Radiation vs. Trans-Oral Surgery for Treatment De-Escalation in HPV-Related Oropharyngeal Cancers: Primary Analysis of the ORATOR2 Randomized Trial
Mené sur 61 patients atteints d'un carcinome épidermoïde oropharyngé lié au HPV (âge médian : 62 ans ; durée médiane de suivi : 3,7 ans), cet essai randomisé compare l'efficacité, du point de vue de la survie globale à 2 ans, de 2 stratégies de désescalade (radiothérapie primaire ou chirurgie transorale)
Background: The optimal treatment de-escalation approach for HPV-related oropharyngeal squamous cell carcinomas (OPSCC) is unknown. The objective was to assess two de-escalation approaches: primary radiotherapy (RT) vs. transoral surgical (TOS).
Patients and Methods: Patients with T1-T2 N0-2 HPV-related OPSCC were randomly assigned to primary RT (60 Gy with concurrent weekly cisplatin in node-positive) vs. TOS + neck dissection (ND) (and adjuvant reduced-dose RT depending on pathology). The primary endpoint was 2-year OS (hypothesized to be 94% in each arm, compared to 84%). Secondary endpoints included comparisons of survival and quality of life between arms. The trial was stopped early due to two treatment related deaths in the surgical arm.
Results: Sixty-one patients were randomized (n=30 in RT arm and n=31 in TOS+ND arm), with a median age of 62 years (IQR: 57-68). The majority were male (n=51) and never-smokers (n=31). Median follow-up was 3.7 years (IQR: 3.1-4.5 years). In the RT arm, the primary endpoint for acceptability was met (p=0.008), and two-year OS was 100% (95% confidence interval [CI]: 100-100%). In the TOS+ND arm, the primary endpoint was not met (p=0.296) and two-year OS was 90% (95% CI: 71-97%), significantly worse than the RT arm (p=0.041). Two-year progression-free survival (PFS) were 100% (95% CI: 100-100%) vs. 86% (95% CI: 67-95%) respectively (p=0.012). Mean (±SD) 2-year MDADI total scores were 89±13 vs. 83±11, respectively (p=0.11), and grade 2-5 toxicity rates were similar (n=21 vs. n=24 respectively, p=0.51), with no additional grade 5 events.
Conclusion: For treatment de-escalation, a primary RT approach achieved excellent oncologic and functional outcomes and should be tested in phase III de-escalation trials.