SWOG S1505: Results of perioperative chemotherapy (peri-op CTx) with mfolfirinox versus gemcitabine/nab-paclitaxel (Gem/nabP) for resectable pancreatic ductal adenocarcinoma (PDA).

Abstract

4504 Background: Clinical outcomes after curative treatment of resectable PDA remain suboptimal. To assess the potential of early control of systemic disease with multiagent peri-op CTx, we conducted a prospective trial in the National Clinical Trials Network. Methods: S1505 was a randomized phase II trial of peri-op CTx (12 weeks pre-, 12 weeks post-op) with either mFOLFIRINOX (Arm 1) or Gem/nabP (Arm 2). Eligibility required confirmed tissue diagnosis of PDA, ECOG PS 0 or 1, and resectable disease per Intergroup criteria. Primary outcome was 2-year overall survival (OS), using a “pick the winner” design; for 100 eligible patients (pts), accrual up to 150 pts was planned to account for cases deemed ineligible at central radiology review. We previously presented data on eligibility (ASCO 2019 abstr 4137). Here we present the final efficacy and toxicity results for the eligible pts. Results: From 2015 to 2018, 147 pts were enrolled; there were 102 eligible pts; 55 in Arm 1; 47 in Arm 2. For Arms 1 and 2 respectively: median age, 66 (44-76) and 64 (46-76) years; males, 36 (65%) and 24 (51%); and ECOG PS 0, 34 (62%) and 31 (66%) pts. Treatment details are shown in Table. For Arm 1 and Arm 2, respectively: Two-year OS was 41.6% and 48.8%; median OS was 22.4 months and 23.6 months. Neither arm’s 2-year OS estimate was statistically significantly higher than the a priori threshold of 40% (p=0.42 in Arm 1 and p=0.12 in Arm 2). Median disease-free survival (DFS) after resection was 10.9 months in Arm 1 and 14.2 months in Arm 2 (p=0.87). Conclusions: We have demonstrated: 1) two-year OS of 41.6% (median 22.4 months) with mFOLFIRINOX and 48.8% (median 23.6 months) with Gem/nabP for all eligible pts starting treatment for resectable PDA; 2) post-resection DFS of 10.9 months and 14.2 months, respectively; 3) adequate safety and high resectability rates with peri-op CTx; 4) little evidence that either regimen improves OS compared with the historical standard. Clinical trial information: NCT02562716 . [Table: see text]

Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine

“…72 Interestingly, preliminary results from a randomised phase II SWOG S1505 trial of perioperative m-FOL-FIRINOX versus gemcitabine/nab-paclitaxel in resectable PC, showed similar results in terms of outcomes between the two therapeutic strategies thus indicating that in unselected populations it is almost impossible to see differences between different regimens as well as assess the relative role of platinum compounds versus other agents. 48 It is therefore evident that precision medicine in nonmetastatic PC remains an urgent and unmet need. Tailoring the therapeutic strategy on the molecular profile in preoperative setting is instead fundamental to improving outcome.…”

“…9,13,37,[45][46][47] Additional strategies such as perioperative treatments showed early promising results but need further investigation. 48 Importantly, when preoperative therapy is indicated, current guidelines advice to refer patients to high-volume centres and encourage participation in clinical trials considering the limited evidence to recommend specific neoadjuvant regimens off-study. 39 It is worth highlighting that the aforementioned recommendations on preoperative treatment in non-metastatic PC produced by the most important international cancer societies, are based on systematic reviews of cohort studies (Oxford Levels of Evidence category 2A) due to the lack of large phase III randomised controlled trials conducted in this setting.…”

“… 9 , 13 , 37 , 45 , 46 , 47 Additional strategies such as perioperative treatments showed early promising results but need further investigation. 48 …”

“… 72 Interestingly, preliminary results from a randomised phase II SWOG S1505 trial of perioperative m-FOLFIRINOX versus gemcitabine/nab-paclitaxel in resectable PC, showed similar results in terms of outcomes between the two therapeutic strategies thus indicating that in unselected populations it is almost impossible to see differences between different regimens as well as assess the relative role of platinum compounds versus other agents. 48 …”

Neoadjuvant chemotherapy is associated with improved survival in patients with left‐sided pancreatic adenocarcinoma

“…The NCDB does not capture treatment intent, so it is not possible to determine the number of patients who initiated neoadjuvant therapy but failed to undergo surgical intervention, and this limits our ability to make comparisons to the subset of patients who underwent surgery first. Based on prior single institution studies 16 and the recently published SWOG 1505 trial, 37,38 anywhere from 9% to 25% of patients who start neoadjuvant therapy will not undergo definitive resection. Reasons are multifactorial, including locoregional and distant disease progression as well as toxicity/adverse events that preclude acceptable performance status for major surgery.…”