Stereotactic radiotherapy plus anti PD-1 therapy in patients with locally advanced unresectable pancreatic cancer: Results from a phase 1/2 clinical trial (CA209-9KH).

Abstract

649 Background: The outcomes after the treatment for pancreatic ductal adenocarcinoma (PDAC) are generally disappointing. Except for MSI high tumors, PDAC is considered to be resistant to immune checkpoint inhibitors (ICI). Radiotherapy is thought to be a potential option to foster the effect of ICI. This investigator-initiated trial evaluated safety and efficacy of combining stereotactic radiotherapy (SRT) and ICI. Methods: In this open-label, multicenter phase 1/2 study, patients (pts) aged ≥ 18 years with histologically confirmed locally advanced unresectable PDAC with no distant metastases were enrolled after initial four cycles of induction chemotherapy with FOLFIRINOX. The experimental treatment consisted of SRT (32 Gy in 4 fractions/4 weeks) and sequential nivolumab (N) therapy (3mg/kg every two weeks) administered until disease progression or unacceptable toxicity. After N discontinuation pts could continue treatment with standard chemotherapy regimens. The primary end point was safety (events graded according to NCI CTCAE 4.03 criteria). The secondary objectives were progression free survival (PFS), overall survival (OS), evaluation of selected biomarkers, and quality of life (QoL; EORTC QLQ-C30 questionnaire). The PFS and OS were defined as the time from enrollment to event (i.e., did not include 3-month of ICT and screening). Results: A total of 22 pts. were screened, and 15 pts. were enrolled. Median age was 58 (range 38-74) years, and 53 % were males. All tumors were microsatellite (MS) stable or had unknown MS status. All patients underwent SRT according to the study protocol and all started N. The median number of N cycles was 11 (range 2-17). The toxicity of SRT was low and non-significant. The toxicity of N therapy was expectable. No Grade 4-5 toxicity was observed. Three pts. discontinued therapy because of toxicity (liver test elevation in two cases and unmanageable arthralgia). Median PFS and OS were 8.1 and 13.0 months, resp.; 12-month PFS and OS were 0 % and 66.7%, resp.; and 24-month OS was 8.9 %. The level of selected biomarkers correlated with clinical or radiological disease control. The QoL assessed by pts during the therapy was acceptable, deterioration of QoL in most cases occurred with tumor progression. Conclusions: The toxicity of SRT and N therapy was low and acceptable. There was no unexpected toxicity of combination of SRT of PDAC primary tumor and N, but this regimen did not lead to any long-term treatment responses. Trial registration: EudraCT: 2017-003404-52; ClinicalTrials.gov: NCT04098432. The study was financially supported by Bristol-Meyer-Squibb. Clinical trial information: NCT04098432 .