MS18.02 Treatment of Elderly Patients with SCLC

Abstract

Small cell lung cancer accounts for approximately 30,450 (13%) new cases of lung cancer each year in the United States. The worldwide incidence is unknown. SCLC frequently occurs in elderly patients as defined by >70 years of age. A recent analysis of the surveillance, epidemiology and end results (SEER) database showed the incidence of elderly patients diagnosed with SCLC increased from 23% in 1975 to 40% in 2010 with a quarter of patients age 80 or greater (1). Due to comorbidities associated with the aging process resulting in frailty and organ dysfunction, elderly patients (especially patients over the age of 80) may not be offered treatment and are underrepresented in clinical trials. This presentation will review the available retrospective and prospective data. Limited Stage SCLC (LS-SCLC) Concurrent chemoradiation is the standard of care for patients with limited stage disease. Three age-specific retrospective analyses of randomized, North American cooperative group studies evaluating cisplatin-based regimens did not demonstrate significant differences in overall survival or other efficacy endpoints by age (2). However, two of the studies reported significantly increased treatment related toxicity and mortality in the elderly population. To address the toxicity issue, phase II trials evaluated modified chemotherapy and radiotherapy regimens. These studies showed modified regimens were active and less toxic but no definitive trials have been performed. Alternatively, carboplatin is frequently substituted for the more toxic cisplatin in the concurrent regimen. Another approach is to omit the radiation and administer chemotherapy alone. However, a retrospective analysis of elderly LS-SCLC patients from the National Cancer Data Base from 2003 -2011 demonstrated the use of modern chemoradiation was superior to chemotherapy alone on univariate and multivariate analysis with a 3-year OS of 22% vs 6.3% respectively, P<.001. This effect was seen in patients 80+ years and in patients with comorbidities (3). A subset analysis also showed concurrent treatment significantly improved survival over sequential treatment. Similar findings were observed by the Dutch (4). Extensive Stage SCLC (ES-SCLC) Etoposide and a platinum agent (cisplatin or carboplatin) is the standard of care for upfront treatment of ES-SCLC. Despite the acceptance of etoposide plus carboplatin as a tolerable and equivalent regimen, elderly patients may not receive treatment. A review of the Alberta Cancer Registry revealed that 32% of patients age 75+ did not receive chemotherapy (5). Of the patients who received chemotherapy, 52% completed all cycles and 66% did not require a dose reduction. Patients who completed all cycles with a dose reduction had a decreased risk of death 1.02 (95% CI: 0.57-1.82) compared to a risk of death of 2.72 (95% CI: 1.52-4.87) for patients who did not complete therapy. Four phase II studies evaluating dose modifications of carboplatin and etoposide in the elderly found similar survival outcomes to standard doses (5). In a recent phase II study from China 34 elderly patients or patients with a PS of 2 who received carboplatin and etoposide had a median PFS of 5.8 months and an OS of 14 months (6). Toxicity was acceptable with Grade 3 or greater neutropenia and febrile neutropenia occurring in 40% and 7% of patients, respectively. Prophylactic Cranial Irradiation The role for prophylactic cranial irradiation (PCI) in the elderly population is controversial. Retrospective population based and trial specific analyses have shown that PCI improves survival compared to no PCI but concern over increased neurocognitive dysfunction has resulted in limited uptake of PCI (7-9). Indeed, a comparison of tested and self-reported cognition in two RTOG trials evaluating PCI in patients with LS-SCLC demonstrated higher rates of cognitive decline with advanced age (10). Modern radiation techniques, hippocampal sparing and memantine may reduce the rate of cognitive decline. Recent data also suggests that MRI surveillance may be an option for patients with ES-SCLC (11). Geriatric Assessment Tools Geriatric oncology is addressing the optimal approach to the care of these patients through the development of geriatric assessment tools to better define risks and benefits. Investigators are encouraged to incorporate these tools into their clinical trials. Treating physicians should also consider using validated geriatric assessment tools in their routine practice such as the new ASCO 2018 guideline (12). Overall, elderly patients should be offered standard treatment but they may require dose modifications. Participation in clinical trials and trials that address the unique needs of the elderly are strongly encouraged. Abdel-Rahman O. Changing epidemiology of elderly small cell lung cancer patients over the last 40 years; a SEER database analysis. Clin Respir J. 12:1093-9, 2018. Palis AG, et al. Treatment of small-cell lung cancer in elderly patients. Cancer. 116:1192-200, 2010. Corso CD, et al. Role of Chemoradiotherapy in Elderly Patients With Limited-Stage Small-Cell Lung Cancer. J Clin Oncol. 33:4240-6, 2015. Janssen-Heijnen ML, et al. Tolerance and benefits of treatment for elderly patients with limited small-cell lung cancer. J Geriatr Oncol. 5:71-7, 2014. Fisher S, et al. 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