Abstract: This article aims to quantify the use of health services during the watchful waiting period after second-line platinum-based therapy among patients with ovarian cancer. Women newly diagnosed with ovarian, fallopian tube, or primary peritoneal cancer between January 1, 2010, and September 30, 2015, and subsequently treated with 2 lines of platinum-containing chemotherapy were selected from the MarketScan® claims data. Inpatient admissions, emergency room (ER) visits, and their associated diagnoses and costs were analyzed during the watchful waiting period. A total of 1176 patients were included. The median duration of watchful waiting was approximately 5.5 months. During the watchful waiting period, 41.8% had either an inpatient admission or ER visit. Approximately 30% of patients were hospitalized for a total of 585 admissions (1.7 admissions per hospitalized patient), with an average (standard deviation [SD]) cost per hospitalization of $27,802 ($36,032). Overall, 320 patients had 679 ER visits (2.1 per patient) with an average (SD) cost per patient with ER visits of $1115 ($1974). Findings suggest a substantial ongoing disease burden with frequent hospitalization and ER visits during the watchful waiting period.
It is estimated that there will be more than 22,000 new ovarian cancer cases and approximately 14,000 deaths due to ovarian cancer in the United States in 2017.1 Most diagnoses (88%) occur at ages 45 and older and at a median age of 63.1 Prognosis is improved for patients diagnosed at earlier stages: 5-year survival is 92.5% for women diagnosed with localized disease, 73.0% for those with regional lymph node involvement, and 28.9% for those with distant metastases.1,2 Unfortunately, most women (80%) are diagnosed with regional or distant metastases.1
National Comprehensive Cancer Network (NCCN) treatment guidelines recommend primary surgical cytoreduction or neoadjuvant chemotherapy as the primary treatment for most cases of ovarian cancer, followed by a chemotherapy regimen.3 The cornerstone of drug treatment in the first-line advanced disease setting is platinum therapy (cisplatin or carboplatin) plus a taxane (paclitaxel or docetaxel).4,5 Following first-line treatment, 85% of patients will experience disease recurrence, at which point the cancer is considered incurable.4,5 Recurrent disease is usually treated again with platinum-based chemotherapy as long as progression occurred more than 6 months after the last dose of chemotherapy (which suggests platinum sensitivity).6-8 Duration of progression-free survival (PFS) decreases with each subsequent line of chemotherapy.9,10 Risk for cumulative toxicities also increases with each line of treatment.9,10 After response to platinum-based therapy, for patients responding to platinum treatment NCCN guidelines recommend disease monitoring, consisting of clinic visits, pelvic examinations, cancer antigen 125 monitoring, imaging, and genetic risk evaluation. Patients with recurrent disease may also be treated with poly (ADP-ribose) polymerase (PARP) inhibitor or bevacizumab maintenance therapy.3 Given the equal weighing of observation vs proven maintenance treatments by NCCN guidelines, many patients enter an observational period (“watchful waiting”) and do not receive maintenance treatment.
There is little research on the burden of illness during watchful waiting periods. Studies usually focus on a particular period of time after initial diagnosis or surgery11,12 or phases of care that include some active treatment.13 Studies conducted during watchful waiting have focused on surveillance costs14 or the cost-effectiveness of maintenance therapies.15,16 The objective of this study was to investigate the frequency and timing of hospitalizations and emergency room (ER) visits that occur during the watchful waiting period after second-line platinum treatment and quantify the associated direct health care costs.
This retrospective cohort study conducted in the United States used administrative health care claims data from the 2009-2015 MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Databases (IBM Watson Health). These databases contain the complete longitudinal records of inpatient and outpatient services and prescription drug claims for an annual average of 37 million commercially insured and 3 million Medicare-eligible individuals in each of the study years, covered under a variety of commercial health plans, including dates of service, places of service, and all payments. All database records are de-identified and fully compliant with US patient confidentiality requirements set forth in Sections 164.514 (a)-(b)1ii of the Health Insurance Portability and Accountability Act (HIPAA) regarding the determination and documentation of statistically de-identified data. Because this study used only de-identified patient records and did not involve the collection, use, or transmittal of individually identifiable data, institutional review board approval to conduct this study was not necessary.
Patients were selected who had 1 or more inpatient claims or 2 or more outpatient claims ≥30 days apart with a diagnosis of ovarian, fallopian tube, or primary peritoneal cancer, identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 183.0: Malignant neoplasm of ovary; 183.2: Malignant neoplasm of fallopian tube; 158.x: Malignant neoplasm of retroperitoneum or peritoneum, between January 1, 2010, and September 30, 2015. The index date was the date of the earliest qualifying claim for ovarian cancer. Patients were required to be at least 18 years old on their index date and continuously enrolled in health insurance with both medical and pharmacy benefits for ≥12 months before and ≥1 month after their index date with no medical or pharmacy claims indicative of ovarian cancer within 12 months before the index date to ensure that they were newly diagnosed. Patients were followed up starting with the index date until the earliest of the end of continuous insurance enrollment, inpatient death, or the end of the study period (September 30, 2015). Patients were further required to have had 2 lines of platinum-based chemotherapy (ie, platinum-based chemotherapy during first-line and second-line) with no maintenance therapy during second-line treatment
(Figure 1; see Table 1 for a list of therapies).
Age, geographic region, and primary payer type were assessed at the index date. The presence of comorbid conditions was assessed using diagnoses recorded during the baseline period of 12 months before the index date. The National Cancer Institute (NCI) modified Deyo-Charlson comorbidity index17 was computed using diagnoses during the baseline period. The presence of metastatic disease at index was assessed using diagnoses of secondary neoplasms recorded during the baseline period, specifically ICD-9-CM 197.xx: Secondary malignant neoplasms of respiratory and digestive system and 198.xx: Secondary malignant neoplasms of other specified sites (excludes lymph nodes).