Adjusting Chemotherapy in Octogenarians With NSCLC

Corey J. Langer, MD

Corey J. Langer, MD, director of Thoracic Oncology at the University of Pennsylvania’s Abramson Cancer Center in Philadelphia, sees at least 1 new octogenarian patient with lung cancer each week. In the United States, the incidence of lung cancer has increased in those aged ≥75 years and will likely continue to rise; by 2020, it is estimated that 6.6 million people aged ≥85 years will be afflicted with the disease. ^1,2

New data presented at the 12th International Lung Cancer Congress demonstrate the need to adjust chemotherapies for the elderly population, in general, but even more data are needed to set chemotherapy standards for the growing group of octogenarians.³

“The elderly are a growing percentage of our patient population,” said Langer, one of the presenters at this year’s Congress. “Unfortunately, the elderly are horribly underrepresented in clinical trials.”

Langer stated that there is a lack of data for those aged >80 years, noting that the median age at diagnosis in advanced non—small cell lung cancer (NSCLC) is >70 years in the United States. However, the median age of most nonspecific trials is around 60 years. “Even in the elderly specific trials, the median age is 75 [years],” Langer said.

“The elderly are a growing percentage of our patient population. Unfortunately, the elderly are horribly underrepresented in clinical trials. ”

—Corey J. Langer, MD

According to Congress presenter Heather Wakelee, MD, assistant professor of Medicine at Stanford University’s Stanford Cancer Institute in California, well-selected elderly patients with metastatic disease do just as well as younger patients. “However, that is looking at 65 or 70 [years of age] as the cutoff point. When we [treat] octogenarians, there are very few patients in their 80s who are fit [enough] for chemotherapy,” she said. However, Wakelee indicated that patients who are fit can tolerate combination chemotherapy.

Heather Wakelee, MD

IFCT-0501

Wakelee and Langer discussed a recent multicenter phase III study published in Lancet.⁴ The IFCT-0501 trial (NCT00298415), led by Elisabeth Quoix, MD, of Strasbourg University Hospitals in Strasbourg, France, compared carboplatin and paclitaxel doublet chemotherapy with monotherapy in elderly patients with advanced NSCLC. Monotherapy is the current recommendation for patients aged ≥70 years.

Patients aged 70 to 89 years (median age, 77) with locally advanced or metastatic NSCLC and a World Health Organization (WHO) performance status of 0-2, were eligible for the trial. Patients received either 4 cycles of carboplatin plus paclitaxel or 5 cycles of vinorelbine or gemcitabine monotherapy (225 patients and 226 patients, respectively; N = 451). The study was an intention-to-treat analysis with a primary endpoint of overall survival (OS) and a median follow-up of 30.3 months. Median OS was 10.3 months for doublet chemotherapy and 6.2 months for monotherapy (hazard ratio, 0.64; 95% confidence interval [CI], 0.52-0.78; P <.0001). One-year survival was 44.5% (95% CI, 37.9-50.9) and 25.4% (95% CI, 19.9-31.3), respectively. Toxicities were more frequent in the doublet chemotherapy group (most frequent, decreased neutrophil count) than in the monotherapy group. Despite increased toxicities, the improvement in OS in the combination chemotherapy arm suggests that the current chemotherapy treatment regimen for these patients be reconsidered.⁴

“

When we [treat] octogenarians, there are very few patients in their 80s who are fit [enough] for chemotherapy. ”

—Heather Wakelee, MD

Caution and Considerations

Langer agrees that a number of factors, such as comorbidities, physiological reserve, marrow impairments, kidney function, and social resources must be considered when choosing chemotherapy treatments for this population, but said that the IFCT-0501 trial was one of the most strikingly positive solid tumor trials that he has seen in a number of years.

“Some argued that toxicities were excessive, but certainly when we look at this in the context of other trials in advanced disease in the elderly, I think the toxicity levels were acceptable,” he said.

“Those over 80 [years of age] are really a unique group,” said Langer. “The IFCT trial has helped us generate a much larger database in those over 80 [years], and certainly the survival benefit was seen for both age groups (ie, those between the ages of 70 and 80, and 80 and beyond). I would personally argue that we probably need to do additional trials in octogenarians. Octogenarians are a huge percentage of our practice.”

References

1. Sahyoun NR, Lentzner H, Hoyert D, Robinson KN. Centers for Disease Control and Prevention, National Center for Health Statistics. Trends in Causes of Death Among the Elderly, March 2001. Available at: www.cdc.gov/nchs/data/ahcd/agingtrends/01death.pdf. Accessed September 1, 2011.
2. Department of Health and Human Services. Administration on Aging. A Profile of Older Americans: 2010. Available at: www.aoa.gov/aoaroot/aging_statistics/Profile/2010/2.aspx. Accessed September 1, 2011.
3. OncLive. Meetings: 12th International Lung Cancer Congress. Langer, Scagliotti, and Wakelee presentations. August 11-14, 2011. Available at: www.onclive.com/conference-coverage/lung-cancercongress-2011. Accessed September 1, 2011.
4. Quoix E, Zalcman G, JP Oster, et al, on behalf of Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non—small cell lung cancer: IFCT-0501 randomised, phase 3 trial [published online ahead of print August 8, 2011]. Lancet. 2011. Available at: www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60780-0/fulltext#. Accessed September 1, 2011.