Adjuvant Pemetrexed Plus Cisplatin: A Safer Option for Non-Squamous NSCLC?

Adjuvant treatment with pemetrexed/cisplatin was not found to be superior to vinorelbine/cisplatin, but was better tolerated, in patients with non-squamous non–small-cell lung cancer (NS-NSCLC), according to new data from the JIPANG phase III study that were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract 8501), held May 31–June 4 in Chicago.

In addition, a subanalysis showed that patients with epidermal growth factor receptor (EGFR) mutations in the pemetrexed/cisplatin arm had better recurrence-free survival (RFS) than patients with EGFR mutations in the vinorelbine/cisplatin arm.

“Although this phase III study did not meet the primary endpoint, pemetrexed/cisplatin had a similar efficacy to vinorelbine/cisplatin with a better tolerability as postoperative adjuvant chemotherapy for NS-NSCLC patients,” the researchers wrote in the abstract.

Despite the lack of superiority, the combination has its place in therapy, according to Jamie Chaft, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, who served as a discussant during the session. “This negative study, like those before it, supports the use of cisplatin plus pemetrexed in the adjuvant setting,” she said.

Previous phase III studies showed that cisplatin-based adjuvant chemotherapy leads to better outcomes in resected NSCLC, but questions remain as to which platinum therapy is the most effective in this setting. However, subanalyses of large, randomized phase III trials suggest that pemetrexed may be effective in NS-NSCLC.

From March 2012 through August 2016, the researchers randomized 804 patients with NS-NSCLC to receive pemetrexed/cisplatin or vinorelbine/cisplatin, which was a large enough sample size to potentially demonstrate superiority of pemetrexed/cisplatin. Patients had to be pathological stage II to IIIA and were performance status 0 to 1.

The median age was the same in both groups (65 years), as was the percentage of patients with stage IIIa disease (52%) and adenocarcinoma (96%). Nearly identical numbers of patients had EGFR mutations (24% vs 25%). Patients received treatment every 3 weeks for up to 4 cycles.

Over a median follow-up of 45.2 months, there was no significant difference in RFS (median of 38.9 months for pemetrexed/cisplatin vs 37.3 months for vinorelbine/cisplatin). However, patients with EGFR mutations in the pemetrexed/cisplatin arm fared better than patients with wild-type EGFR in the vinorelbine/cisplatin group (hazard ratio [HR], 1.38 vs 0.87; interaction P = .046).

At 3 years, the two groups had similar overall survival (83.5% vs 87.2%). Subjects in the pemetrexed/cisplatin group were more likely to complete all 4 cycles of therapy (87.9% vs 72.7%; P < .001) and experienced lower frequencies of grade 3 to 5 adverse events (47.4% vs 89.4%; P < .001), hematologic adverse events (24.7% vs 81.8%; P < .001), grade 3 or 4 febrile neutropenia (0.3% vs 11.6%; P < .05), grade 3/4 neutropenia (22.8% vs 81.1%; P < .05), and grade 3/4  anemia (2.8% vs 9.3%; P < .05), as well as alopecia of any grade (2.3% vs 25.8%; P < 0.05).

There was one treatment-related death in each arm, and pemetrexed/cisplatin was associated with a higher treatment completion rate (87.9% vs 72.7%; P < .001).