Background: Palliative care (PC) is integrated into standard oncology care. However, its clinical impact at the end of life remains unclear in pancreatic adenocarcinoma (PA). We aimed to describe the end-of-life care pathway and to assess whether PC referral influences survival after chemotherapy discontinuation (CD) among advanced PA patients.Methods: This retrospective single-centre observational study was conducted among deceased patients with advanced PA who had received chemotherapy between January 1, 2016, and December 31, 2021. Baseline characteristics, the timing of PC referral and events after CD were collected. The primary outcome was time from CD to death.Results: Among the 148 included patients, 53.4% (n = 79) received PC, mostly late after the CD (n = 133, 89.9%), 16.9% (n = 25) received chemotherapy in the last 14 days of life and 75.6% died at the hospital. None received PC in the 8 weeks following the diagnosis. PC referral significantly increased PC department admissions (p < 0.001) and decreased medical unit admissions (p < 0.001). The median survival after the CD was 35 days (IQR: 19-64.5). PC referral was associated with increased survival after CD (HR: 0.65 [0.47-0.90], p = 0.010, Cox) and after adjusting (HR: 0.65 [0.42-0.99], p = 0.045, Cox). Conclusion: The study suggests that PC may be associated with longer survival after CD in advanced PA patients. However, PC is underused, and patients are referred late in their care pathway.& COPY; 2023 Published by Elsevier B.V. on behalf of IAP and EPC.

Cell-free DNA (cfDNA) analysis has shown promising results for the management of patients with cancer, but few data exist in patients with metastatic gastro-esophageal adenocarcinomas (mGEA). In this study, we analyzed cfDNA extracted from blood of patients included in the REGIRI - PRODIGE 58 trial (Regorafenib + irinotecan as 2nd line in patients with mGEA). 239 samples from 34 patients with mGEA included in the Regiri arm were available for analysis. Plasma samples were taken before treatment's initiation, then at days 1, 2, 8 and 15 of Cycle 1 and days 1, 8 and 15 of Cycle 2. cfDNA was extracted from plasma, concentrations and fragments sizes determined by fragment analysis. First and last time points were selected to estimate concentration's evolution for each patient. A cfDNA threshold concentration (tc) of 0.55 ng/μL was settled as the best threshold at baseline to separate patients into 2 groups "low" and "high" corresponding to concentrations lower or greater than tc respectively. Among the 34 patients analyzed, 1 patient was excluded because of genomic DNA contamination in plasma at baseline. 16 patients (48.48%) were in the "low" group and 17 (51.52%) in the "high" group. For cfDNA concentration at baseline and PFS, a trend non-statistically significant difference (HR=0.53; CI95[0.2595;1.085]; p=0.0564) was found: Low cfDNA concentration at baseline was associated with a better PFS (2.6 vs 1.7 months). 4 distinct subgroups emerged: Patients with low concentration at baseline that remains low (low-low), low at baseline with an increase during follow-up (low-high), high at baseline with a decrease during follow-up (high-low) and high at baseline that remains high (high-high). A statistically significant difference was found for PFS (4.55 vs 2.11 months) between the low-low and high-high subgroups respectively (HR=0.4139; CI95[0.1652;1.037]; p=0.022). Our findings suggest that cfDNA concentration at baseline and cfDNA clearance might have an interest to predict PFS in patients with mGEA. Further investigations are ongoing to decipher if genomic signatures can be predictive of PFS in patients with mGEA.

For shrinkage of RAS/BRAF WT tumors, anti-EGFR antibodies combinated with triplet chemotherapy (CT) regimen have shown promising results in phase I-II trials. Ultrasensitive cirDNA analysis as those with IntPlex® technology might result in better selection of super-responders to anti-EGFR-based therapies. Thus, the aim of PANIRINOX was studying the complete response (CR) rate obtained with P plus a tri-CT regimen (FOLFIRINOX = Arm A) or a standard bi-CT (mFOLFOX6 = Arm B) in pts with cirDNA-based RAS/BRAF V600E WT unresectable mCRC tumors.

The perioperative FLOT triplet chemotherapy regimen is the standard of care for localized gastric and GEJ adenocarcinomas. We explored the superiority of a modified FLOT (mFLOT=TFOX regimen) vs FOLFOX in patients with advanced disease.

No clinical trial has evaluated the benefit of 2d-line chemotherapy in metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) after FOLFIRINOX (FFX) failure. In this randomized phase 3 trial, pts were assigned in a 2:1 ratio to either receive GEMPAX (gemcitabine 1000mg/m2 + paclitaxel 80mg/m2 IV infusion at D1, 8 and 15 every 28 days) (arm A/experimental) or GEM (gemcitabine alone) (arm B/control) regimen after failure or intolerance to 1st-line FFX regimen. Primary endpoint was overall survival (OS). Secondary endpoints included Progression-Free Survival (PFS), Objective Response Rate (ORR) and safety. From June 2019 to March 2021, 211 pts were randomised (140 in arm A/71 in arm B) in 31 French centers. Median age was 64 years (30-86), 62% were male, ECOG-PS 0-1 88%. Tumor location in the pancreas was head (33%) tail (25%) or body (22%). 76% pts were metastatic at diagnosis. Median follow-up was 6.3 vs 5.9 mo in arm A vs arm B. At data cut-off, median OS (95%CI) was 6.4 (5.2-7.4) vs 5.9 mo (4.6-6.9) in arm A vs arm B (HR=0.87 [0.63-1.20]; p=0.4095), median PFS 3.1 (2.2-4.3) vs 2.0 mo (1.9-2.3) (HR=0.64 [0.47-0.89]; p=0.0067), and ORR 19% (13-27) vs 5% (1-13%) (p=0.008). Overall, 17% pts in arm A and 3% in arm B discontinued their treatment due to treatment-related adverse events (TRAEs). Grade (G) 3/4 TRAEs were reported in 58% vs 27% in arm A vs arm B among which 15% vs 4% anaemia, 16% vs 16% neutropenia, 20% vs 4% thrombocytopenia, 10% vs 3% asthenia and 12% vs 0% neuropathy. Only one G 5 TRAE was reported in arm A (acute respiratory distress). Noticeably, 32% (arm A) vs 47% (arm B) pts received 3rd-line therapy including taxanes (2% vs 23%), platinum salts (9% vs 10%) or irinotecan (9% vs 1%). The combination of paclitaxel + gem brought no benefit in OS over gem alone to mPDAC pts in 2nd-line setting but significantly improved both PFS and ORR. Imbalance in 3rd line therapies and notably the use of taxanes in gem monotherapy arm might explain the lack of benefit in OS. Altogether, these results highlight the medical need for new therapeutic options for pre-treated mPDAC pts.

Background Previous studies have observed an increased incidence of Cetuximab-induced hypersensitivity infusion reactions (CI-IRs) in the southeastern states of the USA. Tick’s bites were suspected of generating cross-reactions between cetuximab and alpha-gal. This study aims was to describe the incidence and associated risk factors of CI-IRs, in the French areas chosen according to their Lyme disease incidence. Patients and methods A retrospective chart review was conducted on patients that received cetuximab infusion from January 2010 to June 2019 in 4 French areas with different Lyme disease incidence rates. Results Of 1392 patients, 117 (8.4%) experienced a CI-IR, including 68 severe (grade 3 or 4) reactions (4.9%). This CI-IR incidence was significantly higher in the Lyme disease high-risk area than in the other areas (13.2% versus 7.1%, 8.1% and 6.4%; P=0.016). Sex (P=0.53), premedication (P=0.91), primary cancer location (P=0.46) and chemotherapy regimen type (P=0.78) had no impact on CI-IR incidence in the overall population. In the head and neck squamous cell carcinoma (HNSCC) patient subgroup, CI-IRs were significantly more frequent in the high-risk area (16.4% versus 6.7%, 7.1% and 7.0%; P=0.0015). Conclusion This study suggests that patients treated in the French area with the highest incidence of Lyme disease are at a higher risk of CI-IRs.

Background: The COVID-19 pandemic led to a significant reduction in the provision of screening, case identification and hospital referrals to cancer patients. To our knowledge, no study has yet correlated quantitatively the consequences of these limitations for cancer patient management. This study evaluates the implications of such reductions for patients newly diagnosed with metastatic colorectal cancer (mCRC) in both the pre- and post-lockdown periods. Methods: We examined 80 newly identified mCRC patients from 18 different clinical centers. These cases come from the screening procedure of a clinical trial which is using circulating DNA (cirDNA) analysis to determine their RAS and BRAF status. Results: The tumor burden as evaluated by the median total plasma cirDNA concentration showed a statistically higher level in patients diagnosed post-lockdown compared to those diagnosed pre-lockdown (119.2 versus 17.3 ng/mL; p<0.0001). In order to link tumor burden to survival, we compared the survival of these mCRC patients with previous studies in which cirDNA was examined in the same way (median survival, 16.2 months; median follow up, 48.7 months, N=135). Given the poor survival rate of mCRC patients with high cirDNA levels (14.7 vs 20.0 and 8.8 vs 19.3 months median survival when dichotomizing the cohort by the median cirDNA concentration 24.4 and 100 ng/mL, respectively), our study points to the potential deleterious consequences of the COVID-19 pandemic. Conclusions: Recognizing that our exploratory study offers a snapshot of an evolving situation, our observations nonetheless clearly highlight the need to determine actions which would minimize delays in diagnosis during the ongoing and future waves of COVID-19.

First-line treatment for mCRC pts consists of a fluoropyrimidine-based chemotherapy (5-FU or capecitabine combined with oxaliplatin and/or irinotecan) with VEGF or EGFR inhibitors. Once these treatment options have been used, or are no longer appropriate, pts are eligible for either reg or t/t treatment. Although both treatments are approved in mCRC, no randomised trial has investigated the sequence of reg and t/t. The optimal strategy to extend survival while maintaining quality of life still needs to be determined. We have designed this trial to evaluate both treatment sequences and determine the best one in this setting. This international, randomized phase II, open-label trial is designed to compare the feasibility of the treatment sequences: reg followed by t/t vs t/t followed by reg. Pts ≥18 years, with mCRC, ECOG PS 0-1, after failure of fluoropyrimidine-based chemotherapy combined with oxaliplatin and/or irinotecan as well as EGFR (if RAS wild-type) and/or VEGF inhibitors are enrolled. Reg will be given according to ReDOS dose-escalation scheme at 1st cycle (increasing from 80 mg to 160 mg daily over 3 weeks) to determine the highest dose tolerated that will be then used for the next cycles (3 weeks followed by 1 week off). T/t 35 mg/m2 will be taken orally twice daily on D1-D5 and D8-D12 of each 4-week cycle. The primary endpoint is the treatment feasibility of the 2 sequences, assessed as the percentage of pts able to receive at least 2 cycles of both treatments, which corresponds to the first tumor evaluation at each line. If a pt does not receive the second treatment, he will be considered a failure. Secondary endpoints are overall survival, progression-free survival, disease control rate, objective response rate, time to treatment failure, time to ECOG PS ≥2 deterioration, quality of life and safety. We assume that 50% of the pts receiving t/t will be able to receive further treatment as compared to 65% with reg. With a Chi-square test between the 2 arms, a bilateral α-risk of 5% and a power of 80%, 170 pts are required in each arm. Since November 2020, 42 pts are enrolled in 14 sites. NCT04450836 - initial release 24 June 2020 EudraCT 2019-004196-39. UNICANCER, a private, non-profit French healthcare cooperative group, with its registered offices at 101, rue de Tolbiac, 75654 Paris, France. Bayer HealthCare Pharmaceuticals Inc.

After failure to FOLFIRINOX or gemcitabine + nab-paclitaxel combination, no clinical trial evaluated prospectively the benefit of a second line chemotherapy. Phases III clinical studies currently available enrolled only patients who progressed under gemcitabine treatment. It does not exist any strong argument in favor of or against actual place of second line chemotherapy after failure to first line FOLFIRINOX or gemcitabine + nab-paclitaxel therapy. Potential usefulness of taxanes was demonstrated with nab-paclitaxel. However, the potential efficacy of docetaxel or paclitaxel in metastatic pancreas cancer was evaluated only in small non-randomized studies and mainly after failure to first line gemcitabine. Thus, taking into account the absence of second line prospective studies, a similar mechanism of action between nab-paclitaxel and paclitaxel, and a reduced cost of paclitaxel, our study aims to evaluate the combination of gemcitabine + paclitaxel in the treatment of metastatic pancreas cancer after failure or intolerance to FOLFIRINOX. Comparative, multicentric, phase III randomized, open-label trial enrolling patients ≥18 years, with metastatic pancreatic ductal adenocarcinoma, ECOG performance status 0-2, after failure or intolerance of first line FOLFIRINOX therapy. The primary objective of the study is to evaluate the superiority of the combination of gemcitabine + paclitaxel over gemcitabine monotherapy in terms of overall survival (OS) (8 months vs 5 months with HR=0,625). Main secondary criteria are progression-free survival, disease control rate at 4 months, objective response rate, safety, and quality of life. Paclitaxel 80 mg/m2 and gemcitabine 1000 mg/m2 will be given at day 1, day 8, and day 15, followed by one week of rest, every 28 days. 184 events (deaths) would have 85% power to show statistically significant OS at a 2-sided 5% alpha. 210 patients will be randomized (70 patients in the control arm and 140 patients in the experimental arm). We programmed an interim analysis of efficacy to be performed after half of the planned events will have occurred. NCT03943667. UNICANCER. Institut National du Cancer (INCa).

BACKGROUND:The effect of treatment delay on survival in pancreatic ductal adenocarcinoma (PDAC) remains unclear. AIMS:This study aimed to assess the prognostic impact of time to diagnosis and chemotherapy in advanced PDAC and factors influencing the time intervals. METHODS:advanced PDAC patients receiving chemotherapy in five centers in the decade 2007-2016 were included. Key time points during care pathway from clinical presentation to beginning of chemotherapy were retrospectively collected. Multivariate Cox proportional hazard model was performed. RESULTS:A total of 409 patients were included (mean age 66.1 ± 10.3 years; 250 metastatic (61%); 139 received FOLFIRINOX chemotherapy (34%). The median overall survival (OS) was 7.2 months. The median times from first symptoms and from first specialist visit to the beginning of chemotherapy were respectively 100 days and 47 days. None of time intervals was significantly associated with OS. Significant prognostic factors were FOLFIRINOX chemotherapy (HR 0.6 [0.5-0.8]; P < 0.001), metastasis (HR 1.6 [1.3-2.0]; P = 0.001), WHO PS ≥ 2 (HR 1.6 [1.2-2.1]; P < 0.001) and acute pancreatitis as first symptom (HR 2.9 [1.7-4.9]; P < 0.001). Jaundice shortened time to diagnosis (P < 0.001). Acute pancreatitis (P < 0.001) and diabetes (P = 0.01) increased time to treatment. CONCLUSION:Wait times from clinical presentation to beginning of chemotherapy do not influence survival in advanced PDAC.

Les chambres implantables sont des dispositifs médicaux utilisés en oncologie pour l’administration par voie veineuse centrale de produits cytotoxiques, d’antibiotiques ou de nutrition parentérale. Les complications les plus fréquemment rapportées sont d’ordre infectieux, thrombotique ou mécanique. Le mauvais positionnement du cathéter est une complication rare. Seule une dizaine d’observations de diffusion médiastinale a été décrite. Les cas de deux patients présentant un cathéter en position médiastinale sont rapportés. La vérification du bon positionnement du cathéter pendant l’intervention sous contrôle radioscopique avec amplificateur de brillance puis par une radiographie thoracique ainsi que l’existence d’un retour veineux sont des éléments indispensables à prendre en compte avant l’utilisation d’une chambre implantable. La douleur précoce à la perfusion doit être un signe d’alerte.