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The addendum of the ICH E9 guideline on the statistical principles for clinical trials introduced the estimand framework. The framework is designed to strengthen the dialog between different stakeholders, to introduce greater clarity in the clinical trial objectives and to provide alignment between the estimand and statistical analysis. Estimand framework related publications thus far have mainly focused on randomized clinical trials. The intention of the Early Development Estimand Nexus (EDEN), a task force of the cross‐industry Oncology Estimand Working Group (www.oncoestimand.org), is to apply it to single arms Phase 1b or Phase 2 trials designed to detect a treatment‐related efficacy signal, typically measured by objective response rate. Key recommendations regarding the estimand attributes include that in a single arm early clinical trial, the treatment attribute should start when the first dose is received by the participant. Focusing on the estimation of an absolute effect, the population‐level summary measure should reflect only the property used for the estimation. Another major component introduced in the ICH E9 addendum is the definition of intercurrent events and the associated possible ways to handle them. Different strategies reflect different clinical questions of interest that can be answered based on the journeys an individual subject can take during a trial. We provide detailed strategy recommendations for intercurrent events typically seen in early‐stage oncology. We highlight where implicit assumptions should be made transparent as whenever follow‐up is suspended, a while‐on‐treatment strategy is implied. [ABSTRACT FROM AUTHOR]

Objectives: The German‐speaking Myeloma Multicenter Group (GMMG) conducted this trial to investigate efficacy and safety of the three‐drug combination bendamustine/prednisone/bortezomib (BPV) as first‐line therapy for elderly patients with multiple myeloma (MM). Methods: Elderly MM patients requiring first‐line therapy and not eligible for intensive treatment were enrolled in this phase IIb multicenter study. Patients were treated with BPV regimen for a maximum of nine cycles. Results: Forty‐six patients were included in the trial with a median age of 76 years. Nineteen patients had renal impairment at baseline. The ORR was 78.8% for patients treated with 3 and more BPV cycles and 71.1% for all evaluable patients. The median progression‐free survival was 25 months, and overall survival at 24 months was 83.3%. The clinical benefit rate including MR was 91.2%. In patients with renal impairment at baseline, a renal response was observed in 11 pts. with complete recovery of the renal function in six patients. The most frequent CTC grade 3/4 AEs experienced by patients were hematological (17.5%) and infectious (9.8%) complications. No new safety signals were observed for the study drugs under investigation. Conclusions: Bendamustine/prednisone/bortezomib may serve as a first‐line regimen for transplant‐ineligible elderly MM patients in particular for patients with renal impairment requiring a fast and durable renal response. [ABSTRACT FROM AUTHOR]