GOG 273 is the first study directed toward elderly women with ovarian carcinoma receiving first-line chemotherapy to assess tolerance and predict the ability to complete therapy.
—Amina Ahmed, MD
Geriatrics for the Oncologist is guest edited by Stuart Lichtman, MD, and developed in collaboration with the International Society of Geriatric Oncology (SIOG). Visit SIOG.org for more on geriatric oncology.
The elderly population in the United States is growing, and by the year 2050, persons older than 65 years of age will comprise 20% of the population. Not only will there be an increase in the number of persons aged 65 years and older, the life expectancy of those older than 65 years of age has increased; so the number of those older than 85 years of age is expected to double to 8.9 million by 2050.
As the population ages, diseases that affect the elderly will become more prevalent. Increasing age is associated with increasing rates of cancer, with persons older than 65 years of age accounting for 60% of newly diagnosed malignancies and 70% of all cancer deaths.1
Rates of gynecologic cancers increase with age; the median age at diagnosis for ovarian cancer is 63 years, with 40.8% of diagnosed cases in those 65 years and older. Of the cases diagnosed in the elderly, half were diagnosed after age 75 years.2 A total of 40% of patients with endometrial carcinoma are diagnosed after age 65 years, and 43% of patients older than age 75 years will have an advanced stage at presentation.3
Underrepresented in Clinical Trials
Despite the high cancer incidence in the elderly population, older patients are still underrepresented in clinical trials. There is a general paucity of data on treatment efficacy and toxicity in elderly women with gynecologic malignancies. The lack of information from elderly patients may contribute to the increased risk of toxicity from treatment and poor outcomes observed in this group.
Many unanswered questions remain: Under what situations should a full dose be maintained? What can be done to ameliorate toxicities? When are we likely to have a negative functional outcome, such as causing a formerly independent patient to have to move to a nursing home?
In 1995, the Cancer and Leukemia Group B (CALGB) organized a Cancer in the Elderly Committee, which was led by Hyman Muss, MD, and Harvey Cohen, MD, with vice chairs Arti Hurria, MD, and Aminah Jatoi, MD. The newly formed Alliance for Clinical Trials in Oncology (CALGB, the North Central Cancer Treatment Group, and the American College of Surgeons Oncology Group) maintained this strengthened committee. The Gynecologic Oncology Group (GOG) formed an Elderly Working Group in 2010, led by Gini Fleming, MD, to try to improve outcomes for older patients. The activities of the GOG, now the NRG Elderly Working Group, are summarized here.
NRG Elderly Working Group Studies
Elderly patients with ovarian carcinoma may have significant comorbidities, which can affect treatment choices or produce worsened toxicities and impact survivorship and quality of life. They are also more prone to certain toxicities, particularly neuropathy.
GOG 273 is the first study directed toward elderly women with ovarian carcinoma receiving first-line chemotherapy to assess tolerance and predict the ability to complete therapy. GOG 273 was opened in August 2011.
Vivian von Gruenigen, MD, the study chair, presented a preliminary report of GOG 273 at the 2014 Society of Gynecologic Oncology Annual Meeting. Physician-selected treatment arm 1 consisted of carboplatin, paclitaxel, and granulocyte colony-stimulating factor every 3 weeks and arm 2 consisted of carboplatin only every 3 weeks. Patients treated on arm 1 were younger, more fit, and had higher chemotherapy completion rates and required fewer dose reductions or delays than patients treated on arm 2.
Multivariate analysis revealed that assignment to arm 2, neoadjuvant chemotherapy, and limited social activities (but not instrumental activities of daily living) were associated with an inability to complete four cycles of chemotherapy. Impressively, quality of life improved in patients on both arms, likely reflecting the efficacy of chemotherapy in this disease.
A third arm was added to GOG 273 in 2013, as there was a desire to assess tolerance of the popular regimen of dose-dense chemotherapy with weekly paclitaxel and every 3-week carboplatin. Analysis of data from this third arm is underway. In addition, a parallel study is being conducted by NRG Oncology Japan, which is an exciting opportunity to see whether cross-cultural use of tools such as a Geriatric Assessment Score has similar predictive power. As accrual goals have been met, GOG 273 is now closed.
More recently, NRG CC-002, the second trial through the NRG Elderly Working Group for which I served as study chair, was opened in February 2015. This prospective study is evaluating whether a preoperative Geriatric Assessment Score will be associated with major postoperative complications in elderly women with suspected ovarian, fallopian tube, primary peritoneal, or advanced-stage papillary serous uterine carcinoma undergoing open cytoreductive surgery.
The study is accruing well, and as of June 2015, approximately 69 patients have been enrolled. An interim analysis is underway to see how many patients are receiving primary surgical cytoreduction vs interval cytoreduction vs no surgery. In the future, the hope is to incorporate a standardized Geriatric Assessment Score into all trials, allowing a platform for comparison of outcomes for older patients. This way it will be possible to determine whether a study allowed only the healthiest elders or also included a more vulnerable population.
Other Concepts and Expanded Disease Sites
Numerous other concepts are currently being developed by the NRG Elderly Working Group. A few of them are listed here:
The NRG Elderly Working Group is excited to expand its involvement to other disease sites. A retrospective review of outcomes in legacy Radiation Therapy Oncology Group (RTOG) head and neck cancer trials was presented at the 2015 ASCO Annual Meeting by Julie Ann Kish, MD, FACP.4 It demonstrated that patients aged 70 years and older were underrepresented in RTOG trials evaluating treatment for locally advanced head and neck cancer relative to the overall population and had worse survival than patients younger than age 70 years. A trial that would randomize patients aged 70 years or older with head and neck cancer to receive either cetuximab (Erbitux) or anti–PD-1 (programmed cell death protein 1) therapy with radiation is being proposed.
Work continues across tumor types to refine our ability to predict which older patients will not tolerate standard therapy well, to find regimens that improve cancer outcomes in older patients, and to decrease toxicity in older patients. ■
Disclosure: Dr. Ahmed reported no potential conflicts of interest.
1. Berger NA, Savvides P, Koroukian SM, et al: Cancer in the elderly. Trans Am Clin Climatol Assoc 117:147-156, 2006.
2. Howlader N, Noone AM, Krapcho M, et al (eds): SEER Cancer Statistics Review, 1975-2008, National Cancer Institute. Bethesda, MD. Available at http://seer.cancer.gov/csr/1975_2008/, based on November 2010 SEER data submission, posted to the SEER web site, 2011. Accessed July 2, 2015.
3. Lee NK, Fleming GF: Treatment of advanced stage and recurrent endometrial cancer in elderly women, in Lichtman SM, Audisio RA (eds): Management of Gynecological Cancers in Older Women, pp 257-275. London, Springer-Verlag London, 2013.
4. Kish JA, Zhang Q, Langer CJ, et al: The effect of age on outcome in prospective, phase III NRG Oncology/RTOG trials of radiotherapy ± chemotherapy in locally advanced head and neck cancer. 2015 ASCO Annual Meeting. Abstract 6003.
Dr. Ahmed is a gynecologic oncologist, Advocate Health Care, Section of Gynecologic Oncology, Lutheran General Hospital, Park Ridge, Illinois.
Dr. Lichtman is an Attending Physician at Memorial Sloan Kettering Cancer Center, Commack, New York, and Professor of Medicine, Weill Cornell Medical College, New York. He is also President Elect of the International Society of Geriatric Oncology (www.siog.org).