Clinical outcomes of hematopoietic growth factors and the value of neoadjuvant chemotherapy in a large cohort of elderly patients with advanced ovarian cancer
Abstract
Erythropoietin stimulating agent (ESA) and granulocyte colony stimulating factor (CSF) are hematopoietic growth factors used to treat chemotherapy related bone-marrow suppression in cancer patients. While successful use has been demonstrated in controlled experimental trials of patients with advanced stage ovarian cancer, little is known about the usefulness and safety of these agents in routine clinical practice. Notably, there has also been a slight deviance in the standard-line of treatment for advanced ovarian cancer in recent years; wherein the tumor lump is treated by administering first-line neoadjuvant chemotherapy compared to primary debulking surgery. While, an on-going deliberation on the usefulness of this practice continues till date, none have studied the monetary feasibility of the procedure. The objectives of this dissertation were to conduct a population-based analysis to evaluate the effectiveness and adverse-events associated with growth factor use in a cohort of elderly women with advanced stage ovarian cancer. In addition, the project also estimated the cost-effectiveness of administering neoadjuvant chemotherapy (NAC) compared to primary debulking surgery (PDS), using data from the linked Surveillance Epidemiology and End Results (SEER)-Medicare database. The first study explored the effectiveness of ESA (i.e., epoetin-alfa and darbepoetin-alfa) and CSF (i.e., filgrastim and pegfilgrastim) in reducing blood transfusion needs and neutropenia incidence, respectively, and also assessed the effect of these agents on overall survival. Depending on the number of claims administered, use of an ESA lowered the need for blood transfusion by 48-78%, and use of a CSF reduced the incidence of neutropenia by 68-98%. An overall survival advantage was observed among patients who received CSF only; while, those who received ESA only experienced a higher mortality after 24 months. The second study assessed the risk of thromboembolic and pulmonary toxicities in patients who received ESA and/or CSF. Of 8,188 patients included, 24% received ESA only, 13% CSF received only and 30% received ESA+CSF. The cumulative-incidence of thromboembolic and pulmonary toxicities at two and six-months of follow-up was highest among patients who received ESA+CSF, with deep vein thrombosis, stroke, myocardial infarction, dyspnea/ respiratory abnormalities, anaphylaxis/ allergic reactions and other/ unclassified events occurring more commonly. The multivariate Cox regression model showed that patients who received ESA+CSF were at a 1.2 times higher risk of a thromboembolic event; which may be up to 5-folds higher in patients who were >85 years. However, there was no significant difference in the risk of pulmonary toxicities depending on growth factor use. The third study estimated the cost-effectiveness of NAC compared to PDS from a payer perspective. Of 4,843 cases that were included, 12% received NAC before surgery and 88% received PDS. Patients who received NAC incurred an average lifetime cost that was $17,417 more than those who received PDS. At only 0.1 incremental life-year gained, the ICER estimate was $174,173. On stratifying the analysis by risk groups (categorized based on tumor stage, patient age and comorbidity score), the incremental costs and gain in life-years in the high risk subgroup treated with NAC was $34,390 and 0.8 life-years, resulting in an ICER of $42,987. However, NAC use was dominated by PDS in the non-high risk subgroup (i.e., more costly, less effective). In conclusion, the population-based effectiveness of hematopoietic growth factors in elderly patients with advanced ovarian cancer is consistent with evidence from clinical trials and currently existing clinical guidelines. Since patients who receive both ESA and CSF may be at an increased risk of thromboembolic toxicities, the risk-benefit ratio must be carefully evaluated prior to administering these agents. This is particularly important for patients aged 85 years and over. Finally, the use of NAC prior to surgery may be a cost-effective treatment approach for patients in the high risk subgroup, at the ‘traditional’ levels of willingness to pay; though, similar outcomes are not supported for the overall ovarian cancer sample or patients in the non-high risk subgroup.
Subject Area
Medicine|Public health|Epidemiology
Recommended Citation
Poonawalla, Insiya B, "Clinical outcomes of hematopoietic growth factors and the value of neoadjuvant chemotherapy in a large cohort of elderly patients with advanced ovarian cancer" (2015). Texas Medical Center Dissertations (via ProQuest). AAI3720093.
https://digitalcommons.library.tmc.edu/dissertations/AAI3720093