Phase 3 RCT comparing docetaxel-platinum with docetaxel-platinum-5FU as neoadjuvant chemotherapy in borderline resectable oral cancer
Mené sur 495 patients atteints d'un cancer de la cavité buccale à la limite de la malignité et résécable, cet essai de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout de 5-fluorouracile à une chimiothérapie néoadjuvante à base de docétaxel et de cisplatine
Background: Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF. Methods: In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events. Results: 495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95%CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P=0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS were 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P<0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P<0.0001). Conclusion: NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival. Keywords