Exploring Platinum-Based Treatment Realities: What do Real-World Data Reveal for the Management of Endometrial Cancer in Brazil? – the ECHOS-B Retrospective Study

Endometrial cancer (EC) is the sixth most prevalent cancer in women worldwide.1 In 2022, 420,368 new cases of EC were diagnosed worldwide, accounting for 97,723 deaths.2 In Brazil, 12,616 new cases of EC were diagnosed, accounting for 3,333 deaths in 2022.3 By 2050, the global incidence of EC is projected to increase by more than 60%, and, in Brazil, by more than 72%.4

The treatment recommendations for EC are typically driven by the grade and stage of the disease.5 Most patients with EC present with early-stage disease, for which surgery is the gold standard of care.5 6 Adjuvant radiation and vaginal brachytherapy are recommended for those with high-to-intermediate risk of recurrence.5 Systemic drugs/chemotherapy are reserved for the adjuvant treatment of stage-I and -II EC with a high risk of recurrence, the treatment of advanced disease (stages III/IV), or the treatment of recurrent disease.5 7 Importantly, the overall survival (OS) in EC decreases with more advanced disease stage at diagnosis.

The standard of care during the study period regarding the first-line therapy (1L) for advanced/relapsed EC was platinum-based therapy (PBT); however, the prognosis is poor, with limited duration of the benefits.7 A further challenge is that there is no standard of care, and the treatment options are limited for women with EC whose disease progresses during or after 1L with PBT.5 7 There is an urgent need for treatment approaches that prevent or delay EC progression beyond what is achievable with PBT to help improve patient outcomes. Since the study was conducted, other EC treatments gained approval in Brazil; however, their adoption and impact have yet to be assessed.8 9 10 11

There is a scarcity of real-world data regarding patient characteristics, treatment patterns, and clinical outcomes in women with EC, especially in Latin America.9 12 13 Real-world data enhances the understanding of disease burden and unmet treatment needs. Furthermore, within the private healthcare setting, measuring outcomes such as time until the first treatment may act as a proxy to service efficiency, and understanding factors such as the duration of the treatment and disease progression may support the planning and evaluation of EC care in Brazil.

Therefore, the Endometrial Cancer Health and Clinical Outcomes Study in Brazil (ECHOS-B) was conducted to describe real-world treatment patterns and outcomes in women with EC in Brazil who had received 1L with PBT in the private healthcare system.

Real-world data are lacking for patients with EC, especially in Latin American countries.9 12 13 To the best of our knowledge, the current is the first real-world study to describe the treatment patterns of Brazilian patients with EC (Supplementary Fig. S1 Visual Abstract (online only)).

In the present study, we analyzed data from 1,078 Brazilian women with private health insurance between 2015 and 2020. Most patients (70.0%) received 1L, more than 2/3 of whom (68.9%) received 1L with PBT. Almost 60% of the women treated with 1L with PBT were aged ≥ 60 years, which is indicative of a demographic considered at a high risk of developing EC.9 17 Among patients in ECHOS-B who received systemic therapy, more than half received the carboplatin/paclitaxel combination in 1L, which was in line with the guideline recommendations at the time.5 7 In a comparable retrospective study, the ECHOS-A,18 which was conducted in Argentina (an upper-middle-income economy) among patients diagnosed with EC who received 1L, most (74%) of the sample received 1L with PBT. Of these patients, 73% received 1L with the carboplatin/paclitaxel combination.18 Notably, real-world studies from high-income economies with similar methodologies have reported higher proportions of patients treated with 1L with PBT19 20 21 and high rates (range: 73–99%) of 1L carboplatin/paclitaxel treatment.18 19 20 22

All Brazilians are covered by public health insurance; in 2022, 25% of the population was also covered by private health insurance, which is considered to provide easier access to certain services or professionals.23 Our findings using the Orizon database, which covers 20% of the private healthcare system, may serve as a proxy to assess service efficiency in the private healthcare setting and may support improvements in the planning and evaluation of EC care in Brazil. Thus, efforts to gain a deeper understanding of the treatment patterns herein reported may help identify unmet medical needs and improve the outcomes for these patients in Brazil.

The prognosis of patients with EC has been shown to be correlated with delays in diagnosis and treatment initiation.24 Disparities regarding access to healthcare contribute to long delays between cancer diagnosis and first treatment.25 26 Despite the “Law of 60 days,” in the public healthcare setting, up to 38% of women with EC in Brazil wait more than 90 days for their first treatment.25 In addition, women often face more advanced disease and worse disease-free survival and OS compared with women treated in private healthcare facilities, likely due to longer delays and limited access to specialist facilities and high-cost drugs.8 26 27 Indeed, in the current study, in a private healthcare setting, we report the mean time from index date to first EC-related treatment of 2.5 ± 5.4 months. Similarly, in an observational study28 using public health data from a Brazilian hospital, among 185 patients with EC, the mean time from diagnosis to EC-related treatment was 131 ± 71 days, with only 12.1% of the patients beginning treatment within 60 days of the diagnosis.

Due to the paucity of real-world data on treatment patterns and outcomes for EC, comparisons of the patients submitted to 1L with PBT herein described with other real-world studies are challenging. Nonetheless, in the present study, the cumulative rwOS rates after 1L with PBT decreased over time, which was broadly consistent with trends observed in other real-world studies—albeit in patients with advanced/recurrent EC who received prior chemotherapy.20 29 30 It is worth noting that, within an administrative health claims study, as not all death events are captured, the outcomes related to death rates may be underestimated. The absence of disease stage from our dataset may pose limitations to the interpretation and evaluation of the treatment patterns herein reported regarding disease severity. Efforts to overcome the lack of clinical data on disease stage were made by evaluating patients receiving PBT, as they are typically diagnosed with advanced/recurrent disease.5 7

Currently, the treatment options for women with EC progressing after 1L are limited.5 Additionally, standard 2L chemotherapeutic options have not yet been clearly defined, as none have significantly improved patient outcomes to date,5 as evidenced by other real-world studies.19 20 21 In the current study, progression after 1L with PBT occurred in more than 2/5 (41.3%) of the patients, 1/5 of whom (19.5%) died, and more than 3/4 (80.5%) received another systemic treatment; none received radiotherapy or surgery in the 2L setting. In contrast, guidelines7 recommend adjuvant radiotherapy in patients with high-to-intermediate risk (with or without lymphovascular space invasion) and high risk of developing EC. Among the patients receiving 1L with PBT in the ECHOS-A,18 progression events were reported in more than 3/5 (63.7%), and approximately 3/5 of these patients (58.1%) received another systemic treatment, ∼ 10% underwent surgery (9.7%) or radiotherapy (12.9%), and almost 1/5 died (19.4%). In the current study, among patients receiving 1L with PBT, the risk of progression increased over time (1- to 5-year risk: 36.2–59.8%) with a median time until progression of 18.2 months. Similarly, in ECHOS-A,18 the progression risk increased over time, albeit with higher progression risk estimates observed across 5 years (46.5–77.5%), and a shorter median time until progression, of 12.9 months.

In the current study, a large proportion (60.7%) of patients who experienced progression received rechallenge with PBT. While there is no globally-accepted standard of care in the 2L, our data are consistent with those of other real-world studies,21 29 which reported similar findings for patients with EC receiving 1L with PBT who were rechallenged with 2L with PBT. In a retrospective study conducted in the United States29 using data on administrative claims between 2004 and 2019, almost 60% of the patients who had previously been submitted to 1L with PBT were retreated with 2L with PBT. Similarly, an analysis of patients with EC receiving 1L with PBT from Japan21 reported that more than 60% were retreated with 2L with PBT.

The EC treatment setting has altered markedly in recent years, and immune-oncology and chemotherapy-based combination regimens are recommended as 1L options for advanced/recurrent disease.7 31 32 33 34 The present study captures the EC treatment landscape prior to the shift in current guidelines. Nonetheless, in line with treatment guidelines at the time,5 7 32 chemotherapy remains a cornerstone of treatment for patients with EC. Particularly, the carboplatin/paclitaxel combination remains an established and preferred 1L for advanced/recurrent disease. However, subsequent retreatment with traditional cytotoxic chemotherapy remains challenging, considering factors such as the optimal duration of platinum-free intervals between treatment lines and the concept of “platinum sensitivity.”35 36 37 The latter is predominately based on small retrospective studies, along with expert opinion and healthcare practitioner experience.35 Although chemotherapy is administered to treat patients with advanced/recurrent EC, novel targeted therapies and immune-oncology approaches considering the patient's profile, molecular classification, and histology have demonstrated better effectiveness after the initial treatment.10 As our understanding of molecular classification evolves, precision medicine is reshaping the treatment approach for EC.10 35 Tailoring treatment approaches based on early molecular profiling of individual patients represents a promising approach to enhance antitumor effects.10 Notably, significant positive shifts in the management of EC in the front-line setting have been reported for patients with mismatch repair-proficient (MMRp)/microsatellite stable (MSS) and MMR-deficient (MMRd)/microsatellite instability-high (MSI-H) EC, who are amenable to immune-oncology treatment,10 35 as exemplified by novel therapies, namely pembrolizumab with or without lenvatinib approved for patients with MMRp/MMS tumor profiles38 39 and dostarlimab approved for patients with MMRd/MSS as well as MMRd/MSI-H tumor profiles.7 40 41 Promisingly, results from the phase III Study to Evaluate Dostarlimab plus Carboplatin-Paclitaxel versus Placebo plus Carboplatin-Paclitaxel in Participants with Recurrent or Primary Advanced Endometrial Cancer (RUBY trial)42 showed statistically significant and clinically meaningful OS benefits in patients with primary advanced/recurrent EC treated with dostarlimab in combination with carboplatin-paclitaxel compared to carboplatin-paclitaxel alone (hazard ratio  = 0.69; 95% CI: 0.54–0.89; p = 0.0020).

In line with the EC treatment landscape during the study period, in the current study, chemotherapy dominated the treatment choice in the 1L and 2L settings. Furthermore, the use of immunotherapy was low in 1L, with more than 10% of the patients receiving immunotherapy treatment, a rate that increased to more than 20% in 2L. The approval of dostarlimab in Brazil, in 2022 for 2L for patients with advanced/recurrent MMRd/MSI-H EC, and more recently in 2024 for 1L in combination with chemotherapy, is bringing patients in this region closer to accessing novel therapies. Consequently, we may observe a shift in treatment patterns.10 11 43

The ECHOS-B used data from the private healthcare system, which suggests that patients have access to optimal care; however, some potential limitations should be considered. The findings should be interpreted considering the specific population that the Orizon database represents. As patients at any stage of the disease could be included in our dataset, there are limitations to the interpretation and evaluation of the treatment patterns herein reported regarding disease severity. The subset of patients receiving PBT in 1L likely reflects those with advanced disease, either undergoing adjuvant or neoadjuvant therapy, and the study is limited in terms of distinguishing them. Due to this, the longer-than-expected rw PFS observed in the study may reflect this limitation, although, in our dataset, the number of patients treated with surgery and drugs was small (lower than 4%; data not shown). Treatments or hospitalizations that ultimately occur in the public healthcare system are not captured by the Orizon database; therefore, the results cannot be generalized to the population with lower socioeconomic status, or to the public healthcare system, to which all Brazilians have access.

Other limitations include those traditionally associated with retrospective analyses, such as problems with the quality of data recording in the local clinical practice and the availability of clinical information. In addition, analyses of data on administrative claims depend on correct coding for diagnoses, procedures, and drugs, such that any coding inaccuracies may lead to case misidentification.

The ECHOS-B provides valuable insight into real-world treatment patterns and outcomes for patients with EC in Brazil. Our findings demonstrate that PBT is frequently (∼ 70%) used in 1L, with high rates of progression and with most progression events occurring within 2 years. These findings enhance EC awareness and clarify current and emerging treatment options, particularly as clinicians gain experience with novel immunotherapies. Recent developments and approvals of novel immune-oncology therapies for advanced/recurrent EC will undoubtedly lead to improvements in patient outcomes both in Brazil and worldwide.