Prognostic effect of primary tumor location in the NAPOLI-1 phase 3 study in metastatic pancreatic ductal adenocarcinoma (mPDAC) (2018)

Introduction: In NAPOLI-1 (NCT01494506), treatment with liposomal irinotecan + 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) significantly increased median overall survival (mOS) vs. 5-FU/LV (6.1 vs. 4.2 months; unstratified hazard ratio [HR]=0.67, 95% confidence interval [CI]:0.49–0.92; P = 0.012) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who had progressed following gemcitabine-based therapy. A potential prognostic impact of primary tumor location on metastatic pancreatic cancer outcomes has been reported. We investigated the effect of primary tumor location on survival following inclusion in the NAPOLI-1 study. Methods: This post-hoc analysis explored outcomes in patients with primary tumor locations of the pancreatic head only (H only), body only (B only), tail only (T only), and multiple locations including (H_incl) and excluding (H_excl) the head. Results: Of 417 patients, 239 (57%) had a primary tumor location of H only, 54 (13%) B only, 62 (15%) T only, 17 (4%) H_incl and 30 (7%) H_excl. Karnofsky performance status was lower in patients with a primary tumor location of T only versus the intent-to-treat population. The mOS (HRs: 0.87–1.06) and median progression-free survival (mPFS) (HRs: 0.82–0.98) were similar across primary tumor location subgroups and no clear prognostic signal for OS was detected. The mOS and mPFS in patients with a primary tumor location of H only were 5.0 and 2.7 months, respectively, versus 5.4 and 2.8 months, respectively, for those with B only (mOS: HR = 1.06, 95%CI:0.75–1.50, P = 0.737; mPFS: HR = 0.98, 95%CI:0.70–1.37, P = 0.925). For patients with T only, mOS and mPFS were 4.3 and 1.7 months respectively (mOS H only vs. T only: HR = 0.89, 95%CI:0.64–1.23, P = 0.469; mPFS H only vs. T only HR = 0.89, 95%CI:0.66–1.22, P = 0.471). For patients with H_incl, mOS and mPFS were 5.7 and 2.3 months respectively, while for H_excl patients they were 4.6 and 1.4 months, respectively. For the comparison of mOS between the H only and B only+T only+H_excl subgroup (mOS=4.4, mPFS=1.7 months), HR = 0.88 (95%CI:0.69–1.11, P = 0.285) while for mPFS HR = 0.83 (95%CI:0.66–1.05, P = 0.116). For the comparison of mOS between the H only and B only+T only+H_excl+H_incl subgroup (mOS=4.6, mPFS=1.7 months), HR = 0.91 (95%CI:0.72–1.15, P = 0.421), while for mPFS HR = 0.87 (95%CI:0.70–1.09, P = 0.233). For the comparison of mOS between the H only+H_incl and B only+T only+H_excl subgroup HR = 0.87 (95%CI:0.69–1.10, P = 0.240), while for mPFS HR = 0.82 (95%CI:0.65–1.03, P = 0.084). Both mOS and mPFS were higher in patients treated with nal IRI+5 FU/LV vs. 5 FU/LV across primary tumor location subgroups (mOS: HRs: 0.39–0.88; two groups with n < 10 per arm were discounted). Safety, drug related AEs and dose modifications/discontinuations in the PTL subgroups were broadly similar to the overall NAPOLI 1 study arms. Conclusion: In NAPOLI-1, 61% of patients had a primary tumor location including the pancreatic head. This analysis did not detect a clear prognostic effect of primary tumor location on survival for mPDAC patients progressing after gemcitabine-based treatment. Patients with primary tumors in the head only or including head had similar mOS and mPFS to other patients. A consistent treatment benefit was shown with nal-IRI+5-FU/LV vs. 5-FU/LV regardless of primary tumor location.