pemetrexed and cisplatin (HR = 0.87; 95% CI, 0.69-1.09). 

Overall survival rate at three years was 83.5% among patients treated with pemetrexed and cisplatin, compared with 87.2% for those in the vinorelbine/cisplatin group (HR = 0.98; 95% CI, 0.71-1.35). 

Side-effect profile favored the pemetrexed/cisplatin combination, as patients in that group were found to have lower rates of grade 3 or 4 febrile neutropenia (0.3% vs 11.6%; P < .001), neutropenia (22.8% vs 81.1%; P < .001), anemia (2.8% vs 9.3%; P < .001), and alopecia of any grade (12.8% vs 30.1%; P < .001). One treatment-related death was observed in each arm. 

Perhaps not surprisingly, the overall rate of treatment completions favored pemetrexed and cisplatin, as 87.9% of individuals in that group completed therapy, compared with 72.7% of those treated with vinorelbine and cisplatin (P < .001). 

The researchers concluded that while the trial failed to meet its primary endpoint, pemetrexed and cisplatin still proved comparable to vinorelbine/cisplatin, with a better tolerability profile. “A significant interaction for recurrence-free survival was found between treatment and EGFR mutation status,” they added.