S-1 combination therapy better improves outcome for gemcitabine-refractory pancreatic cancer than monotherapy
S-1* combination therapy was associated with a higher response rate and longer progression-free survival (PFS) than S-1 monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer, a new meta-analysis has found.
“Both combination regimens provided extraordinary results for patients with advanced [pancreatic cancer] who chose S-1 as the second-line therapy,” said the researchers.
Of the 623 patients included, 315 had undergone S-1 monotherapy and 308 underwent S-1 combination therapy. [Medicine (Baltimore) 2017;doi:10.1097/MD.0000000000007611]
Compared with patients undergoing S-1 monotherapy, those on S-1 combination therapy had a significantly higher response rate (RR, 1.75, 95 percent confidence interval [CI], 1.19–2.57; p=0.005) and longer PFS (hazard ratio [HR], 0.75, 95 percent CI, 0.62–0.91; p=0.005).
On subgroup analysis, better PFS was observed with S-1 combined with leucovorin (HR, 0.68; p=0.01) than irinotecan (CPT-11; HR, 0.77; p=0.16) or oxaliplatin (HR, 0.84; p=0.34), suggesting that the effect of S-1 plus leucovorin led to the longer PFS in the S-1 combination arm (HR, 0.75; p=0.005).
Additionally, S-1 combined with CPT-11 led to a higher response rate than S-1 monotherapy (RR, 3.07, 95 percent CI, 1.03–9.13).
“[T]he total dose and usage of [adjuvant] leucovorin might affect the final therapeutic efficacy … S-1 combined with both leucovorin and CPT-11 was a good therapeutic choice for [gemcitabine-refractory pancreatic cancer] patients,” said the researchers.
Both S-1 combination therapy and monotherapy were well tolerated with few adverse events such as neutropenia (n=26 and 22, respectively), diarrhoea (n=13 and 13), and nausea (n=14 and 8).
“A regimen that causes fewer adverse events can rapidly improve the physical and mental condition of the patient,” said the researchers, highlighting safety as an important consideration when introducing a new chemotherapeutic modality.
Overall, the findings suggest that both S1 monotherapy and combination therapy are potential alternatives to FOLFIRINOX**, the standard therapeutic regimen for gemcitabine-refractory pancreatic cancer, as it entails severe toxicity and side effects. [N Engl J Med 2011;364:1817-1825]
Furthermore, as most advanced pancreatic cancer cases entail local aggression or metastases, patients have a high likelihood of missing their chance for tumour resection, according to the researchers. Therefore, it is important to identify the therapeutic efficacy of various regimens that may help improve prognosis and guide therapeutic decisions for advanced pancreatic cancer, they added.
“[Both regimens] were practical and crucial in future clinical practice and clinical trials,” said the researchers, who called for further investigation to include other ethnicities as the study was limited to an Asian population.