BENCHMARKING TO ESTABLISH PERSPECTIVE: 36-MONTH RMST GAIN IN HR+, HER2- METASTATIC BREAST CANCER
Author(s)
Aino Launonen, MSc1, Margaux Vittori, MSc2, Ioana-Alexandra Soare, MSc3, Luisa Maria Alves Queiros, MSc3.
1Access evidence Lead, Roche, Basel, Switzerland, 2Roche, Paris, France, 3Roche, Basel, Switzerland.
1Access evidence Lead, Roche, Basel, Switzerland, 2Roche, Paris, France, 3Roche, Basel, Switzerland.
OBJECTIVES: European health technology assessment (HTA) frameworks, including the methodological annexes for Haute Autorité de Santé (HAS) evaluation, are paying increased attention to Restricted Mean Survival Time (RMST) to assess oncology treatments. This study benchmarks the 36-month Overall Survival (OS) RMST gain in the INAVO120 trial against historical landmark trials in HR+, HER2− mBC.
METHODS: Published OS Kaplan-Meier curves from relevant clinical trials (MONALEESA-3; MONARCH-2; PALOMA-3) were digitized. Within-study treatment differences in 36-month OS RMST and median were estimated, and parametric survival functions were fitted on the INAVO120 OS data.
RESULTS: While adding the CDK4/6 inhibitors (i) to fulvestrant yielded notable median OS gains, the 36-month OS RMST benefits were remarkably small with confidence intervals (CI) crossing zero: MONALEESA-3 (median: 10.7 months; RMST: 1.4 months [95% CI: -0.1, 3.0]), MONARCH-2 (median: 8.5 months; RMST: 0.7 months [95% CI: -1.0, 2.5]), and PALOMA-3 (median: 6.8 months; RMST: 1.6 months [95% CI: -0.5, 3.7]). INAVO120 demonstrated a median OS benefit of 7.0 months, while ad-hoc analysis showed a 36-month RMST gain of 2.9 months (95% CI: 0.2, 5.5). Clinically-validated parametric extrapolations yielded a lifetime mean OS gain of 6.2 months for Itovebi in PIK3CA-mutated 1L HR+, HER2− mBC across 46 years.
CONCLUSIONS: Lacking formalized criteria for meaningful RMST difference, empirical benchmarking is required to interpret its clinical value and ultimately support HTA assessments. While absolute RMST and median gains are sensitive to baseline survival, our results provide an essential perspective. Historically, 36-month OS RMST gains in mBC are moderate: 0.7-1.6 months when adding a CDK4/6i to fulvestrant. However, adding Itovebi to CDK4/6i+fulvestrant increased this further by 2.9 months. The contrast between a 36-month restricted evaluation and the extrapolated lifetime mean gain of 6.2 months for Itovebi illustrates that survival benefits are distributed across patients’ lives rather than captured entirely within restricted early windows
METHODS: Published OS Kaplan-Meier curves from relevant clinical trials (MONALEESA-3; MONARCH-2; PALOMA-3) were digitized. Within-study treatment differences in 36-month OS RMST and median were estimated, and parametric survival functions were fitted on the INAVO120 OS data.
RESULTS: While adding the CDK4/6 inhibitors (i) to fulvestrant yielded notable median OS gains, the 36-month OS RMST benefits were remarkably small with confidence intervals (CI) crossing zero: MONALEESA-3 (median: 10.7 months; RMST: 1.4 months [95% CI: -0.1, 3.0]), MONARCH-2 (median: 8.5 months; RMST: 0.7 months [95% CI: -1.0, 2.5]), and PALOMA-3 (median: 6.8 months; RMST: 1.6 months [95% CI: -0.5, 3.7]). INAVO120 demonstrated a median OS benefit of 7.0 months, while ad-hoc analysis showed a 36-month RMST gain of 2.9 months (95% CI: 0.2, 5.5). Clinically-validated parametric extrapolations yielded a lifetime mean OS gain of 6.2 months for Itovebi in PIK3CA-mutated 1L HR+, HER2− mBC across 46 years.
CONCLUSIONS: Lacking formalized criteria for meaningful RMST difference, empirical benchmarking is required to interpret its clinical value and ultimately support HTA assessments. While absolute RMST and median gains are sensitive to baseline survival, our results provide an essential perspective. Historically, 36-month OS RMST gains in mBC are moderate: 0.7-1.6 months when adding a CDK4/6i to fulvestrant. However, adding Itovebi to CDK4/6i+fulvestrant increased this further by 2.9 months. The contrast between a 36-month restricted evaluation and the extrapolated lifetime mean gain of 6.2 months for Itovebi illustrates that survival benefits are distributed across patients’ lives rather than captured entirely within restricted early windows
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO113
Topic
Clinical Outcomes, Health Technology Assessment, Methodological & Statistical Research
Topic Subcategory
Relating Intermediate to Long-term Outcomes
Disease
Oncology