P-VERIFY: the largest real-world comparative overall survival analysis of first-line CDK4/6 inhibitors + AI in HR+/HER2- mBC to date.
P-VERIFY is the largest cross-CDK4/6 inhibitor analysis to date; it was a real-world, retrospective cohort analysis of electronic health records within the US Flatiron Health database.* Of 9146 patients who were eligible for this analysis, 6831, 1279 and 1036 patients received treatment with IBRANCE® + AI, ribociclib + AI and abemaciclib + AI, respectively.
The primary endpoint of the analysis was OS.† Unadjusted analyses were conducted first, and sIPTW was performed for the primary analysis to balance baseline demographics and clinical characteristics.‡
P-VERIFY showed no significant differences in overall survival between IBRANCE®, Ribociclib and Abemaciclib + AI in first-line HR+/HER2- mBC§¶
In the adjusted analysis, there were no significant differences in OS between treatment groups. Sensitivity analyses, using a multivariable Cox proportional-hazards regression model, also showed no significant differences in OS between treatment groups.
ESMO mBC Living Guidelines
The results of this analysis are in line with the current ESMO mBC Living Guidelines, which state that while there have been no head-to-head comparisons of the three approved CDK4/6 inhibitors, the efficacy of the three drugs in the metastatic setting appears similar.2,3 The toxicity profiles of these three drugs are slightly different and patients who develop a severe toxicity characteristic of one CDK4/6 inhibitor may switch to a different one.
No safety data was available from P-VERIFY. The overall safety profile of IBRANCE® is based on pooled data from 872 patients who received IBRANCE® in combination with endocrine therapy (n=527 in combination with letrozole and n=345 in combination with fulvestrant) in randomised clinical studies in HR+ HER2- advanced breast cancer or mBC. The most common (≥20%) adverse reactions of any grade reported in patients receiving IBRANCE® in randomised clinical studies were neutropenia, infections, leukopenia, fatigue, nausea, stomatitis, anaemia, diarrhoea, alopecia and thrombocytopenia.4 For full safety information, please refer to the IBRANCE® Summary of Product Characteristics.
* As this was a retrospective analysis of electronic health records, there was potential for treatment selection bias and inaccurate/incomplete data capture. Findings may not be generalisable to patient populations not represented in the Flatiron database;1 †OS was defined as the number of months from start of index treatment to death. Patients still alive were censored at the study cutoff date (May 31, 2024).Date of death was a consensus mortality endpoint based on electronic health records, Social Security Death Index, and obituary data, which has been validated against the National Death Index;1 ‡While sIPTW and multivariable analyses were used to balance baseline characteristics, unmeasured confounders cannot be addressed through these methods;1 §OS was a secondary endpoint in all 3 pivotal first-line CDK4/6 inhibitor randomised control trials in HR+/HER2- mBC. IBRANCE® + letrozole did not show a statistically significant OS difference in PALOMA-2. Abemaciclib + AI did not show a statistically significant OS difference in MONARCH-3. Ribociclib + letrozole demonstrated a statistically significant OS difference in MONALEESA-2;5–7 ¶Median duration of follow-up in IBRANCE®, abemaciclib, and ribociclib groups was 33 months, 15.7 months, and 21.5 months, respectively, with 45.3%, 25.6%, and 28% of deaths observed, respectively.
AI, aromatase inhibitor; CDK4/6, cyclin-dependent kinase 4/6; CI, confidence interval; ESMO, European Society for Medical Oncology; HER2, human epidermal growth factor receptor 2 negative; HR+, hormone receptor positive; HR, hazard ratio; mBC, metastatic breast cancer; OS, overall survival; sIPTW, stabilised inverse probability treatment weighting.
To learn more about the P-VERIFY analysis, download the poster here
References:
- Rugo HS, et al. SABC 2024. Poster PS2-03;
- Gennari A, et al. Ann Oncol 2021;32(12):1475–1495;
- ESMO. Metastatic Breast Cancer Living Guidelines, v1.1 May 2023. Available from: https://www.esmo.org/living-guidelines/esmo-metastatic-breast-cancer living-guideline/er-positiveher2- negative-breast-cancer. Accessed December 2024;
- IBRANCE® SmPC;
- Slamon DJ, et al. J Clin Oncol 2024;42(9):994–1000;
- Goetz MP, et al. Ann Oncol 2024;35(8):718–727;
- Hortobagyi GN, et al. N Engl J Med 2022;386(10):942–950.
SOURCE: https://www.pfizerpro.ie/medicine/ibrance/rwe/p-verify
