Armando Orlandi: The Underutilized POETIC Trial Results

Armando Orlandi, Medical Director at the Agostino Gemelli University Hospital Foundation IRCCS, shared a post on LinkedIn about a paper by Milana Bergamino Sirvén et al. published in eBioMedicine:

“Why Are We Ignoring Game-Changing Evidence? The Underutilized POETIC Trial Results

The original POETIC trial results, published in Lancet Oncology in 2020, demonstrated something revolutionary: 2 weeks of preoperative endocrine therapy could predict long-term outcomes in hormone-positive breast cancer. Yet, this evidence has been inexplicably underutilized in clinical practice.

What POETIC Showed Us:

• Ki67 response after just 14 days of aromatase inhibitors predicted 5-year outcomes
• Simple, cost-effective biomarker assessment with profound prognostic value
• Potential to personalize treatment decisions from day one

Now, This New Translational Analysis Reinforces:

• 79% of Luminal B tumors convert to Luminal A in ER+/HER2+ patients
• On-treatment Luminal A status = 80% reduction in recurrence risk
• Molecular profiling at 2 weeks outperforms baseline parameters

The Genomic Signature Paradox:

Ironically, while we waited years for OncotypeDx and Prosigna to gain widespread adoption (despite their robust validation), we’ve overlooked a dynamic, real-time approach that could complement these static baseline assessments. These genomic signatures, though valuable, only capture a tumor’s baseline biology—not its functional response to therapy.

The New Clinical Reality:

Today’s landscape is further complicated by adjuvant CDK4/6 inhibitors entering standard practice. How do we integrate:

• Baseline genomic risk scores
• Dynamic endocrine response assessment
• CDK4/6 inhibitor candidacy
• Treatment de-escalation opportunities?

Enter ADAPT-Cycle: The Missing Link?

The ADAPT-Cycle trial may finally provide the framework we need—combining:

• Window-of-opportunity endocrine response assessment
• Genomic risk stratification
• Rational CDK4/6 inhibitor selection
• Evidence-based treatment personalization

The Critical Question:

Why do we excel at generating evidence but struggle with implementation science? We have:

• Evidence: Strong, published in top-tier journals
• Biology: Sound mechanistic rationale
• Tools: Available and validated
• Integration: Fragmented, specialty-dependent adoption

The Reality Check:

We cannot afford to let perfect be the enemy of good. While we debate optimal integration strategies, patients receive treatment based on increasingly outdated paradigms.

Call to Action:

The convergence of dynamic response assessment, genomic profiling, and targeted therapy selection represents the future of precision oncology. ADAPT-Cycle and similar trials may finally provide the roadmap for implementing what POETIC taught us years ago.

Our patients deserve treatment decisions based on their tumor’s actual behavior, not just its baseline characteristics.”

Title: Short-duration preoperative endocrine therapy alters molecular profiles to predict favourable outcome in ER+/HER2+ early breast cancer: a POETIC translational study

Authors: Milana Bergamino Sirvén, Elena López-Knowles, Xixuan Zhu, Holly Tovey, Lucy Kilburn, Chris Holcombe, Anthony Skene, John Robertson, Judith M. Bliss, Anastasia Alataki, Ian Smith, Eugene F. Schuster, Mitch Dowsett, Maggie Chon U. Cheang.

You can read the Full Article in eBioMedicine.

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