S-1 plus cisplatin improves PFS in patients with advanced cervical cancer
S-1 in combination with cisplatin does not appear to be superior to cisplatin alone in terms of overall survival (OS), but it markedly increases progression-free survival (PFS) in patients with stage IVB, recurrent or persistent cervical cancer, according to a study.
“S-1 plus cisplatin did not improve OS over cisplatin alone. However, adding S-1 to cisplatin significantly prolonged OS in patients with better physical condition. Moreover, S-1 in combination with cisplatin significantly improved PFS and ORR [overall response rate] over cisplatin alone,” researchers said.
Of the 375 patients enrolled, 364 were randomized to S-1 plus cisplatin (n=188; study group) or cisplatin alone (n=176; control group). Cisplatin 50 mg/m2 was administered on day 1 in both groups in each cycle. In the study group, S-1 was administered orally at 80–120 mg daily on days 1–14 of a 21-day cycle. OS was the primary endpoint.
Median OS in the study group was 21.9 months and 19.5 months in the control group (hazard ratio [HR], 0.84; 95 percent CI, 0.67–1.05; p=0.125). Median PFS in the study and control groups was 7.3 and 4.9 months, respectively (HR, 0.62; 0.48–0.80; p<0.001). [Br J Cancer 2018;doi:10.1038/s41416-018-0206-7]
The study group had an increased rate of adverse event (AE) despite the absence of any unexpected AEs, according to researchers.
Of note, S-1 plus cisplatin significantly prolonged PFS to 7.3 months, while other phase III studies reported median PFS of 3.98–6.9 months with cisplatin-based doublet combination and 8.2 months with paclitaxel and cisplatin combined with bevacizumab. [J Clin Oncol 2009;27:4649-4655; J Clin Oncol 2015;33:2129-2135; N Engl J Med 2014;370:734-743]
“Although the patients’ quality of life data are lacking in this study, S-1 plus cisplatin demonstrated a similar response in terms of PFS to these combination therapies. ORR was also significantly improved with S-1 in combination with cisplatin,” researchers said.
Additionally, cisplatin-based doublet combinations or paclitaxel and cisplatin combined with bevacizumab resulted in response rates of 27–48 percent. S-1 plus cisplatin yielded a complete response rate of 12.4 percent, which was comparable to cisplatin plus paclitaxel plus bevacizumab. [J Clin Oncol 2005;23:4626-4633; J Clin Oncol 2004;22:3113-3119; N Engl J Med 2014;370:734-743]
Stage IVB, recurrent or persistent cervical cancer is rarely curable, which is why selection of combination chemotherapy that considers the toxicity profile and patient preference is important, according to researchers.
“For example, alopecia may worsen a patient’s quality of life and lead to interference with treatment. Alopecia occurred in 64.3 percent of patients treated with paclitaxel plus cisplatin. In contrast, 8 percent of patients experienced grade 1, but not grade 2, alopecia with S-1 plus cisplatin in this study,” they said.
“Given that the standard therapy for this population has changed in the course of this study, further studies [using] combination therapy as a comparator are warranted to confirm the clinical positioning of S-1 combined with cisplatin for this population,” they added.