Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial
Mené en Chine sur 406 patients atteints d'un carcinome du rhinopharynx de stade localement avancé, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans échec, et la toxicité d'une chimiothérapie adjuvante métronomique par capécitabine
Background : Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk ofdisease relapse, despite a high proportion of patients attaining complete clinicalremission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapywith or without induction chemotherapy). Additional adjuvant therapies are neededto further reduce the risk of recurrence and death. However, the benefit of adjuvantchemotherapy for nasopharyngeal carcinoma remains controversial, highlighting theneed for more effective adjuvant treatment options.
Methods : This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trialwas done at 14 hospitals in China. Patients (aged 18–65 years) with histologicallyconfirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III–IVA,excluding T3–4N0 and T3N1 disease), no locoregional disease or distant metastasisafter definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performancestatus of 0 or 1, sufficient haematological, renal, and hepatic function, and whohad received their final radiotherapy dose 12–16 weeks before randomisation, wererandomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation(standard therapy group). Randomisation was done with a computer-generated sequence(block size of four), stratified by trial centre and receipt of induction chemotherapy(yes or no). The primary endpoint was failure-free survival, defined as the time fromrandomisation to disease recurrence (distant metastasis or locoregional recurrence)or death due to any cause, in the intention-to-treat population. Safety was assessedin all patients who received at least one dose of capecitabine or who had commencedobservation. This trial is registered with ClinicalTrials.gov, NCT02958111.
Findings : Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 wereenrolled and randomly assigned to the metronomic capecitabine group (n=204) or tothe standard therapy group (n=202). After a median follow-up of 38 months (IQR 33–42),there were 29 (14%) events of recurrence or death in the metronomic capecitabine groupand 53 (26%) events of recurrence or death in the standard therapy group. Failure-freesurvival at 3 years was significantly higher in the metronomic capecitabine group(85·3% [95% CI 80·4–90·6]) than in the standard therapy group (75·7% [69·9–81·9]),with a stratified hazard ratio of 0·50 (95% CI 0·32–0·79; p=0·0023). Grade 3 adverseevents were reported in 35 (17%) of 201 patients in the metronomic capecitabine groupand in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome wasthe most common adverse event related to capecitabine (18 [9%] patients had grade3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group hadgrade 4 neutropenia. No treatment-related deaths were reported in either group.
Interpretation : The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantlyimproved failure-free survival in patients with high-risk locoregionally advancednasopharyngeal carcinoma, with a manageable safety profile. These results supporta potential role for metronomic chemotherapy as an adjuvant therapy in the treatmentof nasopharyngeal carcinoma.
The Lancet , résumé, 2020