Optimizing Therapeutic Approaches in Older Women with Ovarian Cancer

Epithelial ovarian cancer typically occurs in the elderly, with a median age at diagnosis of 63 years.1 Because elderly patients are underrepresented in clinical studies, prospective data offering clinical guidance for these patients are scarce.

Saturday’s Education Session, “Managing Ovarian Cancer in the Older Woman: How to Best Select and Sequence Surgery and Chemotherapy for Optimal Outcome” (to be held 8:00 AM-9:15 AM, in room E354b), will address the challenges clinicians face in treating older women with ovarian cancer. Based on retrospective data and those from emerging prospective studies in the elderly, the message is clear: It is possible to optimize therapeutic approaches without negatively affecting quality of life, and geriatric assessment tools will help in this process.

Chair Linda R. Duska, MD, of the University of Virginia Health System, said she will discuss how in order “to improve the outcomes of older women with ovarian cancer, we need to develop better decision aids to [identify] those patients who will and will not tolerate standard cytoreductive surgery and chemotherapy.”

Surgical Approaches

Retrospective data for patients with advanced disease indicate that surgery increases survival for patients with advanced-stage disease if they undergo an “optimal” cytoreductive surgery (CRS). However, the morbidity associated with optimal primary CRS may not make it an appropriate option for all older women. Some older women may benefit from interval CRS (iCRS), a clinical situation in which an optimal CRS will be likely be less morbid, because of the delivery of neoadjuvant chemotherapy.

Dr. Linda R. Duska

Dr. Duska will highlight factors that are associated with poor surgical outcomes in the elderly: age older than 75 years, poor performance status (PS), low serum albumin, presence of ascites, and high preoperative CA-125.

However, with age being a consideration for surgery, Dr. Duska will highlight analyses from the American Cancer Society indicating that worse prognosis may be associated with a less aggressive surgical approach taken in older women. Other factors that emerge that may account for the poor prognosis include older women seeing general surgeons and a suboptimal CRS performed.

Dr. Duska will provide insights from more recent single-institution studies that show that older women can tolerate aggressive surgery, and, in these instances, overall survival rates compare favorably with their younger counterparts. However, there are exceptions, especially in elderly patients with a substantial number of comorbidities. Dr. Duska will share Surveillance, Epidemiology, and End Results Program (SEER) data showing that older women are not likely to receive adjuvant chemotherapy or may receive delayed treatment if they present with comorbidities, have mucinous tumors, and have stage IV disease.2

Finally, although older women may successfully undergo optimal primary CRS, they are then less likely to receive a full course of chemotherapy, or perhaps may not receive chemotherapy at all, as a result of the morbidity of an aggressive upfront surgical approach. Because the successful treatment of advanced disease requires both surgery and chemotherapy, the failure to deliver a complete course of chemotherapy in a timely fashion may negate the advantage of an optimal CRS.

Indeed, identifying older women who are unlikely to benefit from aggressive primary CRS remains a challenge. Developing an algorithm that takes into account all risk factors would be helpful; ultimately, the best treatment options should be individualized and not based solely on chronologic age. Dr. Duska will discuss how certain elderly women should be offered neoadjuvant chemo-therapy and iCRS, or in some cases, chemotherapy alone. It is important to prospectively determine elderly patients who are candidates for primary CRS. There is an urgent need for a validated pre-assessment tool for use in this specific population.

Chemotherapy Choices

Data from the SEER Medicare database indicate that the odds of chemotherapy being offered to elderly patients decreases with age. For example, more than 50% of women older than age 80 who are diagnosed with ovarian cancer are never offered treatment. Kathleen N. Moore, MD, of the University of Oklahoma Health Sciences Center, will dispel two myths that are associated with not offering chemotherapy to the elderly: (1) ovarian cancer in the elderly may not be chemosensitive, and (2) the elderly patient may not be able to tolerate modified platinum-based chemotherapy.

Dr. Kathleen N. Moore

French groups, such as GINECO, and Italian groups, such as MITO, have championed clinical trials in elderly patients with ovarian cancer. Only recently, the Gynecologic Oncology Group (GOG) in the United States has completed the landmark GOG 273 study, which offers guidelines on the best therapeutic options for these patients. Dr. Moore’s discussion will focus on three points: (1) dose modifications in the elderly, (2) variations in treatment schedules, and (3) timing of chemotherapy.

She will draw upon the Elderly Women with Ovarian Cancer (EWOC) studies from the GINECO group to show that elderly patients can complete chemotherapy at modified doses. In EWOC-1, for which the median age was 76 years, 72% of patients completed the six cycles of carboplatin (AUC 5) and cyclophosphamide (600 mg/m2) chemotherapy with minimal toxicities. Indeed, toxicities could be predicted from three factors in the geriatric assessment: depression, dependence, and performance status.3 EWOC-2 showed that 68% of the patients were able to tolerate carboplatin (AUC 5) and paclitaxel (175 mg/m2) once every 3 weeks.4

The GOG 273 study enrolled women with ovarian cancer older than age 70. The chemotherapy choice was physician and patient based and was either single-agent carboplatin (AUC 5) or a doublet of paclitaxel (135 mg/m2) and carboplatin (AUC 5) given every 3 weeks. The primary endpoint of the study was the Lawton Instrumental Activities of Daily Living score to predict completion of four cycles of chemotherapy.

The study offered some insight into how to treat elderly patients with cancer. Dr. Moore will share data from the study, which showed that women opting for single-agent carboplatin compared with women opting for the doublet of paclitaxel and carboplatin were older (mean age: 83 years vs. 72 years, respectively), had a lower PS (PS 2-3: 37% vs. 11%, respectively), were more likely to receive neoadjuvant chemotherapy (58% vs. 49%, respectively), and were less likely to complete their prescribed therapy without a dose reduction (54% vs. 82%, respectively).

A striking observation was that 92% of patients receiving single-agent carboplatin completed the four courses of therapy, compared with 75% of those in the paclitaxel–carboplatin arm. GOG 273 did not meet its primary endpoint. Dr. Moore will indicate that although treatment may not improve the typical clinical parameters, the improvement in quality-of-life scores underscores the need for treating these women.

With respect to variations in scheduling, Dr. Moore will provide insights from the MITO-5 and MITO-7 studies. MITO-5 evaluated the tolerability of weekly carboplatin (AUC 2) and paclitaxel (60 mg/m2) given on days 1, 8, and 15, every 4 weeks for six cycles in women over age 70.5 MITO-7 compared the weekly regimen from MITO-5 to a standard regimen of carboplatin (AUC 6) and paclitaxel (175 mg/m2) every 3 weeks.6 The weekly regimen was associated with lower toxicity and higher quality-of-life scores. Median progression-free survival was similar across the two arms, making this weekly regimen an
attractive one for elderly patients.

Geriatric Assessment Tools Predict Outcomes

William P. Tew

In the final presentation, William P. Tew, MD, of the Memorial Sloan Kettering Cancer Center, will highlight the significance of using geriatric assessment tools to better define patients with a high risk of developing chemotherapy-related toxicity.

Dr. Tew will discuss a simple geriatric assessment tool that he developed with his colleagues at the Cancer and Aging Research Group (CARG), which can be used in geriatric patients before starting chemotherapy.7

This 11-point geriatric assessment tool looks at factors that can predict grade 3-5 toxicities in older patients. The variables of the tool include age older than 73 years, receiving standard-dose or multiple-agent chemotherapy, anemia, low creatinine clearance, impaired hearing, inability to walk a block, decreased social activity, assistance in taking medications, and having had a fall in the last 6 months. The tool was far superior to a physician-rated performance status alone in predicting toxicity.

In GOG 273, the geriatric assessment tool was applied before and after treatment. Dr. Tew will discuss how several geriatric variables improved in patients receiving chemotherapy, including social support and functional dependence.

Dr. Tew will also review the current preoperative assessments available to surgeons and how to apply them to older patients who are considered vulnerable. He will highlight data from the PACE study, which looked at patients with cancer older than age 70 undergoing complex surgery.

Three variables were the best predictors for poor post-surgical outcomes: functional dependence, fatigue, and poor performance status. However, the PACE study did not include any women undergoing CRS for ovarian cancer.

Dr. Tew will share retrospective data from older women diagnosed with ovarian cancer who underwent surgery at Memorial Sloan Kettering Cancer Center. Several factors, including poor functional status, poor cognition, and polypharmacy were associated with decreased survival.

Finally, Dr. Tew will highlight a simple preoperative assessment tool being developed in a prospective study by NRG Oncology for women with newly-diagnosed ovarian cancer. Similar to the CARG geriatric assessment tool and the PACE study, this tool will determine if it is possible to identify patients early who may be at risk for complications from surgery and who are better suited for neoadjuvant chemotherapy.

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