Perioperative chemotherapy for resectable pancreatic ductal adenocarcinoma

The phase 2 SWOG S1505 study, evaluating the efficacy and safety of 2 perioperative chemotherapy regimens, failed to reach its primary endpoint as overall survival (OS) at 2 years did not exceed the prespecified threshold.

Dissection followed by adjuvant chemotherapy remains the standard-of-care for resectable pancreatic cancer. However, outcomes remain suboptimal, due to the inability of many patients to receive adjuvant chemotherapy as well as early progression in the perioperative period. Perioperative chemotherapy using aggressive multi-agent chemotherapy regimens for early control of systemic disease could overcome these problems.

Key eligibility criteria for SWOG S1505, designed to evaluate efficacy and safety of both modified FOLFIRINOX and gemcitabine plus nab-paclitaxel, included a confirmed tissue diagnosis of pancreatic adenocarcinoma [1]. No prior cancer therapy of any kind was allowed. Resectability was strictly defined, using a contrast-enhanced CT or MRI. Patients were randomised in a 1:1 ratio to either modified FOLFIRINOX (5FU 2,400 mg/m², irinotecan 180 mg/m², oxaliplatin 85 mg/m²) or gemcitabine (1,000 mg/m²) plus nab-paclitaxel (125 mg/m²).

The preoperative portion was 3 months of chemotherapy following which a restaging scan was performed. In the absence of progressive disease, surgical dissection was performed. After dissection, patients were assigned to 3 more months of chemotherapy with the same regimen that they were randomised to originally for a total of 6 months of perioperative chemotherapy. Primary endpoint of SWOG S1505 was OS at 2 years. The study had a "pick the winner" design in which OS at 2 years for each arm was compared with the historical threshold of 40%. If 2-year OS reached 58% or more, the 2 arms would be compared for superiority.

A total of 147 patients were enrolled, but 43 patients had ineligible disease by a central radiology review. Of all eligible patients, 53 actually started preoperative modified FOLFIRINOX and 45 started preoperative gemcitabine/nab-paclitaxel. Respectively, 31 and 26 patients started postoperative chemotherapy; 27 and 19 patients completed postoperative chemotherapy.

The study did not meet its primary endpoint: 2-year OS was 43.1% in the modified FOLFIRINOX arm and 46.9% in the gemcitabine/nab-paclitaxel arm. Median OS was 22.4 months and 23.6 months, respectively. Complete major response was achieved in 25% of the patients in the modified FOLFIRINOX arm and in 42% of the patients in the gemcitabine/nab-paclitaxel arm. R0 resection was achieved in 85% of the patients in both arms. Median disease-free survival after resection was 10.9 months in the modified FOLFIRINOX arm versus 14.2 months in the gemcitabine/nab-paclitaxel arm.

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   1. Sohal D, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract 4504

Posted on 17 September 202019 September 2020