Rapid Abstract Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Philip A. Philip, MD, PhD, FRCP—Chair, Karmanos Cancer Institute, Wayne State University

Shailesh V. Shrikhande, MD, MS, FRCS—Chair, Tata Memorial Hospital

Abstract 185: Randomized, open-label, perioperative phase II study evaluating nivolumab alone versus nivolumab plus ipilimumab in patients with resectable HCC.
First Author: Ahmed Omar Kaseb, MD

Conclusions:

We report a pCR rate of 37.5% (3/8 cases) in the first interim analysis of a phase II pilot trial of perioperative immunotherapy for resectable HCC. Treatment was deemed safe and surgical resection was not delayed. pCR was associated with a significant increase in two clusters of CD8 T-Cell and in Teff/Treg ratio after therapy. The study is ongoing and results may contribute to a paradigm shift in the perioperative treatment of HCC. Clinical trial information: NCT03222076

Abstract 190: Pembrolizumab treatment of advanced neuroendocrine tumors: Results from the phase II KEYNOTE-158 study.
First Author: Jonathan R. Strosberg, MD

Conclusions:

Data from 107 patients with previously treated NET enrolled in KEYNOTE-158 showed an ORR of 3.7%, including no complete responses and 4 partial responses (3 pancreatic and 1 gastrointestinal <unknown primary>).

Responses were durable, with a median duration of response that had not been reached (range 4.1-15.9+), and 3 of 4 responses ongoing after ≥9 months.

The safety profile was consistent with that previously observed for pembrolizumab in patients with advanced cancer

Clinical trial information: NCT02628067

Abstract 191: Outcomes in pancreatic adenocarcinoma (PDA) patients (pts) with genetic alterations in DNA damage repair (DDR) pathways: Results from the Know Your Tumor (KYT) program.
First Author: Michael J. Pishvaian, MD, PhD

Conclusions:

1. In the absence of platinum-based therapy, there is no increase in OS observed in HA-DDR mutated vs. HA-DDR proficient patients 
  - This suggests that HR-DDR deficiencies are not likely prognostic 
2. But, advanced patients with HR-DDR mutations have an improved OS when treated with platinums, compared to HR-DDR proficient patients 
  - ~50% of patients are treated with a NON-platinum-based 1st line regimen 
  - And only ~50% of patients are exposed to any 2nd line therapy 
  - As high as 75% ot HR-DDR mutated patients might not be getting "optimal" therapy 
3.    Prospective studies that incorporate molecular testing are warranted 
  - Germline testing of ALL pancreatic cancer patients is now NCCN-guideline recommended 
  - Should platinum-based therapy be prioritized for all HR-DDR mutations? 
4.    Additional patient enrollment will be critical to understanding the prognostic and predictive role cf other HA-DDR subgroups 
  - And response to PARP/ATR/ATM and other DDR Inhibitors 



Abstract 192: Immune checkpoint inhibition (ICI) in combination with SBRT in patients with advanced pancreatic adenocarcinoma (aPDAC).
First Author: Gagandeep Brar, MD

Conclusions:

The combination of ICI and SBRT is safe and well tolerated in patients with aPDAC.

With a median follow-up of 3.4 months, the median PFS was 2.2 months and median OS was 4.9 months

- Durable responses were observed in 2 patients lasting over 12 months
- 5 Gy x 5 +Durvalumab/Tremelimumab combination

The overall response rate of 9.6% including 2 patients who achieved a durable partial response lasting over 12 months, suggests meaningful clinical activity. This signifies that ICI and SBRT is a potential new treatment for aPDAC. Clinical trial information: NCT02311361