Advanced gastric cancer patients may have better overall survival with mFOLFOX7 followed by mFOLFIRI

SAN FRANCISCO — First-line treatment with modified FOLFOX7 or modified FOLFIRI chemotherapy resulted in comparable progression-free survival and disease control rate among patients with locally advanced gastric adenocarcinoma, while a subgroup of patients who received mFOLFOX7 followed by mFOLFIRI had better overall survival, according to phase 2 study results presented at the Gastrointestinal Cancers Symposium.

Perspective from Daniel Chang, MD

“In this clinical trial we wanted to compare FOLFIRI and FOLFOX in advanced gastric cancer,” Feng Bi, MD, chairman of the committee of molecular targeted therapy and professor of oncology at West China Hospital of Sichuan University, said during his presentation. The primary endpoint was PFS, and secondary endpoints were OS and disease control rate, he said.

Feng Bi

Aiming to compare mFOLFIRI and mFOLFOX7 as first-line therapies, Bi and colleagues performed an open, randomized study of patients with measurable metastatic or recurrent gastric adenocarcinoma who had not received prior treatment. First-line mFOLFIRI was received every 2 weeks by arm A (n = 54) for whom mFOLFOX7 was the second-line treatment, and vice-versa for arm B (n = 74). Progression-free survival served as the primary endpoint, while overall survival, disease control rate and toxicity served as secondary endpoints.

The researchers found there was no significant difference in progression-free survival between groups. The median progression-free survival rate was 2.9 (range, 1.9-4.1) months for arm A compared with 4.1 (range, 3.2-4.8) months for arm B (P = .109).

Furthermore, there was no significant difference in disease control rate between groups (59.3% vs. 66.3%; P = .85).

The median overall survival was also not significantly different between groups (9.9 [range, 6-13.5] months vs. 12 [range, 10.3-13.7] months; P = .431). However, in the subgroup of patients who completed both treatment lines per protocol, median overall survival was 11 (range, 5.1-16.9) months for those who received first-line mFOLFIRI and second-line mFOLFOX7, compared with 20.2 (range, 13.4-26.6) months for those who received first-line mFOLFOX7 and second-line mFOLFIRI (P = .03).

Both regimens were well-tolerated and toxicity was acceptable, Bi said. Grade 3/4 adverse events occurred in 53.2% of arm A and in 55.4% of arm B.

“In conclusion, there was no significant difference in the PFS and disease control rate for FOLFOX7 and FOLFIRI as first line treatment for advanced gastric cancer,” Bi said. “However, modified FOLFOX7 followed by modified FOLFIRI might have a better OS, which needs a large sample to validate.” – by Adam Leitenberger

Reference:

Bi F, et al. Abstract 01. Presented at: Gastrointestinal Cancers Symposium; Jan. 21-23, 2016; San Francisco.

Disclosure: The researchers report no relevant financial disclosures.

Perspective

Daniel Chang, MD

This was a phase 2 trial that randomized patients with advanced gastric cancer to modified FOLFOX7 vs. modified FOLFIRI, and for patients who progressed, second-line treatment using the opposite regimen was given. About 200 patients were enrolled and about 130 patients were ultimately included for analysis.

The main findings of the trial were that there was no difference in terms of protocol adherence or in terms of overall survival. However, on subgroup analysis, they found that — for patients who completed both first-line and second-line chemotherapy regimens — overall survival improved for patients who started with modified FOLFOX7 and then received modified FOLFIRI vs. patients who started with modified FOLFIRI and then received modified FOLFOX7.

The median survival was 20 months vs. about 11 months. That is certainly a large difference in overall survival, and these results, at this point, are at best hypothesis generating, but certainly suggest that of starting with FOLFOX chemotherapy, with FOLFIRI as a salvage regimen should be the standard of care. I think further testing will be needed to determine if this superior survival is indeed true.

Daniel Chang, MD

Associate Professor of Radiation Oncology

Stanford University

Disclosures: Chang reports no relevant financial disclosures.