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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.

P-VERIFY_SABC-POSTER_12-2024

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:

1. Rugo HS, et al. SABC 2024. Poster PS2-03;
2. Gennari A, et al. Ann Oncol 2021;32(12):1475–1495;
3. 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;
4. IBRANCE® SmPC;
5. Slamon DJ, et al. J Clin Oncol 2024;42(9):994–1000;
6. Goetz MP, et al. Ann Oncol 2024;35(8):718–727;
7. Hortobagyi GN, et al. N Engl J Med 2022;386(10):942–950.

SOURCE: https://www.pfizerpro.ie/medicine/ibrance/rwe/p-verify