Opinion

Armando Orlandi: Real-World Evidence vs. Head-to-Head Comparisons

Armando Orlandi/photos.asco.org

Sep 3, 2025, 18:01

Armando Orlandi: Real-World Evidence vs. Head-to-Head Comparisons

Armando Orlandi, Medical Director at the Agostino Gemelli University Hospital Foundation IRCCS, shared on LinkedIn:

“Real-World Evidence vs. Head-to-Head Comparisons: Lessons from CDK4/6 Inhibitor Studies

The recent publication of contrasting real-world studies on CDK4/6 inhibitors (PALMARES-2 vs. P-VERIFY) offers an important lesson for oncology research.

The Dilemma

PALMARES-2 (🇮🇹 study): Found significant differences favoring abemaciclib/ribociclib over palbociclib
P-VERIFY (🇺🇸 study): No significant differences between the three CDK4/6 inhibitors

The Issue

Despite sophisticated statistical adjustments (propensity scores, IPTW, multivariable analyses), observational studies cannot fully address selection bias and population heterogeneity when comparing active treatments.

The Solution

Real-world evidence should focus on its true strengths:

Validating efficacy in underrepresented populations
Long-term safety in diverse cohorts
Treatment patterns in clinical practice

Bottom Line

Let’s use RWE for what it does best – complementing RCTs by addressing questions trials can’t answer, rather than attempting inferior head-to-head comparisons.”

Title: Real-world progression-free survival of CDK4/6 inhibitors plus an aromatase inhibitor in HR-positive/HER2-negative metastatic breast cancer in United States routine clinical practice

Authors: H.S. Rugo, R.M. Layman, F. Lynce, X. Liu, B. Li, L. McRoy, A.B. Cohen, M. Estevez, G. Curigliano, A. Brufsky

Read the full article.

Armando Orlandi: Real-World Evidence vs. Head-to-Head Comparisons