Leveraging existing data to contextualize phase II clinical trial findings in oncology
- In the USA, over 250,000 women are diagnosed with early-stage breast cancer (EBC) yearly, with up to 30% having HER2 amplification.
- The standard care for HER2-positive EBC involves chemotherapy plus HER2-directed therapy for one year.
- The phase II Adjuvant Paclitaxel and Trastuzumab (APT) trial suggests that patients with small HER2+ tumors might achieve favorable outcomes with paclitaxel and trastuzumab alone, avoiding multi-agent chemotherapy toxicity.
- Limitations of phase II trials include lack of comparison arms and insufficient power to draw firm conclusions, while phase III trials face issues of feasibility and cost.
- Amiri-Kordestani and colleagues used pooled historical clinical trial data to address phase II APT trial limitations by creating an external control arm for comparison.
- Similar invasive disease-free survival (iDFS) and overall survival (OS) at 3 and 5 years were observed between ACTH/TCH and TH arms.
- Cross-trial comparisons are challenging due to different populations and lack of randomization, but propensity score matching helps address measurable confounders.
- Time-trend bias is a limitation, but improvements in clinical care are unlikely to have varied significantly during the study period.
- Real-world data like EHR-derived datasets could provide additional context for phase II findings, but current limitations include incomplete clinical information.
- The FDA aims to advance real-world data into regulatory-quality evidence, and initiatives like mCODE™ seek to standardize oncology data.
- Amiri-Kordestani's study shows that using historical data to contextualize phase II findings can be effective, especially for de-escalation therapies.
- This method could improve clinical trial accrual and patient access to new therapies, demonstrating the FDA's commitment to leveraging existing data.
- While large randomized trials are crucial, comparative studies using existing data offer timely and affordable contributions to clinical oncology.
More than 250 000 women are diagnosed with early-stage breast cancer (EBC) in the USA each year. Of these, up to 30% have amplification of the human epidermal growth factor 2 (HER2).2 The current standard of care for HER- positive (HER2þ) EBC is chemotherapy plus HER2-directed therapy to complete 1 year of treatment. There is growing interest in determining which patients with HER2þ tumors could achieve favorable outcomes with less chemotherapy through better HER2-targeting. The phase II Adjuvant Paclitaxel and Trastuzumab (APT) trial by Tolaney and colleagues provided compelling evidence that patients with small HER2þ tumors without nodal macro-metastases can achieve highly favorable outcomes with paclitaxel and trastuzumab alone (TH), avoiding the toxicity associated with multi-agent chemotherapy regimens. Use of TH in this context has been widely adopted in the clinical setting despite the lack of a confirmatory phase III trial.
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