Second-line chemo regimen offers survival benefit in pancreatic cancer
The combination of irinotecan, fluoropyrimidine (FP), and folinic acid (FA) offered progression-free survival (PFS) and overall survival (OS) benefit as second-line treatment for patients with metastatic pancreatic cancer after first-line gemcitabine-based chemotherapy, according to a meta-analysis.
The eight randomized studies included in the analysis comprised 1,587 patients (mean age 63.7 years, 56.8 percent male) receiving second-line chemotherapy following gemcitabine-based first-line chemotherapy. The second-line chemotherapeutic agents evaluated were various combinations of irinotecan, FP, FA, and oxaliplatin. [Oncotarget 2018;9:29801-29809]
The combination of irinotecan-FP-FA bested all other combinations* used especially FP and FP-oxaliplatin in terms of PFS (hazard ratio [HR], 0.37 and HR, 0.31, respectively) and OS (HR, 0.55 and HR, 0.57, respectively).
Moreover, the irinotecan-FP-FA combination had the largest probability of being the best and average rank among all other combinations (mean, 1.56 and mean, 2.53 for PFS and OS, respectively).
These findings highlight the favourable survival benefit of a regimen that includes irinotecan as opposed to evidence underscoring the lack of significant survival benefit when using a second-line regimen based on either oxaliplatin or irinotecan. [Eur J Cancer 2017;81:174-182]
The results also concur with a previous meta-analysis which showed that regimens including FP were suitable treatment alternatives for disease progression after a gemcitabine-based chemo regimen, [Cancer 2017;123:4680-4686] as well as with other trials reflecting improved OS in patients who received a second-line regimen after nab-paclitaxel/gemcitabine. [Br J Cancer 2016;115:188-194; J Clin Oncol 2016;34:4124; J Clin Oncol 2013;31:23-29]
Although gemcitabine monotherapy has been the cornerstone of first-line treatment for over 15 years, disease progression still warrants a second line of defence, noted the researchers. The Food and Drug Administration has approved irinotecan combined with 5-FU (fluorouracil) and FA, while the American Society of Clinical Oncology recommended FP alone or in combination with oxaliplatin or irinotecan as second-line chemotherapeutic alternatives. [J Clin Oncol 2016;34:2784-2796]
Nonetheless, results should be interpreted with caution considering that most of the trials were conducted in China and Japan, noted the researchers. “[T]he literature [reflects] evidence of heterogeneity between Western and Eastern countries in cancer treatment and in patient’s response,” they said. [J Clin Oncol 2011;29:4387-4393; Lancet 2012;379:315-321]
The researchers also recommended more randomized trials to establish the ideal second-line regimen for pancreatic cancer, which has a poor prognosis despite recent advances in cancer treatment. “[A]dditional indication for second-line treatment will depend on enhanced identification of biologic predictors of second-line therapy benefit, development of more active regimens, and investigation of the specific toxicity of each regimen.”