Thursday, Aug 7: 10:30 AM - 12:20 PM
0417
Invited Paper Session
Music City Center
Room: CC-101B
Combination therapy is a critical treatment approach across many disease settings, including cancer, cardiovascular diseases, and infectious diseases. For instance, in solid tumors, perioperative regimens often include a combination of neoadjuvant therapy, surgery, and adjuvant therapy. Similarly, in hematological malignancies, maintenance therapy is frequently administered following induction or consolidation therapies. However, the question remains: is more always better, or could less be more?
Patients may face overtreatment, increased toxicity, and unnecessary burdens if the contribution of each therapy component is not well understood. This uncertainty raises the issue of whether every patient truly needs each component of a combination therapy. At a recent FDA Oncologic Drugs Advisory Committee meeting on July 25, 2024, regarding the durvalumab perioperative regimen, the agency voiced concerns about the necessity of both treatment phases. The committee unanimously recommended that new trial designs for perioperative regimens in resectable NSCLC should adequately assess the contribution of each treatment phase.
This raises a critical question: how should we design trials to isolate the contribution of each component effectively? Possible approaches include re-randomizing treatment arms, adding additional arms, utilizing external data sources, or other innovative methodologies. In time to event analyses, the evaluation of the treatment effect in such designs with treatment sequence is also quite challenging when intercurrent events are present. Our session will explore and discuss the latest developments in evaluating the effects of individual components within combination regimens.
Applied
Yes
Main Sponsor
Biopharmaceutical Section
Co Sponsors
Biometrics Section
ENAR
Presentations
The design and interpretation of oncology clinical trials increasingly recognize the importance of evaluating the contribution of different treatment phases, such as induction, consolidation, and maintenance to overall clinical benefit. Each phase may differentially impact key efficacy endpoints, including response rate, progression-free survival, and overall survival. However, traditional trial designs often aggregate outcomes across all phases, obscuring the individual effects of each treatment period.
In parallel, the rapid rise of combination therapies reflects the complexity of cancer biology and the ongoing challenge of potential overtreatment. Whether pairing two approved agents, adding a novel drug to an established backbone, or co-developing dual novel therapies, these regimens have become central to modern cancer treatment. Regulatory agencies such as the FDA and EMA increasingly require clear evidence of each phase and each individual component's contribution, demonstrating how each drug or phase affects the disease, how interactions occur, and whether every component provides meaningful clinical benefit without disproportionate risk or potential overtreatment.
Isolating these effects has become difficult and, in some cases, requires large sample sizes that may not be feasible. This presentation will examine statistical and design considerations across a range of trial settings, addressing the contribution of effect in combination therapies and different treatment phases, outlining strategies for generating confirmatory evidence, and highlighting practical challenges and emerging solutions through examples from recent oncology trials.
As oncology treatment regimens become increasingly sophisticated, isolating the contribution of each component is critical for regulatory approval and clinical application. This talk explores the regulatory landscape for developing new treatments with multiple components and phases, using AstraZeneca's AEGEAN ODAC as an example.
We highlight key regulatory guidelines that require clear evidence of each treatment's impact on efficacy and safety and discuss strategies to meet these requirements. The presentation discusses how AEGEAN ODAC integrates analytical approaches with regulatory compliance to inform personalized cancer treatment strategies. Attendees will gain insights into designing oncology trials that effectively isolate and address the contribution of each treatment effect within regulatory frameworks.