Low skeletal muscle mass and impaired muscle quality (myosteatosis) have been associated with poor outcomes in cancer patients. This study aimed to evaluate the impact of pre-therapeutic low muscle mass and myosteatosis on chemoradiotherapy (CRT)-induced toxicity and survival outcomes in patients with non-resectable pancreatic cancer (PC). In this retrospective study, pre-therapeutic CT scans were used to measure muscle mass/density. Low muscle mass was defined as a skeletal muscle index <38.5 cm²/m² (women) and <52.4 cm²/m² (men), and myosteatosis as a mean psoas density <41 HU if BMI < 25 kg/m² or <33 HU if BMI > 25 kg/m². Adverse effects were collected per week (W) of treatment. Dose-limiting toxicity (DLT) was defined as any toxicity leading to dose reduction, treatment delays or permanent discontinuation. Among the 85 included patients, 75 (88.2

INTRODUCTION:Predictive markers of LV5FU2 maintenance benefit after first-line induction with FOLFIRINOX in patients with metastatic pancreatic cancer are necessary to select patients who will not be harmed by this strategy. PATIENTS AND METHODS:We focused on patients who received 12 cycles of FOLFIRINOX (arm A, N = 88) or 8 cycles of FOLFIRINOX followed by LV5FU2 maintenance in controlled patients (arm B, N = 91) from the PRODIGE-35 trial. Prognostic factors and predictors of efficiency were identified by using Cox regression. Median progression-free survival (PFS), overall survival (OS), and time to deterioration of quality of life (TTD-QoL) were evaluated. RESULTS:Poor independent prognostic factors were primary tumor in place, age <65 years and the presence of liver metastases for PFS, a baseline neutrophil/lymphocyte ratio (NLR) ≥5 and CA19.9 ≥500 UI/L for OS, independent of the treatment arm. Patients with one metastatic site had a longer PFS in arm A, whereas patients with ≥2 metastatic sites had a longer PFS in arm B. We also identified predictors of OS and TTD-QoL in arm B but these differences were not statistically significant. CONCLUSION:Except for patients with one metastatic site who benefited more from 12 cycles of FOLFIRINOX, a maintenance strategy with LV5FU2 should be widely offered to mPC patients whose survival and QoL are preserved after 4 months of FOLFIRINOX. (ClinicalTrials.gov: NCT02352337).

Background: The results of the PRODIGE 42/GERICO 12 study showed that short course radiotherapy had a better tolerance profile than radiochemotherapy, with comparable oncological results. We have included Quality of Life analyses and oncogeriatric evaluations in this study. Patients and methods: In all, 101 patients >= 75 years of age with resectable T3-T4 rectal adenocarcinoma less than 12 cm from the anal margin received short course radiotherapy (5X5 Gy in one week) or radiochemotherapy (50 Gy, 2 y/f and capecitabine 800 mg/m2, 5 days/week) with delayed surgery (7 weeks +/- 1) in both groups. The Quality of Life analyses (EORTC QLQ C-30 et ELD14) were conducted upon inclusion, pre-operatively, at 3, 6 and 12 months post-op, together with the oncogeriatric evaluations, including an evaluation of the IADL and ADL scores, walking speed, GDS15, MMSE, MNA. Results: We did not highlight any statistical difference for the global EORTC QLQ-C30 score; several factors are statistically in favor of the short course radiotherapy group at 3 months post-op (cognitive functions, fatigue, appetite). In the case of the ELD14 score, the disease burden is perceived as more negative at 3, 6 and 12 months postop in the radiochemotherapy group. The IADL score deteriorated in 44.8 % of the radiochemotherapy group and 14.8 % of the radiotherapy group (p = 0.032); similarly, the GDS15 depression score was better preserved in the short course radiotherapy group (p = 0.05). An analysis of the other scores: ADL, walking speed, MNA, MMSE did not highlight any statistical difference. Conclusion: Short course radiotherapy achieves better results in terms of Quality of Life and preservation of autonomy in patients aged >= 75 treated for locally advanced rectal cancer.

Figure S1 shows a comparison of quantitative HPV ctDNA at baseline with ddPCR assay and QPCR assay (Spearman r=0.803, 95% CI 0.672 to 0.885, P<0.001).

ImportanceThe optimal maintenance strategy after induction chemotherapy with anti–epidermal growth factor receptor antibody for patients with RAS wild-type metastatic colorectal cancer (mCRC) remains to be debated.ObjectiveTo evaluate the efficacy and safety of maintenance therapy with single-agent cetuximab after FOLFIRI (leucovorin [folinic acid], fluorouracil, and irinotecan) plus cetuximab induction therapy.Design, Setting, and ParticipantsThe TIME (Treatment After Irinotecan-Based Frontline Therapy: Maintenance With Erbitux]) (PRODIGE 28 [Partenariat de Recherche en Oncologie Digestive]–UCGI 27 [UniCancer GastroIntestinal Group]) phase 2 noncomparative, multicenter randomized clinical trial was conducted from January 15, 2014, to November 23, 2018, among 139 patients with unresectable RAS wild-type mCRC. The cutoff date for analysis was July 21, 2022.InterventionsAfter first-line induction therapy with 8 cycles of FOLFIRI plus cetuximab, patients without disease progression were randomized (1:1) to biweekly maintenance with cetuximab or observation. On disease progression, the same induction regimen was recommended for 16 weeks followed by further maintenance with cetuximab or observation until disease progression under the full induction regimen.Main Outcomes and MeasuresThe primary end point was the 6-month progression-free rate from randomization. Analysis was performed on an intention-to-treat basis. An exploratory biomolecular analysis, using next-generation sequencing, investigated the putative prognostic value of the tumor mutation profile.ResultsOf 214 patients enrolled (141 men [65.9%]; median age, 67 years [range, 23-85 years]), 139 were randomized to receive cetuximab (n = 67; 45 men [67.2%]; median age, 64 years [range, 34-85 years]) or to be observed (n = 72; 50 men [69.4%]; median age, 68 years [23-85 years]). The 6-month progression-free rate was 38.8% ([26 of 67] 95% CI, 27.1%-51.5%) in the cetuximab group and 5.6% ([4 of 72] 95% CI, 1.5%-13.6%) in the observation group. At a median follow-up of 40.5 months (95% CI, 33.6-47.5 months), median progression-free survival (PFS) from randomization was 5.3 months (95% CI, 3.7-7.4 months) in the cetuximab group and 2.0 months (95% CI, 1.8-2.7 months) in the observation group. Median overall survival (OS) was 24.8 months (95% CI, 18.7-30.4 months) in the cetuximab group and 19.7 months (95% CI, 13.3-24.4 months) in the observation group. In an exploratory multivariate analysis, any tumor-activating mutation in the mitogen-activated protein kinase (MAPK) pathway genes was associated with shorter PFS from randomization regardless of treatment group (hazard ratio, 1.63 [95% CI, 1.01-2.62]; P = .04). The most frequent grade 3 or 4 treatment-related toxic effect in the cetuximab group during maintenance therapy was rash (8 of 67 [11.9%]).Conclusion and RelevanceThe randomized clinical trial did not meet its primary end point but suggests clinically meaningful PFS and OS benefits associated with cetuximab maintenance therapy. However, maintenance cetuximab or treatment breaks after first-line combination FOLFIRI-cetuximab therapy seems inappropriate for patients with MAPK-mutated independently of the side of primary tumor. A more complete assessment of MAPK pathway mutations warrants further investigation to the refine treatment strategy for patients with RAS wild-type mCRC.Trial RegistrationClinicalTrials.gov Identifier: NCT02404935

<p>Supplementary materials and figures</p>

Background: There is no specific guideline for the treatment of locally advanced rectal cancers in the elderly. Here we compared R0 resection rate and degradation of auton-omy based on the instrumental activities of daily living score between neoadjuvant, short course radiotherapy and chemoradiotherapy in this specific population.Patients and methods: Patients >75 years with resectable T3-T4 rectal adenocarcinoma within 12 cm of the anal verge or T2 of the very low rectum were randomised between short course radiotherapy (5 x 5 Gy in one week) and chemoradiotherapy (50 Gy, 2 Gy/f, 5 weeks with capecitabine: 800 mg/m2 twice daily, 5 days per week), with delayed surgery 7 +/- 1 weeks for the two arms.Results: One hundred and three eligible patients were enrolled between January 2016 and December 2019 when the trial was closed due to poor accrual. The R0 resection rate (first co-primary objective) was 84.3%; confidence interval 95% [73.26-94.18] in the short course group and 88%; confidence interval 95% [77.77-96.60] in the chemoradiotherapy group (non-inferiority p = 0.28). The deterioration of the instrumental activities of daily living score was not different during the pre-operative phase, it was significantly more deteriorated in the chemoradiotherapy group at 3 months post-operative (44.8% versus 14.8%; p = 0.032) but was not different at 12 months post-operative (second co-primary objective). During pre-operative phase, 9.8% of patients in short course group and 22% of patients in chemora-diotherapy group presented a serious adverse event, but we observed no difference during the post-operative phase between the two groups.Conclusion: Although the main objectives of the study were not achieved, the short course radiotherapy followed by delayed surgery could represent a preferred treatment option in pa-tients >75 years with locally advanced rectal cancer; a new study must be performed to confirm the improvement in overall and specific survival results. 2022 Elsevier Ltd. All rights reserved.

12102 Background: In 2010, Temel et al. reported that early palliative care (PC) (EPC) led to significant improvements in quality of life and, surprisingly, on overall survival (OS) over standard oncologic care (SOC) for patients (pts) with metastatic lung cancer. The American Society of Clinical Oncology then recommended “combined standard oncology care and PC earlier in the course of the illness for any patient with metastatic cancer”. The median OS of unselected pts with metastatic upper gastrointestinal cancers (mUGIC) does not exceed 11 m. Whether EPC benefits also apply to pts with mUGIC was unknown. Methods: EPIC (NCT02853474) is a randomized 1:1, open-label, multicenter, phase 3 trial aiming to evaluate the OS benefit of EPC compared to SOC in pts with mUGIC (esophageal, HER2 negative esogastric junctional and gastric, pancreatic, and biliary tract cancers), with ECOG PS ≤ 2, to be treated by first-line chemotherapy (CT). EPC included 5 PC visits scheduled every month, starting within 3 weeks of randomization. Pts allocated to SOC could access to PC visits upon request in case of worsening of health status. The primary endpoint was OS. Other endpoints included quality of life, and depression and anxiety assessment. A total of 381 deaths was required (1 year OS 40% vs. 50.3%, HR = 0.75, 2-sided alpha 5%, 80% power). Randomization was balanced on center, ECOG-PS and tumor site. Results: 473 pts were randomized from 10/2016 to 12/2021 in 19 French centers. Modified intention-to-treat population was 470. Median age = 67.5 (range, 24-90); 273 males; tumor site: esophagus 39, esogastric 48, pancreas 297, biliary tract 86; ECOG PS 0/1/2: 104/278/88. 74/233 pts (32%) in EPC arm had less than the planned EPC visits (major deviation): 3 related to treatment, 17 due to pt decision, 45 due to the clinical team decision, 2 other reasons, 7 unknown. 57/237 pts in the SOC arm got at least 1 PC visit, including 3 major deviation (performed < 6 months of treatment and set for a reason other than worsening of the health condition). Median follow-up was 46 m, and 35/470 pts were still alive. We did not observe any OS difference between arms (EPC, median OS: 7.0 m [95%CI: 6.1-8.8 m] and 1-year OS: 33%; SOC, median OS: 8.6 m [6.8-9.8 m] and 1-year OS: 32%; stratified HR = 1.04 [0.86-1.26], p = 0.68). Results were similar on the per-protocol dataset (excluding major violations). Results were homogeneous across the different tumor locations, and ECOG-PS groups. Conclusions: OS was lower than expected in both arms, which may reflect the difference between pharma-sponsored and academic trials with less stringent exclusion criteria. Also, only 68% of the pts got the planned number of PC visits in the experimental arm. EPC was not found to prolong OS over SOC in pts with mUGIC in this EPIC trial. Clinical trial information: NCT02853474 .

Triplet DCF (docetaxel, cisplatin and 5-flurouracil) and doublet CP/CF (carboplatin and paclitaxel/cisplatin and 5-fluorouracil) regimens were prospectively evaluated in advanced squamous anal cell carcinoma (SCCA), and validated as standard treatments. Even though the high efficacy and good tolerance of DCF regimen were confirmed in 3 independent prospective trials, doublet CP regimen is still recommended in several guidelines based in its better safety profile with similar efficacy compared to CF regimen. We performed a propensity score-adjusted method with inverse probability of treatment weighted (IPTW) and matched case control (MCC) comparison among patients with metastatic or non-resectable locally advanced recurrent SCCA, treated with chemotherapy as first line regimen. The primary endpoint was the overall survival (OS), and the secondary endpoint was the progression-free survival (PFS). 247 patients were included for analysis. 154 patients received DCF and 93 patients received a doublet regimen. The median OS was 32.3 months with DCF and 18.3 months with doublet regimens (HR 0.53, 95%CI 0.38–0.74; p = 0.0001), and the median PFS was 11.2 months with DCF versus 7.6 months with doublet regimens (HR 0.53, 95%CI 0.39–0.73; p < 0.0001). The hazard ratios by IPTW and MCC analyses were 0.411 (95% CI, 0.324–0.521; p < 0.0001) and 0.406 (95% CI, 0.261–0.632; p < 0.0001) for OS, and 0.466 (95% CI, 0.376–0.576; p < 0.0001) and 0.438 (95% CI, 0.298–0.644; P < 0.0001) for PFS. The triplet DCF regimen provides a high and significant benefit in OS and PFS over doublet regimens, and should be considered as upfront treatment for eligible patients with advanced SCCA.

PURPOSE:GemPred, a transcriptomic signature predictive of the efficacy of adjuvant gemcitabine (GEM), was developed from cell lines and organoids and validated retrospectively. The phase III PRODIGE-24/CCTG PA6 trial has demonstrated the superiority of modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) over GEM as adjuvant therapy in patients with resected pancreatic ductal adenocarcinoma at the expense of higher toxicity. We evaluated the potential predictive value of GemPred in this population. PATIENTS AND METHODS:Routine formalin-fixed paraffin-embedded surgical specimens of 350 patients were retrieved for RNA sequencing and GemPred prediction (167 in the GEM arm and 183 in the mFOLFIRINOX [mFFX] arm). Survival analyses were stratified by resection margins, lymph node status, and cancer antigen 19-9 level. RESULTS:Eighty-nine patients' tumors (25.5%) were GemPred+ and were thus predicted to be gemcitabine-sensitive. In the GEM arm, GemPred+ patients (n = 50, 30%) had a significantly longer disease-free survival (DFS) than GemPred- patients (n = 117, 70%; median 27.3 v 10.2 months, hazard ratio [HR], 0.43 [95% CI, 0.29 to 0.65]; P < .001) and cancer-specific survival (CSS; median 68.4 v 28.6 months, HR, 0.42 [95% CI, 0.27 to 0.66]; P < .001). GemPred had no prognostic value in the mFFX arm. DFS and CSS were similar in GemPred+ patients who received adjuvant GEM and mFFX (median 27.3 v 24.0 months, and 68.4 v 51.4 months, respectively). The statistical interaction between GEM and GemPred+ status was significant for DFS (P = .008) and CSS (P = .004). GemPred+ patients had significantly more adverse events of grade ≥3 in the mFFX arm (76%) compared with those in the GEM arm (40%; P = .001). CONCLUSION:This ancillary study of a phase III randomized trial demonstrates that among the quarter of patients with a GemPred-positive transcriptomic signature, survival was comparable with that of mFOLFIRINOX, whereas those receiving adjuvant gemcitabine had fewer adverse events.

<p>Figure S2 shows the ROC curve analysis of progression prediction according to the HPV ctDNA level at baseline. (AUC was 0.646 (95% CI 0.49 to 0.802) and 2940 copies/ml was determined as the ctDNA cut-off level for comparison. Sensitivity and specificity of the cut-off were 67% and 70% respectively).</p>

Currently, there are no reliable biomarkers to predict the effectiveness of FOLFIRINOX/FOLFOX regimens. Predictive tests that assist clinicians in choosing the most appropriate first-line chemotherapy regimen are needed. In 2022, we developed a blood-based RNA signature, the GemciTest, which predicts the response to gemcitabine-based first-line treatment in patients with PDAC. The objective of this study was to evaluate the effectiveness of a complementary blood-based RNA signature (F/FX) to predict the response to FOLFIRINOX/FOLFOX regimens in advanced pancreatic adenocarcinoma. Clinical validation was conducted through a discovery and a validation phase on 164 previously untreated advanced PDAC patients (at baseline) (mean age of 68.7 years; 37-88) who received either a gemcitabine- or fluoropyrimidine-based regimen (Id.: NCT03599154 and NCT02818829). The F/FX test measures the expression levels of ten genes using real-time PCR process (MCEMP1, S100A12, MMP9, RACK1, DSC2, LYN, LPP, ARL4C, ALDOA and AC007877.1). Among FOLFIRINOX/FOLFOX treated patients (n=90), those with a positive F/FX (31.1%) had a significantly longer progression-free survival (PFS) (14.3 vs. 3.5 months; HR=0.21 (95% confidence interval CI: 0.12–0.35); p=5.56e-09) and median overall survival (OS) (23 vs. 7.7 months; HR=0.22 (95% CI: 0.13–0.36); p=3.16e-09). The Pearson correlation coefficient between OS and PFS was 0.73 (95% CI: 0.62-0.81; p=2,2E-16). On the contrary, gem-based treated patients (n=74) showed no significant difference in PFS (11.3 vs. 5.8 months; HR=0.68 (95% CI: 0.24–1.91); p=0.48) and OS (13.6 vs. 7.3 months; HR=0.7 (95% CI: 0.25–1.95); p=0.5) between the patients with a positive F/FX versus the patients with a negative F/FX. The F/FX demonstrates the potential of a blood-based RNA signature as a minimally-invasive alternative to improve patient survival and implement personalized therapy in PDAC for patients treated with a FOLFIRINOX/FOLFOX regimen as first-line treatment. While these data show promise, they should be confirmed in a prospective trial, distinguishing patients with non resectable locally advanced and those with metastatic tumors.

BACKGROUND AND PURPOSE:The aim of our prospective study was to assess the prognostic value of 18F-FDG PET/CT performed two months post treatment for anal canal neoplasm. POPULATION AND METHODS:Consecutive patients with histologically proved anal cancer, with 18F-FDG PET/CT pre and two months post treatment were included. Patients were not previously treated for this neoplasm and then received radiotherapy ± chemotherapy. Clinical and pathologic data were collected and for 18F-FDG PET/CT visual and quantitative analysis (standardized uptake value, metabolic volume) were performed; response was classified according to EORTC and PERCIST criteria. The results were assessed for disease free survival and local recurrence free survival using the log-Rank test RESULTS: From December 2014 to September 2019, 94 consecutive patients were screened and 78 were included in this study. Median follow-up was 51 months. Two months post treatment, 37 patients (47.4%) had a complete radiological response according to both EORTC and PERCIST criteria, 66 patients (84.6%) had a clinical complete response. For disease free survival, the prognostic value of complete response was statistically significant (p=0.02) with 18F-FDG PET/CT and with clinical examination (p<0.001). For local recurrence free survival, the prognostic value with 18F-FDG PET/CT was lower (p=0.04) than clinical examination (p < 0.007). CONCLUSION:While clinical examination remains the gold standard for post treatment evaluation in anal cancer, 18F-FDG PET/CT has a statistically significant prognostic value. These two assessments could be combined to improve early evaluation.

Background and objective: Longitudinal analysis of patient-reported outcome (PRO) data remains challenging, as no standardization of statistical methods has been proposed, making comparison of PRO results between clinical trials difficult. In this context, the time to deterioration approach has recently been proposed and is regularly used as a modality of longitudinal PRO analysis in oncology. Methods: Two new SAS macro programs were developed, %TTD and %TUDD, which implement longitudinal analysis of PRO data according to the time to deterioration approach. These programs implement the recommended deterioration definitions. We described the programs with their different functionalities. Results: The %TTD macro calculates the time to first or transient deterioration, and the %TUDD macro calculates the time until definitive deterioration. These macros allow to obtain the survival variables from the time to deterioration approach. We illustrate our programs by presenting different applications on the randomized phase II AFUGEM GERCOR clinical trial. Conclusion: The implementation of the deterioration definitions in SAS software allows the dissemination of this approach, in order to move toward the goal of standardization of longitudinal PRO analysis in oncology clinical trials. (C) 2021 Elsevier B.V. All rights reserved.

Background Colorectal cancer (CRC) patients have a better prognosis if metastases are resectable. Initially, unresectable liver-only metastases can be converted to resectable with chemotherapy plus a targeted therapy. We assessed which of chemotherapy doublet (2-CTx) or triplet (3-CTx), combined with targeted therapy by RAS status, would be better in this setting. Methods PRODIGE 14 was an open-label, multicenter, randomised Phase 2 trial. CRC patients with initially defined unresectable liver-only metastases received either, 2-CTx (FOLFOX or FOLFIRI) or 3-CTx (FOLFIRINOX), plus bevacizumab/cetuximab by RAS status. The primary endpoint was to increase the R0/R1 liver-resection rate from 50 to 70% with the 3-CTx. Results Patients ( n = 256) were mainly men with an ECOG PS of 0, and a median age of 60 years. In total, 109 patients (42.6%) had RAS-mutated tumours. After a median follow-up of 45.6 months, the R0/R1 liver-resection rate was 56.9% (95% CI: 48–66) with the 3-CTx versus 48.4% (95% CI: 39–57) with the 2-CTx ( P = 0.17). Median overall survival was 43.4 months with 3-CTx versus 40 months with 2-CTx. Conclusion We failed to increase from 50 to 70% the R0/R1 liver-resection rate with the use of 3-CTx combined with bevacizumab or cetuximab by RAS status in CRC patients with initially unresectable liver metastases.

Background: Several studies have reported the impact of single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor ( VEGF ) pathway genes on the efficacy of bevacizumab in metastatic colorectal cancer (mCRC), but results are still inconsistent. The PRODIGE 9 phase III study compared bevacizumab maintenance versus observation alone after induction chemotherapy with FOLFIRI plus bevacizumab. Objective: We evaluated the impact of SNPs of VEGF-A , VEGF receptors ( VEGFR-1, VEGFR-2 ), and hypoxia inducible factor-1α ( HIF-1α ) on tumor control duration (TCD), overall survival (OS), progression-free survival (PFS), and duration of first chemotherapy free-intervals (CFI). Patients and methods: We included 314/491 patients from PRODIGE 9 with a DNA blood sample available. Nine SNPs were genotyped on germline DNA using real-time Polymerase Chain Reaction TaqMan TM (Thermo Fisher Scientific, Waltham, MA , USA 02451). Results: In the bevacizumab arm, patients with the VEGFR-1 rs9582036 CC genotype ( n = 14) had significantly longer TCD [22.4 months (95% confidence interval (CI): 14.75-not reached)] than patients with the AA or CA genotype [14.4 months (95% CI: 11.7–17.1)] ( p = 0.036), whereas there was no significant difference in the observation arm. In the bevacizumab arm, no significant difference was found between the CC, and AA or CA genotype for OS [28.2 (95% CI: 18.1–42.8) versus 22.5 (95% CI: 18.6–24.6) months, p = 0.5], PFS [9.4 (95% CI: 7.2–11.3) versus 9.2 (95% CI: 8.71–10.1)], and duration of the first CFI [4.6 (95% CI: 1.6–13.3) versus 4.14 (95% CI: 0.5–29.0) months, p = 0.3]. Conclusion: Among mCRC patients treated with bevacizumab maintenance, those with the VEGFR-1 rs9582036 CC genotype experienced longer TCD. The presence of this genotype may thus predict a benefit of bevacizumab maintenance in mCRC.

In squamous cell anal canal neoplasms, persistent disease or recurrence after initial chemoradiotherapy are not the rule, yet their occurrence deserves to be analyzed to better identify prognostics factors. The aim of our study was to describe the patterns of failures of the initial treatment, their subsequent evolution and to identify prognostic factors in these relapsed patients. All patients with non-metastatic anal squamous cell carcinoma initially treated with curative intent at the Centre Antoine Lacassagne between 1999 and 2019, and who presented persistent disease or recurrence were analyzed. The median follow-up was 44 months. Univariate and multivariate analyses were performed to identify prognostic factors. From our database of 528 patients, 77 patients were eligible: 25 with persistent disease and 52 with recurrence after complete response. The median overall survival was 39 months (95% CI: 25.5-52.3 months) from the date of treatment failure. In univariate analysis, prognostic factors were gender, initial lymph node status, type of failure, response to treatment's failure. In multivariate analysis, only female gender remained statistically significant (HR 0.43- P=0.016). 32% of patients with persistent disease had metastatic status. 17.3% and 5.8% of recurrences respectively occurred after three and five years of follow-up. Systematic imaging could be performed after initial treatment because of distant lesions in one third of patients with persistent disease. The follow-up should not be interrupted before five years, given the significant frequency of late recurrences. In multivariate analysis, only female gender was statistically significant. Stratified treatment based on prognostic factors could be envisaged, the details of which remain to be defined.

Introduction Patients ≥ 70 years old constitute 40% of patients with advanced gastric cancer (GC). Ramucirumab plus Paclitaxel is a therapeutic option validated in the second-line treatment of advanced GC, but as older patients are at higher risk of severe toxicity, due to comorbidities and/or frailty, we aimed to evaluate second-line Ramucirumab alone or combined with Paclitaxel in terms of overall survival (OS) and quality of life (QoL) in patients ≥ 70 years-old with advanced GC. Methods In this multicenter, randomized, open-label, non-comparative, prospective phase II clinical trial, the main inclusion criteria are: patients ≥ 70 years old, with advanced GC having progressed after first-line chemotherapy or in the six months following the last administration of adjuvant chemotherapy, with WHO performance status <2. They are randomized to receive either ramucirumab alone (arm A) or ramucirumab plus Paclitaxel (arm B). The primary endpoint is 6-month OS and QoL evaluated with the EORTC QLQ-ELD14 questionnaire. The secondary endpoints include other parameters of QoL, time to definitive deterioration (TTDD) in QoL and TTDD in autonomy, treatment toxicities, other parameters of survival and disease control, identification of geriatric and nutritional prognostic scores and predictive factors of treatment safety and efficacy. OS of 60% is expected at 6 months (H0:40%). Using a Simon-minimax design, with one-sided α risk of 2% and 80% power for OS, and considering 5% lost to follow-up, it is necessary to randomize 56 patients in each arm. Perspectives As older patients are at higher risk of chemotherapy toxicity, ramucirumab alone could be an interesting alternative to Paclitaxel plus ramucirumab, as a second-line therapy for patients ≥ 70 years old with advanced GC, and needs to be evaluated.