Similar efficacy between GNP, FOLFIRINOX in pancreatic cancer

Audrey Abella
27 Feb 2018
Similar efficacy between GNP, FOLFIRINOX in pancreatic cancer

The combination regimen comprising gemcitabine and nab*-paclitaxel (GNP) exhibited similar potential with FOLFIRINOX** in downstaging and improving survival rates in pancreatic cancer, according to several studies presented at the ASCO Gastrointestinal Cancers Symposium 2018 (ASCO GI 2018).

Interim results from the NEOLAP*** trial revealed similar findings among patients with nonresectable pancreatic ductal adenocarcinoma (PDAC) who were randomized to receive two cycles of GNP (n=42) or four cycles of FOLFIRINOX (n=44) after an initial two cycles of GNP, where similar disease control rates were observed in the GNP and FOLFIRINOX arms (93 percent vs 89 percent). [ASCO GI 2018, abstract 348]

This underscores the potential of chemotherapeutic intervention in downstaging nonresectable PDAC, noted the researchers.

Explorative laparotomy was carried out after induction chemotherapy to evaluate for secondary resectability (55 percent vs 48 percent in the GNP and FOLFIRINOX arms, respectively), resulting in a complete macroscopic resection rate of 43 percent and 62 percent, respectively.

The favourable secondary resection rates suggested that GNP-based induction chemotherapy could match the efficacy of FOLFIRINOX as a standard treatment regimen for pancreatic cancer as observed in previous studies, they said. [J Gastrointest Oncol 2017;8:566-571; Cancer Manag Res 2017;9:85-96]

Furthermore, a retrospective study evaluating patients with metastatic pancreatic cancer (median age 69 years, n=31 and 44 on GNP and FOLFIRINOX, respectively) revealed similar progression-free survival (PFS) rates between the two treatment regimens (4.6 and 5.8 months; p=0.523). [ASCO GI 2018, abstract 414]

However, the lower overall survival (OS) rates with GNP vs FOLFIRINOX (6.6 vs 9.2 months; p=0.09) highlighted the need for optimal therapeutic sequencing to prolong OS, the researchers pointed out.

Despite lower discontinuation rates due to grade 3/4 adverse events (AEs, ie, gastrointestinal symptoms, neutropenia, fatigue, and peripheral sensory neuropathy) with GNP vs FOLFIRINOX, the difference was not significant (6.5 percent vs 11.0 percent; p=0.69) as observed in the retrospective trial.

More FOLFIRINOX than GNP recipients progressed to second-line treatment (68 percent vs 32 percent; p=0.0001) and 40 percent of FOLFIRINOX recipients eventually received GNP as second-line treatment, which highlights the efficacy of GNP, noted the researchers.

Another randomized phase II trial further underscored the survival advantage and increased response rate associated with the GNP combination in patients with advanced pancreatic cancer who received either gemcitabine 1,000 mg/m2 alone (n=73) or in combination with NP 125 mg/m2 (n=72). [ASCO GI 2018, abstract 346]

Compared with gemcitabine monotherapy, those who received the GNP combination had a longer OS (9.92 vs 5.95 months, hazard ratio [HR], 0.64, 95 percent confidence interval [CI], 0.42–0.87; p=0.038), median PFS (6.28 vs 3.22 months, HR, 0.58, 95 percent CI, 0.39–0.87; p=0.008), and median time to deterioration (5.36 vs 3.68 months), as well as a higher objective response rate (37.1 percent vs 23.7 percent; p<0.009).

“[These findings suggest that the GNP] combination regimen … is a preferable option for the treatment of patients with advanced pancreatic cancer,” said the researchers.

Taken together, these results add to the growing literature demonstrating the efficacy and tolerability of GNP in pancreatic cancer treatment. [Adv Ther 2016;33:747-759; N Engl J Med 2011;364:1817-1825; N Engl J Med 2013;369:1691-1703]

Nonetheless, researchers of the retrospective study called for randomized trials to further elucidate the potential of GNP as a standard of care for pancreatic cancer.


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