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

Flavio G. Rocha, MD—Chair, Virginia Mason Hospital and Medical Center

Mario Strazzabosco, MD, PhD—Chair, Yale School of Medicine

Abstract 186: Analysis of survival and objective response (OR) in patients with hepatocellular carcinoma in a phase III study of lenvatinib (REFLECT).
First Author: Masatoshi Kudo, MD, PhD

Conclusions:

Objective response by mRECIST was an independent predictor of OS in patients with HCC regardless of treatment

  - The association between OR by mRECIST and OS was consistent with results reported in the previous studies1-3

  - Additional predictors of OS include MVI, baseline AFP level, number of tumor sites, involved tumor site (liver), at least 1 prior procedure for HCC, and treatment 

Therefore, patients who achieve an objective response can potentially expect a langer OS. However, additional studies are needed to further validate the correlation between OR and OS 

Clinical trial information: NCT01761266

Abstract 189: Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP-05).
First Author: Michiaki Unno, MD, PhD

Conclusions:

  • The median OS was 36.72 months in NAC-GS group as compared with 26.65 months in Up-S group (HR for death, 0.72, 95%CI 0.55-0.94, p=0.015).
  • Grade 3 or 4 adverse events frequently (72.8%) observed in NAC-GS were leukopenia or neutropenia. However, NAC-GS was safe and  feasible.
  • Lymph node metastasis was significantly decreased in NAC-GS group (59.6% vs 81.5%)

This phase III study demonstrated the significant survival benefits of NAC-GS treatment. Therefore, the results indicated that neoadjuvant chemotherapy could be a new standard for patients with resectable PDAC. Clinical trial information: UMIN000009634.

Andrew X. Zhu, MD, PhD
Harvard Medical School, Massachusetts General Hospital Cancer Center
Discussion

Abstract 187: Efficacy and safety of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E–mutated biliary tract cancer (BTC): a cohort of the ROAR basket trial.
First Author: Zev A. Wainberg, MD

Conclusions:

  • These results represent the first prospectively analyzed cohort of patients with BRAF V600-mutant BTC treated with a combination of BRAF and MEK inhibitors
  • Efficacy in this population with advanced disease was comparable to that of first-line chemotherapy with gemcitabine + cisplatin

  - lnvestigator-assessed ORR was 42%, median PFS was 9.2 months (95°/o Cl, 5.4-10.1 months), and median OS was  11.7   months (95% Cl, 7.5-17.7 months)

  • Molecular analyses demonstrated heterogeneous genetic backgrounds of BTC tumors and low mutational burden, consistent with other reports in this tumor type

 - Two patients with BOR of PD had the highest expression of MAPK pathway genes of all cases analyzed; additional study  is   needed to confirm any association with clinical benefit

  • Dabrafenib + trametinib demonstrated clinical benefit in patients with BRAF-mutant BTC and should be considered a meaningful therapeutic option for these patients
  • BRAFV600 is an actionable driver mutation and should be considered for routine testin in patients with BTC

Clinical trial information: NCT02034110

Abstract 188: Integrative molecular profiling and response to chemotherapy on the COMPASS trial.
First Author: Grainne M. O'Kane, MB BCh BAO MRCPI, MD 

Conclusions:

 
  • Achieving WGS and RNAseq in met PDAC is feasible

         -        Highly actionable variants detected (many platforms)

         -        COMPASS provides a rich discovery set for other hypotheses and collaborators (EPPIC and ICGC ARGO and others)

  • modMoffitt and GATA6 discriminate two prognostic groups:

         -        The basal-like cohort (GATA6 low) may be particularly resistant to mFF

         -        Validation in prospective trials to determine GATA6 (other markers) as predictive biomarkers and discover more    

                  optimal therapies

Subsets of pts with advanced PDAC have actionable variants including those with HRD signatures and patients with KRAS WT tumors. GATA6 is a putative predictive biomarker of transcriptomic subgroups which should be incorporated in clinical trials. Clinical trial information: NCT02750657

Heinz-Josef Lenz, MD
University of Southern California
Discussion