Investigators found in both trials that patients receiving first-line therapy with an aromatase inhibitor (AI) plus CDK4/6i, switching from AI to SERDs (fulvestrant in PADA-1 and camizestrant in SERENA-6) at ESR1 mutations detection before tumor progression while continuing CDK4/6 inhibition, resulted in significantly longer PFS compared to continuing AI (11.9 (95 % CI: 9.1–13.6) vs 5.7 months (95 % CI: 3.9–7.5)) in PADA-1 (HR 0.61, 95 % CI: 0.43–0.86, p = 0.0040) and 16.0 (95 % CI: 12.7–18.2) vs 9.2 months (95 % CI: 7.2–9.5) in SERENA-6 (HR 0.44, 95 % CI [0.31–0.60]; p < 0.0001)) [47,48]. The gene discussed is CDK4; the disease is neoplasm.