Session I: Cancer of the Pancreas and Biliary Tract



Late-Breaking Abstract-1: First-line liposomal irinotecan + 5 fluorouracil/leucovorin + oxaliplatin in patients with pancreatic ductal adenocarcinoma: primary analysis from a phase 1/2 study

The authors conclude, that the findings from this phase 1/2 study suggest that NALIRIFOX is tolerable for patients with previously untreated locally advanced mPDAC. There were no new safety signals detected and the antitumor activity (secondary outcome) was promising. The median PFS was 9.2 months (95% CI: 7.69-11.96) and the median OS was 12.6 months (95% CI: 8.74-11.69). The authors observed antitumor activity which warrants further investigation. Efficacy is the primary objective of the ongoing NAPOLI-3 phase 3 study in adults with previously untreated mPDAC.


Late-Breaking Abstract-2: Two arm randomized prospective superiority Phase II multicentric clinical trial to evaluate the efficacy of capecitabine-irinotecan (CAPIRI) versus Irinotecan in advanced gall bladder cancer progressing on first line chemotherapy

The authors conclude that monotherapy with irinotecan is as efficacious as combination chemotherapy (CT) with CAPIRI as 2nd-line therapy in advanced GBCs (PFS & OS). They observed responses with combination CT, but CBR are similar to an increased rate of grade 3/4 side-effects. The combination CT entails significant dose modifications, hampering the administration of treatment in these fragile pts, and thereby contributing to a lack of efficacy. In conclusion: Monotherapy with irinotecan is a reasonable 2nd-line option and irinotecan is a comparator regimen in future trials.


Short Oral-1: Prognostic nomogram to predict overall survival in patients with unresectable pancreatic cancer treated with gemcitabine plus nab-paclitaxel or FOLFIRINOX: Real-world results from the multicenter retrospective study (NAPOLEON study).

The authors developed a convenient prognostic nomogram based on five independent prognostic factors (ECOG PS, liver metastasis, LDH, CRP & CA19-9). They verified the nomogram using C-index t-AUC, calibration plot, and Kaplan-Meier curve divided into three risk stratification. They conclude, that their prognostic nomogram can accurately and conveniently predict prognosis in patients with unresectable PC treated with GnP or FFX.


Short Oral-2: Prevalence and prognostic role of inherited germline mutations in cancer predisposing genes in unselected patients with pancreatic cancer.

The authors conclude that a significant proportion of unselected patients with PDAC carry clinically relevant germline PVs irrespective of age, family history, or disease stage. The observed, that the presence of PVs was not independently associated with improved OS and they did not observe a benefit by the administration of platinum-based therapy in pts with HRR PVs in terms of OS. They suggest that the validation of the prognostic and predictive significance of PVs through universal genetic testing of pts with PDAC (newer treatments) is critical.

Short Oral-3: Maintenance olaparib in patients aged ≥65 years with a germline BRCA mutation and metastatic pancreatic cancer: Phase III POLO trial

The authors conclude that in the phase 3 POLO trial, patient age did not appear to have an impact on the efficacy of maintenance olaparib (subgroups were small). As in the overall population, no baseline characteristics were predictive of olaparib response in pts aged ≥65 years. The safety & tolerability profiles of olaparib were consistent between the ≥65 and <65 year age groups. They conclude further that pts aged ≥65 years with gBRCAm and metastatic pancreatic cancer can derive durable disease control (≥2 years) and tumor response from maintenance olaparib treatment.


Short Oral-4: Phase Ib/II, open-label, randomised evaluation of atezolizumab plus RO6874281 vs control in MORPHEUS–pancreatic ductal adenocarcinoma (PDAC)

The authors conclude that[nbsp]limited responses were observed in the atezolizumab + RO6874281 (Simlukafusp alfa) arm in comparison with chemotherapy (CT) control in 2L (in 2L, one PR was observed in a pt with MSI-H tumor with DOR of 7.4 months. In 3L, on PR was observed in a pt with MSS tumor with DOR of 5.6 months. This pt received a different atezolizumab combination in 2L. The mOS of 2L atezolizumab + RO6874281 Q2W (chemo free) of 7.3 months is comparable to the chemo control arm's mOS of 7 months. The mOS of 3L atezolizumab + RO6874281 Q3W was 6.8 months.

The authors observed that the atezolizumab + RO6874281 Q3W & Q2W regimen was well tolerated, and no new safety signals were identified. In conclusion, pancreatic cancer response to checkpoint inhibitors (CPIs) is historically low, and the addition of RO6874281 to atezolizumab did not increase the response rate in this signal-seeking study. To enhance responses to CPIs in pancreatic cancer, further exploration of novel combinations is warranted.


Short Oral-5: Efficacy of second-line chemotherapy in patients with advanced or metastatic cholangiocarcinoma and FGFR2 fusions: A retrospective analysis.

The authors conclude that Infigratinib is an oral, FGFR1-3-selective TKI that shows meaningful clinical activity against chemotherapy (CT)-refractory CCA containing FGFR2 fusions, with confirmed ORR of 26.9% (95% CI 16.8-39.1) and DOR of 5.4 months (95% CI 3.7-7.4). The limitation of this retrospective study is the reliance upon investigator assessment of medical history for retroactive adjudication or response or progression on prior standard 2nd-line CT in pts with CCA and FGFR2 fusions.

The authors nevertheless conclude that these retrospectively analyzed outcomes from 2nd-line CT in pts wit CCA and FGFR2 fusions were similar to those reported in the literature for all pts with CCA regardless of genomic status and remain dismal. Infigratinib administered as 3rd- and later-line treatment resulted in a meaningful PFS and ORR benefit in pts with CCA and FGFR2 fusions.


Oral-1: PanCO: Updated results of an open-Label, single-arm pilot study of oncoSil phosphorus-32 microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine + nab-paclitaxel or FOLFIRINOX chemotherapy

The authors conclude that the use of EUS-guided 32p implantation is feasible, with an acceptable safety profile in combination with 1st-line SoC chemotherapy (CT) for LAPC over a prolonged study timeframe. The observed that relatively few AEs were attributed to the OncoSilTM device and/or implantation procedure compared to CT. They further conclude that at a relatively mature follow-up (median 16.1 months), the PanCo study results provide a consistent set of outcomes that suggest clinically relevant benefits for pts with unresectable LAPC treated using OncoSilTM device together with systemic CT. They observed encouraging clinical efficacy outcomes, particularly tumor response, surgical resection with curative intent, PFS & OS. Further clinical studies on OncoSilTM are developing.


Oral-3: Efficacy and safety of entrectinib in NTRK fusion-positive gastrointestinal cancers: updated integrated analysis of three clinical trials (STARTRK-2, STARTRK-1 and ALKA-372-001)

The authors conclude that in this updated integrated analyses of three phase 1/2 clinical trials, entrectinib continued to induce clinically meaningful, durable systemic responses in pts with a range of NTRK fusion-positive gastrointestinal carcinomas (ORR: 50%; median DOR: 12.9 months; median PFS: 7.1 months). Entrectinib was well tolerated and most AEs were managed with dose interruption/reduction and the discontinuation rate was low. The authors finally conclude that the efficacy data should encourage broader NTRK screening of pts wit gastrointestinal cancers, as they may benefit from entrectinib.


Oral-4: NTRK gene fusions in bilio-pancreatic cancers.

The authors conclude that consistent with the low frequency in solid tumors, NTKR gene fusions are also rare in bilio-pancreatic cancers. They maintain testing and identification are of high clinical importance (using a 2 step-diagnosis: RNA-based NGS to confirm positive pan-TRK IHC - economic & time impact. Possible treatment with specific pan-TRK inhibitors - marked & durable responses). There is an interest of both known and unknown genomic fusions partners (comparison between Archer platform vs Oncomine).


P-48 First evidence for the antitumor activity of nanoliposomal irinotecan in metastatic biliary tract cancer (on page s105)

The authors conclude that this retrospective analysis provides the first evidence that Nal-IRI might exhibit a clinical meaningful antitumor activity in metastatic biliary tract cancer by controlling the disease.