The work of our team at ASCO 2024

Founded in 1964, the American Society of Clinical Oncology (ASCO) is the world's leading professional organization for physicians, researchers and specialists in the field of oncology.

Major annual event for clinical research and innovation in oncology, the ASCO International Conference is held every year in Chicago. Several tens of thousands of international specialists meet there to present research that aimed at improving treatment standards and patient care. https://conferences.asco.org/

For the 2024 edition, our team was involved in the following studies:

REPROGRAM-02: A phase II-III study evaluating an induction treatment with regorafenib and metronomic chemotherapy before the second line chemotherapy in metastatic colorectal cancer.

Authors: Angelique Vienot, Stefano Kim, Elodie Klajer, Dewi Vernerey, François Ghiringhelli, Christophe Tournigand, Romain Cohen, Stéphanie Husson, Jérôme Desrame, Jean-Baptiste Bachet, Asmahane Benmaziane, Emilie Soularue, Olivier Bouche, Claire Gallois, Eric Assenat, Aurelia Meurisse, Magali Rebucci-Peixoto, Christophe Borg

Background: Angiogenesis is associated with tumor progression, and antiangiogenic molecules have become a cornerstone in the treatment of metastatic colorectal cancer (mCRC). Regorafenib is a multi-kinase inhibitor and is an effective option in 20-25% of heavily pre-treated patients (Grothey et al, Lancet 2013; Li et al, Lancet Oncol 2015). Other therapies target the tumoral micro-environment, as metronomic chemotherapy (CT), with continuous low dose administration of a cytotoxic agent. This allows an anti-tumor effect, an anti-angiogenic activity, a stimulation of the immune system, and a better tolerance. Our team conducted an early research program REPROGRAM-01 study (NCT04534218). 49 patients with mCRC previously exposed to conventional chemotherapies are enrolled and received regorafenib in combination with a multimodal CT including capecitabine, cyclophosphamide and aspirin. We showed that this combination is safe. A tumor necrosis was observed in most patients displaying liver metastases and lymph nodes. In second-line treatment, maintenance of VEGF inhibition with chemotherapy beyond disease progression has clinical benefits in patients with mCRC. However, the short PFS (<6 months) and the poor tumor response observed (below 6%) deserved further investigations (ML18147 and VELOUR trials). Following these clinico-biological observations, the REPROGRAM-02 study (NCT05462613) investigates the potential clinical interest of a sequential treatment strategy including an induction phase based on regorafenib and a multimodal CT combining capecitabine, cyclophosphamide and low-dose aspirin before initiation of chemotherapy in second-line treatment of mCRC patients.

Methods: This is a French multi-center open-label, randomized (2:1) clinical trial. Patients with mCRC in progression after a 1st of chemotherapy, receive either (i) regorafenib (REDOS schedule: 80 mg for week 1, 120 mg for week 2 and 160 mg for week 3 of the first cycle) in combination with CT (capecitabine 625mg/m2 twice daily and cyclophosphamide 50 mg daily) and low-dose aspirin (75 mg once daily) during 8 weeks as an induction therapy before chemotherapy initiation in the second-line, or (ii) the second line standard chemotherapy (FOLFOX or FOLFIRI with anti-VEGF until progression or unacceptable toxicity). The primary objective is to assess the best response rate during treatment period for the phase II and the overall survival for the phase III. Secondary endpoints are progression-free survival, disease control rate, health related quality of life, toxicity, and the evaluation of exploratory biomarkers. Assuming a significance level of 5% and a power of 80%, a sample size of 93 patients is needed for the phase II and 446 patients for the phase III. The enrollment is ongoing, 13 patients have already been recruited. Clinical trial information: NCT05462613.

Optimization of intra-peritoneal chemotherapy: Randomized phase II GERCOR CHIMOVIP study.

Authors: Romain Cohen, Nadia Raban, Dewi Vernerey, Cyrille Huchon, Cédric Nadeau, Delphine Cochereau, Marie-Line Garcia-Larnicol, Ida Iurisci, Elisabeth Carola, Marie Fourreau, Antoine Falcoz, Richard Villet, Aimery De Gramont

Background: Upon initiation, our study built on three phase III studies indicating a significant increase in long-term overall survival (OS) with intraperitoneal (IP) chemotherapy. These trials incorporated patients with macroscopic residual disease (RD) <1cm. We hypothesized higher efficacy when administering IP chemotherapy early to patients achieving total completeness of cytoreduction (CC0) either at first surgery or at interval surgery (<3 months), and that pathological complete response (pCR) a surrogate of cure and OS. Cisplatin, the platinum salt recommended for IP administration of chemotherapy, was administered with epirubicin, chosen over paclitaxel to prevent neuropathy. To avoid potential biases, a control group, treated with conventional IV carboplatin and paclitaxel and undergoing the same surgical procedures, was included.

Methods: Eligible patients were aged <75 years and had epithelial ovarian cancer stage III or IV (pleura and lymph node only).In both arms patients had initial surgery and interval surgery after 3 chemotherapy cycles in the presence of residual disease. A second-look procedure was performed after 6 cycles in all CC0 patients. The IP arm, patients with CC0 at the first surgery received 6 cycles of IP cisplatin 80 mg/m² and intravenous (IV) epirubicin 60 mg/m². Those with RD at first surgery received 3 IV cycles of cisplatin-epirubicin, followed by 3 IP cycles of cisplatin and IV epirubicin in if CC0 was achieved at interval laparotomy. In the control arm patients received 6 cycles of IV carboplatin AUC6 with paclitaxel 80 mg/m² IV on days 1, 8, and 15. The primary endpoint was pathological complete response (pCR) rate. A Simon’s two stage design with an interim analysis planned after the inclusion of 18 evaluable patients in the experimental arm was used to test the following hypotheses: H0: a pCR rate of ≤ 20% (uninteresting) and H1: a pCR rate of ≥ 40% (expected).

Results: A total of 43 patients were randomized; 21 in the experimental IP arm and 22 in the control arm. At the interim analysis, 12 patients (66.7%) in the experimental arm and 11 (61.1%) in the control arm had pCR. A significant imbalance favoring the standard arm was observed for age, preoperative HE4, and low-grade tumor. There was no safety issue, with grade 3-4 toxicities lower in the IP arm (31.6% vs. 55.5% in the standard arm). With a median follow-up of 4.6 years 95%CI (4.2-5.0), median event free survival (EFS) and OS were respectively 3.0 years and not reached in the IP arm and 1.4 years and 3.5 years respectively in the IV arm (Table below).

Conclusions: While both arms showed ahigh pCR rate, EFS suggests that pCR is not a good surrogate for OS. The observed benefits in EFS and OS in the IP arm suggest a greater advantage of IP for CC0 patients. Clinical trial information: NCT03025477

NR: not reached, NE: not evaluable.

A propos de Sophie PAGET-BAILLY

Sophie Paget-Bailly is a research engineer in epidemiology and clinical research. She passed with honours the East of France inter-region master’s degree in public health and occupational and environmental risks. During the master’s degree’s internship in the Interregional Epidemiology Unit of Bourgogne/Franche-Comté, she realized a quantitative health risk assessment in the context of chemical contamination of groundwater. She defended a PhD in Public Health and Epidemiology in Paris XI University, Doctoral School 420, working in the Centre for Research in Epidemiology and Population Health in Villejuif, France. During her PhD, she worked on occupational exposures and head and neck cancer, providing two systematic reviews and meta-analyses and analyzing data from the ICARE case-control study. She was also representative of the PhD students at the ED420 school council.

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