Predictive factors for early progression during induction chemotherapy and chemotherapy-free interval: analysis from PRODIGE 9 trial

• Published in: British journal of cancer 2020-03, Vol.122 (7), p.957-962
• Main Authors: Aparicio, Thomas, Bennouna, Jaafar, Le Malicot, Karine, Boige, Valérie, Taieb, Julien, Bouché, Olivier, Phelip, Jean-Marc, François, Eric, Borel, Christian, Faroux, Roger, Dahan, Laetitia, Bachet, Jean-Baptiste, Egreteau, Joelle, Kaminsky, Marie-Christine, Gornet, Jean-Marc, Cojocarasu, Oana, Gasmi, Mohamed, Guerin-Meyer, Véronique, Lepage, Côme, Ghiringhelli, François
• Format: Article
• Language: English
• Subjects: 631/67/1504/1885; 692/53/2422; Aged; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chemotherapy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Disease Progression; Drug Resistance; Epidemiology; Female; Humans; Induction Chemotherapy - methods; Leukocytes; Male; Metastases; Molecular Medicine; Multivariate analysis; Mutation; Oncology; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-020-0735-8

Background Identifying patients with metastatic colorectal cancer who will have an early disease progression during induction chemotherapy (IC) and identifying patients who may have a chemotherapy-free interval (CFI) after IC are two major challenges. Methods A logistic model was used to identify factors associated with early progression during IC and with short duration of the first CFI in 488 patients enrolled in the PRODIGE 9 trial. Independent factors were defined with a threshold 0.10. Results In multivariate analysis, baseline leukocytes >10 × 10 9 /L (OR = 1.98 [1.02–3.8], p  = 0.04), and stable or increasing CEA at 2 months (OR = 3.61 [1.68–7.75], p  = 0.01) were independent factors associated with progression during IC. Male gender (OR = 1.725 [0.92–3.325], p  = 0.09) and no tumour response at first evaluation (OR = 1.90 [0.96–3.76], p  = 0.07) were significantly associated with a short CFI. The presence of BRAF V600E mutation was also associated with short CFI (OR = 4.59 [0.95; 22.3], p  = 0.058). Conclusion High baseline leukocyte count and the lack of CEA decrease level at first evaluation were associated with early progression, and could be in favour of early chemotherapy intensification. Male gender, no tumour response at first evaluation and BRAF mutation are associated with a short CFI, and may be considered for maintenance chemotherapy after IC. Clinical trial number NCT00952029.