Search

In patients with unresectable liver metastases from colorectal cancer (CRCLM), systemic doublet or triplet chemotherapy and targeted therapy is considered a standard first-line treatment. Hepatic arterial infusion of oxaliplatin (HAI-ox) generates a high response rate, but this still needs to be confirmed in a randomized trial. We incorporated HAI-ox in doublet or triplet + targeted therapy to validate its efficacy.The OSCAR study is an ongoing randomized phase III trial comparing FOLFOX + targeted therapy according to RAS status, or FOLFOXIRI + bevacizumab in patients eligible for triplet therapy, with the same regimen but with HAI-ox instead of IV-ox as the first-line treatment for CRCLM.Main eligibility criteria are colorectal cancer, unresectable liver metastasis, no extra-hepatic metastases except pulmonary nodules if ≤3 and10 mm, ECOG performance status 0 or 1.The primary endpoint is progression-free survival (PFS). A difference of 4 months for the median PFS in favor of HAI-ox is expected (HR = 0.73). Secondary endpoints include overall survival, overall response rate, secondary liver resection, safety, and quality of life.This study is planned to include 348 patients to demonstrate the superiority of HAI-ox over systemic oxaliplatin in first-line CRCLM treatment (NCT02885753).

Background Chemotherapy is effective in metastatic pancreatic adenocarcinoma (mPA), but new approaches are still needed to improve patients' survival and quality of life. We have previously published good efficacy and tolerability results on a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI (5FU+irinotecan) regimen. In the present study, we evaluated the same sequence but replaced gemcitabine by the new gemcitabine + nab-paclitaxel standard first-line combination. Patients and methods We randomised chemotherapy-naive patients with proven mPA, bilirubin levels ≤1.5 upper limit of normal values and performance status 0–2 to alternately receive gemcitabine + nab-paclitaxel for 2 months then FOLFIRI.3 for 2 months in arm A, or gemcitabine + nab-paclitaxel alone until progression in arm B. The primary objective was to increase the 6-month progression-free survival (PFS) rate from 40% (H0) to 60% (H1); using the binomial exact method, 124 patients were required. Analyses were carried out in preplanned modified intention-to-treat (mITT) and per-protocol (PP) populations. Results Between November 2015 and November 2016, 127 patients were enrolled. Main grade III–IV toxicities (% in arm A/B) were: diarrhoea (12.5/1.7), neutropenia (46.9/31, including febrile neutropenia: 1.6/0), skin toxicity (6.3/13.8), and peripheral neuropathy (6.3/8.6). No toxic deaths occurred. The objective response rate was 40.3% (95% confidence interval [CI]: 28.1–53.6) in arm A and 26.7% (95% CI: 16.1–39.7) in arm B. The primary end-point (6-month PFS rate) was 45.2% [one-sided 95% CI: 34.3–56.4] in arm A and 23.3% in arm B [one-sided 95% CI: 14.3–32.3] in the mITT population. In the PP population, median PFS and OS were 7.6 months and 6 months and 14.5 months and 12.2 months in arm A and B, respectively. Conclusions The FIRGEMAX strategy with gemcitabine + nab-paclitaxel alternating with FOLFIRI.3 every 2 months, appears feasible and effective, with manageable toxicities, in patients able to reach >2mo of treatment. Trial registration information EudraCT: 2014-004449-28: NCT: 0282701.

387 Background: Several options have been evaluated as 2nd line treatment in mGA after failure of 1st line platinum based chemotherapy including taxanes and IRI as monotherapies or paclitaxel combined with ramucirumab but with a limited efficacy. REG monotherapy showed promising efficacy as 2nd or 3rd line treatment in mGA (Pavlakis N et al, J Clin Oncol. 2016). Methods: This comparative phase 2 multicenter randomized study was designed to evaluate the safety and efficacy of REG + IRI (REGIRI) vs IRI alone as 2nd line treatment in MGA patients (pts). Key eligibility criteria were histologically proven mGA (gastric or gastroesophageal junction (GEJ) tumor Siewert II and III), fluoropyrimidine and platinum-based first-line chemotherapy and ECOG PS ≤1. Pts received IRI 180 mg/m2 IV on D1 and D15. In REGIRI arm REG 160 mg/day was added on D2-D8 and D16-D22 every 28 days. Primary endpoint was overall survival (OS). A total of 122 events (154 pts) were required based on an assumption of 4-month (mo) gain in median OS (from 6 to 10 mo, HR=0.60), with a preplanned interim analysis of safety after 38 pts and efficacy after 40 OS events. Genotyping of cyclin-D1 was performed to evaluate the impact of treatment efficacy. Results: A total of 89 patients (REGIRI, n=44; IRI, n=45) with median age of 62 (range: 28-82) years and a mGA (67.4% with GEJ, 22.8% HER2+) were included out of the 154 initially planned by 21 sites in France. Study was prematurely stopped after interim analysis for unfavourable efficacy/toxicity ratio. With a median follow-up of 19.4 mo, 79 OS events were observed and median OS was 6.3 mo (95%CI[5.2-7.1]) with REGIRI vs 8.2 mo (95%CI[5.2-9.7]) with IRI (HR=1.11 CI95%[0.70-1.74], p=0.66). Median PFS was 2.2 mo vs 1.9 mo (NS) with REGIRI and IRI, respectively. Objective response rate was 15.9% and 13.3% respectively. Disease control rate was 45.5% and 33.3%. AEs grade ≥ 3 related to treatment were reported in 52.3% of pts in REGIRI arm vs 23.3% in IRI arm with 4 toxic deaths (diarrhea, sepsis and thromboembolic events) vs 1 (primary tumour perforation), respectively. The main severe toxicities were diarrhea: 18.2% vs 7% and febrile neutropenia: 8.2% vs 0%. Genotyping of cyclin D1 was performed on 72 pts: 19 presented A/A genotype, 38 A/G and 15 G/G. There were no differences in terms of OS according to genotyping. Conclusions: PRODIGE58/REGIRI trial was prematurely stopped after the interim analysis due to high toxicities reported in REGIRI arm with negative results on its primary endpoint. Further ancillary analysis are expected to identify toxicity risk factors and pts subgroups benefit with this combination. Clinical trial information: NCT03722108 .

92 Background: Adjuvant chemotherapy is the current worldwide standard of care for stage III colorectal cancer (CRC) but it leads to significant neurotoxicity. We have shown in 2 cohorts of CRC patients treated with Oxaliplatin (Ox) that Ox-due neuropathy occurred in patients receiving an excess of 3.09 mg Ox/ kg Lean Body Mass (LBM). The aim of this trial was to determine whether the Ox dose adaptation based on the LBM index can reduce neurotoxicity, in patients treated for a stage III CRC. Methods: LEANOX is a randomized phase II multicentre study in patients eligible for an Ox regimen as adjuvant chemotherapy for CRC. Patients without sarcopenia (LBM index

Background Patients with gastrointestinal (GI) cancer are exposed to cachexia, which is highly correlated with chemotherapy-induced side effects. Research suggests that specific immunonutrients could prevent such toxicities. Aims The primary objective of this phase III study was to evaluate the efficacy of glutamine and transforming growth factor-β2 (TGF-β2) in the prevention of grade 3–4 non-hematological toxicities induced by chemotherapy in patients with GI cancer. Patients and methods We designed a double-blind, randomized, controlled and multicenter trial stratified according to center, type of chemotherapy, presence of cachexia, and age. Patients were randomized to receive either Clinutren Protect® (CP) or a control isocaloric diet (without TGF-β2 or glutamine). Results Between November 2007 and October 2011, 210 patients were enrolled in the study, of which 201 were included in the intention-to-treat analysis. Grade 3–4 non-hematological toxicities were not significantly different between the CP and control groups when evaluated by univariate and multivariate analyses. Likewise, no difference was observed regarding grade 3–4 hematological toxicities or reasons for treatment interruption. Conclusion This randomized study does not support the hypothesis that oral glutamine and TGF-β2 supplementation is effective to reduce grade 3 or 4 non-hematological toxicities induced by chemotherapy in patients with GI neoplasm.