TAS-118 + oxaliplatin outdoes S-1 + cisplatin in improving survival in advanced gastric cancer
The combination of TAS-118 and oxaliplatin led to significantly greater survival compared with the S-1 and cisplatin combination in patients with metastatic or recurrent HER2-negative gastric cancer, the phase III SOLAR* study showed.
The study population comprised 711 treatment-naïve patients with metastatic or recurrent HER2-negative gastric cancer and an ECOG score of 0–1 from Japan and Korea. They were randomized to receive either TAS-118 (S-1 [40–60 mg] and leucovorin [25 mg] BID) for 7 days plus oxaliplatin (85 mg/m2) on day 1 every 2 weeks (n=356) or S-1 (40–60 mg BID) for 21 days plus cisplatin (60 mg/m2) on day 1 or day 8** every 5 weeks (n=355).
When assessed following 491 events, overall survival (OS) was significantly longer in the TAS-118 plus oxaliplatin compared with the S-1 plus cisplatin group (median 16.0 vs 15.1 months, hazard ratio [HR], 0.83, 95 percent confidence interval [CI], 0.69–0.99; p=0.039). [ESMO GI 2019, abstract LBA-003]
Progression-free survival (PFS) was also significantly longer among patients assigned to TAS-118 plus oxaliplatin compared with those assigned to S-1 plus cisplatin (median 7.1 vs 6.4 months, HR, 0.79, 95 percent CI, 0.66–0.93; p=0.005). The overall response rate (ORR) was also superior among patients assigned to TAS-118 plus oxaliplatin than S-1 plus cisplatin (73.5 percent vs 50.0 percent; p<0.001).
The overall incidence of grade ≥3 adverse events (AEs) was comparable between TAS-118 plus oxaliplatin and S-1 plus cisplatin recipients (69.6 percent vs 69.3 percent). However, the most common grade 3–4 AEs occurred more frequently in TAS-118 plus oxaliplatin than S-1 plus cisplatin recipients, namely diarrhoea (9.4 percent vs 4.3 percent), peripheral sensory neuropathy (8.5 percent vs 0.3 percent), weight loss (5.4 percent vs 2.9 percent), and stomatitis (3.7 percent vs 1.4 percent). Two treatment-related deaths occurred in the TAS-118 plus oxaliplatin group.
The SOLAR study follows a previous phase II study that hinted at the superior response of S-1 plus leucovorin and oxaliplatin in advanced gastric cancer over a S-1 plus cisplatin combination. [Lancet Oncol 2016;17:99-108]
“A fluoropyrimidine plus platinum combination has been used as the standard first-line chemotherapy for advanced gastric cancer,” said Professor Yoon-Koo Kang from the Asan Medical Center, Seoul, Republic of Korea, at ESMO GI 2019.
“In summary, the phase III SOLAR study demonstrated better efficacy of TAS-118 plus oxaliplatin compared to S-1 plus cisplatin in advanced gastric cancer, with a better OS, PFS, and ORR … We can conclude that TAS-118 plus oxaliplatin can be a new standard first-line regimen for the treatment of advanced gastric cancer,” he said.