Presentation (CTI)

OBJECTIVES: In early cancer, new treatments may be administered prior to surgery (neoadjuvant), after surgery (adjuvant) or across both settings (perioperative). Without head-to-head studies, the comparative efficacy of these strategies must be estimated via indirect treatment comparison (ITC). Using a case study, we highlight the challenges of using standard ITC methodologies in comparing perioperative with adjuvant strategies and propose an alternative methodology.
METHODS: Following guidelines, we consider the feasibility of performing anchored or unanchored ITCs in a case study involving a (study 1) ‘perioperative’ study of drug A plus neoadjuvant therapy versus neoadjuvant therapy followed by best supportive care (BSC) and (study 2) an ‘adjuvant’ study of drug B versus BSC. An alternative survival-time adjusted approach using a counterfactual survival time (CST) methodology is proposed and its benefits and limitations are described.
RESULTS: Differences in randomisation times, trial eligibility, and control treatments are expected to invalidate the exchangeability assumption of standard anchored ITCs. Unanchored ITCs typically require overlap in populations limiting comparisons to the adjuvant phase and excluding relevant neoadjuvant outcomes. Using CST methodology, the ‘adjuvant’ survival times of eligible patients in the control arm of the ‘perioperative’ study are adjusted for the effects of adjuvant drug B using acceleration factors derived from the ‘adjuvant’ study. This yields a counterfactual arm representing outcomes for neoadjuvant therapy followed by ‘adjuvant’ drug B. The effects of perioperative drug A versus neoadjuvant therapy followed by drug B are estimated by comparing the ‘perioperative’ and counterfactual arms. Randomisation in the ‘perioperative’ study supports baseline comparability between arms, whilst randomisation in the adjuvant study supports estimation of the drug B effect. Key limitations include the assumption of exchangeable treatment effects across studies.
CONCLUSIONS: CST methods provide a promising approach to comparing between phases of treatment, where the assumptions underpinning standard ITC methods are unlikely to hold.