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Purpose: The objective of this work was to establish prognostic models in stage III colon cancer (CC) on the basis of transcriptomic signatures of the tumor microenvironment (TME) and cell cycle from the PETACC-8 (training set) and IDEA-France (validation set) trials., Patients and Methods: 3'RNA sequencing was performed in 1,733 patients from the PETACC-8 trial and 1,248 patients from the IDEA-France trial. Four transcriptomic signatures were analyzed: T-cell and macrophage M2 signatures, the expression of CXCL13, and a score on the basis of the Oncotype DX CC Recurrence Score using the same formula from the stromal score and the cell cycle score. The Immune Proliferative Stromal (IPS) score was defined as the number of dichotomized signatures that fall under the category of a dismal prognosis (from 0 to 4). Time to recurrence (TTR) was defined as the time from the date of random assignment to local and/or metastatic relapse and/or death because of CC, whichever occurs first., Results: High Oncotype-like and M2 scores and low CXCL13 expression and T-cell score were associated with a shorter TTR. A multivariable model including these signatures and all known prognostic factors applied to the IDEA-France cohort by obtaining a value of this model for each patient showed TTR significantly different depending on the quartile of this value and a 3-year rate of patients without recurrence ranging from 56% for the lowest quartile to 89% for the highest quartile ( P < .0001). The IPS score was significantly associated with TTR in multivariable analysis., Conclusion: Using transcriptomic data of patients with stage III CC from two large-scale adjuvant trials, a prognostic model on the basis of signatures of the TME and the cell cycle provides important information in addition to known prognostic factors for patient stratification on risk of recurrence.

Purpose: Metastatic pancreatic cancer (mPC) still harbors a dismal prognosis. Our previous trial (PRODIGE 4-ACCORD 11) demonstrated the superiority of 6-month chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) over gemcitabine for overall survival. The high limiting oxaliplatin-related neurotoxicity supports the evaluation of an oxaliplatin stop-and-go strategy and a sequential strategy in mPC., Methods: In this phase II study, patients were randomly assigned to receive either 6 months of FOLFIRINOX (arm A), 4 months of FOLFIRINOX followed by leucovorin plus fluorouracil maintenance treatment for controlled patients (arm B), or a sequential treatment alternating gemcitabine and fluorouracil, leucovorin, and irinotecan every 2 months (arm C). The primary end point was progression-free survival at 6 months., Results: Between January 2015 and November 2016, 276 patients (mean age: 63 years; range: 40-76 years) were enrolled (A: 91, B: 92, and C: 90). Grade 3 or 4 neurotoxicity occurred in 10.2% of patients in arm A and 19.8% in arm B. The median ratio of received dose/targeted dose of oxaliplatin was 83% in arm A and 92% in arm B. The 6-month progression-free survival was 47.1% in A, 42.9% in B, and 34.1% in C. The median overall survival was 10.1 months in arm A, 11.2 in arm B, and 7.3 in arm C. Median survival without deterioration in quality-of-life scores was higher in the maintenance arm (11.4 months) than in arms A and C (7.2 and 7.5 months, respectively)., Conclusion: Maintenance with leucovorin plus fluorouracil appears to be feasible and effective in patients with mPC controlled after 4 months of induction chemotherapy with FOLFIRINOX. Severe neurotoxicity was higher in the maintenance therapy arm, probably because of the higher cumulative dose of oxaliplatin., Competing Interests: Laetitia DahanHonoraria: Amgen, BMS, Servier, Oseus, Mylan Jean-Marc PhelipHonoraria: Merck Serono, Roche, Sanofi, Amgen, Lilly, Servier, BayerConsulting or Advisory Role: Roche, Merck Serono, Amgen, Servier, Bayer, SanofiResearch Funding: Roche, Merck SeronoTravel, Accommodations, Expenses: Roche, Merck Serono, Bayer, Servier, Sanofi, Amgen Jérôme DesrameExpert Testimony: RocheTravel, Accommodations, Expenses: Hospira Olivier BouchéConsulting or Advisory Role: Roche, Merck Serono, Bayer, MSD Oncology, Grünenthal Group, AstraZenecaSpeakers' Bureau: Pierre Fabre, Servier, Amgen, SanofiTravel, Accommodations, Expenses: Roche, Merck Serono, Servier David MalkaHonoraria: Roche, Amgen, Bayer, Merck Serono, Servier, Sanofi, HalioDx, Pierre Fabre, Viatris, Bristol Myers Squibb, MSD Oncology, LEO PharmaConsulting or Advisory Role: Roche, Sanofi, Merck Serono, MSD, Servier, Bayer, Incyte, Amgen, HalioDx, Agios, Bristol Myers SquibTravel, Accommodations, Expenses: Roche, Bayer, Sanofi, Merck Serono, Amgen, Servier Thomas AparicioHonoraria: Roche, Amgen, Servier, AstraZenecaConsulting or Advisory Role: MSD Oncology, Bioven, ServierTravel, Accommodations, Expenses: Roche Yves RinaldiHonoraria: Viatris, Amgen Astellas BioPharma Anthony TurpinHonoraria: Amgen, Merck Serono, ServierConsulting or Advisory Role: AmgenTravel, Accommodations, Expenses: AstraZeneca, Pfizer, Sanofi, Merck Anne-Laure BignonHonoraria: IpsenTravel, Accommodations, Expenses: Ipsen Jean-Baptiste BachetHonoraria: Amgen, Bayer, Merck Serono, Sanofi, Roche, Servier, AstraZeneca, Pierre FabreConsulting or Advisory Role: Amgen, Bayer, Merck Serono, Servier, AstraZeneca, Pierre FabreTravel, Accommodations, Expenses: Merck Serono, Amgen, Roche, Servier Jean-François SeitzHonoraria: Lilly, Merck Serono, SanofiConsulting or Advisory Role: Servier, Pierre FabreTravel, Accommodations, Expenses: Ipsen Come LepageHonoraria: Amgen, Bayer, Ipsen, Pierre FabreConsulting or Advisory Role: Advanced Accelerator Applications, NovartisTravel, Accommodations, Expenses: Novartis, Bayer, Sanofi/Aventis, Merck Serono, Ipsen Eric FrançoisHonoraria: Amgen, Servier, Novartis, Merck Sharp & DohmeConsulting or Advisory Role: Roche, Pierre FabreTravel, Accommodations, Expenses: Roche, ServierNo other potential conflicts of interest were reported.