The findings of this study suggest that patients receiving palbociclib in the combination with fulvestrant as second or later lines had good tolerance, with low rates of treatment discontinuation due to adverse effects (including neutropenia) and dose-adjustment. A clinical benefit rate of 66.6% was identified, and progression-free survival at 12 months was 0.69 (95% CI 0.58–0.82).
Results were similar to PALOMA-3 in terms of clinical benefit rate, with high levels of PFS at 12 months. However, the objective response rate was lower than that communicated in the pivotal trial, and better in terms of PFS. Whilst the median was not reached at the end of the follow up, Paloma-3 study reported a median of 9.5 months12. PFS at 12 months observed in this Colombian population were more favorable than other real-world studies, where the median of PFS was achieved before 12 months or the value was lower than 0.60 at this time point20,21. In terms of progression rate, similar results were obtained in other studies conducted in Europe and US, with a progression rate of approximately 21%22–24. Results were better in Argentina, with a 6% less progression rate than the Colombian population13. The overall survival reported in this study was favorable with only one death reported by progression during the 12 months of follow-up.
Early discontinuation leads to greater recurrence rates and negatively influences survival25. The discontinuation rate was variable in observational studies, which vary greatly in other studies. For instance, patients in Hungary treated with palbociclib had a discontinuation rate of 56.0% at 12 months while 49.6% of patients switched to other therapies26. In other studies, a 72.2% discontinuation rate was reported among patients in Spain19, while in the US this was 19.9% 24 and in Argentina, 2.0%13. In the case of Colombia, the health care system is obliged to guarantee the treatment after approval by the HMO, thus the present study shows that discontinuation was more associated with progression of the disease and safety causes than administrative issues related to insurance.
In the present study high levels of delays in the patients’ treatment were seen, with 89% reporting at least one delay during follow up. Other countries such as Argentina and the US reported rates of delays of 11% and 15%, respectively13,24. Therefore, local authorities need to continue working to guarantee adequate access to these treatments, particularly for time-sensitive disorders such as breast cancer.
Tolerability was consistent between the pivotal trial and other real-world studies, which reported discontinuation due to adverse events in 4% of the patients12,13,27. However, the number of serious adverse events were smaller in this study than other reports, including PALOMA-3. Similar to the other studies, neutropenia was the main adverse event19,23, and dose modifications or transitory suspension were required in some patients.
Strengths of this study include the definitions of outcomes, PFS and OS, which were obtained from routine clinical data, as they were reported in the medical records. The study is also bringing a wider perspective, providing evidence among different cancer care sites across the country. However, these findings may not be generalizable to the overall advanced breast cancer population in Colombia despite the representation of the different sites, since the sample size was small to the expected. There were limited number of patients available in the index period, mainly, for Palbociclib was recently commercialized in the index period having administrative issues with HMOs. Likewise, for the limited sample size, statistical analyses for some subgroups of patients were not conducted.
Immortal bias was not identified for the inclusion criterion of minimum time of treatment with two months due to none patient was excluded by this criterion. Other limitations include the observational nature of the study, and the lack of a control group. Although the assessment of disease progression was evaluated through imaging procedures, physical exams, assessment of symptoms, or other methods, according to definitions used in previous published studies, the measurement of PFS has a combination of subjective and objective variables, contrary to overall survival, reducing the reliability of the outcome.
The landscape of breast cancer continues to evolve, as implementation of novel strategies in health care delivery and new treatments for breast cancer emerge for the Colombian population. This new evidence for treatment patterns and outcomes provides critical information supporting clinician assessment of treatments for patients and provides further insight into local clinical practice. In the next few years, long-term data in clinical outcomes will be needed especially in different groups of patients, to recognize changes in disease patterns and access to treatments.