Are Elderly Patients With Advanced Non–Small Cell Lung Cancer Being Treated With a Platinum Doublet?

Are Elderly Patients With Advanced Non–Small Cell Lung Cancer Being Treated With a Platinum Doublet?

Dr. Elisabeth Quoix
During the 2010 ASCO Annual Meeting Plenary Session, Elisabeth Quoix, MD, of the University Hospital of Strasbourg, France, provided compelling data from the IFCT 0501 study showing that, compared with single-agent therapy with vinorelbine or gemcitabine, elderly patients with advanced non–small cell lung cancer (NSCLC) treated with the doublet of monthly carboplatin and weekly paclitaxel had significantly longer median survival times (10.3 months vs. 6.2 months) and 1-year overall survival rates (OS; 45.1% vs. 26.9%; p = 0.0004).1,2

The presentation was notable because elderly patients with advanced cancers, particularly advanced NSCLC, are generally undertreated. Why does this disparity exist, and have we made progress in the past 5 years?

Why Elderly Patients With NSCLC Are Undertreated

Prior to the Plenary Session data presented by Dr. Quoix, which were subsequently published in The Lancet,2 data-driven clinicians were hard pressed to treat elderly patients with therapy proven for younger patients. As Dr. Quoix noted in a review article, the Surveillance, Epidemiology, and End Results database and registries indicate that only one in four older patients receive appropriate first-line treatment for NSCLC.3

Dr. David S. Ettinger
David S. Ettinger, MD, FACP, FCCP, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, noted that with an increase in life expectancy, the average age at diagnosis for advanced NSCLC is 70 years, and elderly patients are underrepresented in clinical trials, where the average age of patients enrolled is 63 to 64 years.

“Indeed, it is generally acknowledged that clinicians are reluctant to treat elderly patients due to accompanying comorbidities, poor performance status, and frailty,” Dr. Ettinger said.

In the IFCT 0501 study, 451 elderly patients (aged ≥ 70 years) with advanced NSCLC received either a platinum doublet with carboplatin given at an area under the curve of six on day 1 plus paclitaxel 90 mg/m2 on days 1, 8, and 15 every 28 days or gemcitabine 1,150 mg/m2 or vinorelbine 25 mg/m2 on days 1 and 8 every 21 days.1,2

“This study was the first to prospectively and conclusively prove that elderly patients with NSCLC benefit from a platinum doublet, and it provided oncologists the comfort of using this regimen in clinical practice,” Apar K. Ganti, MD, MS, told the ASCO Daily News. “Prior to Dr. Quoix’s study, we only had retrospective and subgroup analyses using small patient numbers.”

Dr. Apar K. Ganti
Dr. Ganti treats elderly patients with NSCLC at the U.S. Department of Veterans Affairs Nebraska-Western Iowa Health Care System.

Before 2011, treatment of patients with a reasonable performance status had been guided by data from the ELVIS and MILES studies, explained Mark Socinski, MD, of the University of Pittsburgh Medical Center. In the ELVIS study, single-agent vinorelbine provided a response rate of 20% versus best supportive care, with a 1-year survival of 32% versus 14%4; in the MILES study, single-agent vinorelbine or gemcitabine provided no significant difference in median survival (36 weeks and 28 weeks, respectively) or response rates (18% and 16%, respectively) compared with the combination of vinorelbine and gemcitabine (median survival, 30 weeks; response rate, 21%).5

Dr. Mark Socinski
“Dr. Quoix’s study has made a difference in the treatment of elderly patients,” Dr. Socinski said. “It has reinforced the concept that aggressive treatment with two drugs can provide significant survival benefits for patients.”

Current Treatment Landscape for Elderly Patients With NSCLC

But how pervasive is this practice of treating elderly patients with a doublet? “Contrary to common practice of treating elderly patients with single-agent chemotherapy, patients with good performance status and few comorbidities should currently be offered a standard doublet, usually with carboplatin,” Dr. Ettinger said.

An analysis of three clinical trials in the first-line treatment of elderly patients with NSCLC with platinum doublet therapy showed that carboplatin-based doublet therapy (carboplatin/paclitaxel, carboplatin/gemcitabine, and cisplatin/docetaxel) was useful and tolerable in older patients. However, the carboplatin/paclitaxel doublet—the Quoix regimen—was the only regimen associated with better survival.6 The cisplatin/docetaxel doublet failed to provide a survival benefit in patients older than age 70.6

“The Quoix regimen, pemetrexed/carboplatin, and nabpaclitaxel/carboplatin are among some of the preferred regimens based on clinical trial data,” Dr. Ettinger said. “They all offer better clinical benefits (e.g., higher progression-free survival and higher overall response rates) compared with single-agent chemotherapy.” Pemetrexed/carboplatin is used exclusively for patients with nonsquamous NSCLC, Drs. Ettinger and Ganti noted.7

For elderly patients who either do not want or cannot tolerate chemotherapy, targeted therapy with erlotinib or crizotinib is provided in the context of appropriate mutations—EGFR mutations for erlotinib and ALK translocations for crizotinib.3,8,9 In addition, there is general consensus that bevacizumab may not benefit elderly patients with NSCLC.3,8,9

Platinum Doublet Is the New Standard of Care for Elderly Patients With NSCLC

Dr. Quoix’s Plenary presentation was instrumental in platinum doublet becoming the standard of care for elderly patients with NSCLC. The National Comprehensive Cancer Network Older Adult Oncology guidelines indicate that, if an older patient is deemed to be fit, it is reasonable to use treatment options recommended for younger individuals.10 However, comorbidities and a geriatric assessment must be undertaken.

Although comorbidities and geriatric assessment can be determined with validated instruments, most physicians do not use them because it takes time, Dr. Ettinger said. Dr. Ganti agreed. In his own practice, he determines the Eastern Cooperative Group performance status score and evaluates patient’s comorbidities, general functional abilities, social support, and independent function in a more informal manner.

In addition, Dr. Ganti indicated that the carboplatin/paclitaxel schedule used by Dr. Quoix and her group is cumbersome to deliver because it requires that patients come weekly for chemotherapy. In several practices, although the platinum doublet is indeed used, both drugs are administered at the convenient schedule of once every 3 to 4 weeks for four to six cycles, he explained. Paclitaxel is given at a dose of 200 mg/m2, and the 3- to 4-week schedule is dependent on hematologic recovery.

“The impact of the Quoix paper may not be immediately apparent if one is looking for changes in survival statistics based on national databases,” Dr. Socinski said. Although the Quoix data are compelling and have made an impact at academic centers, we do not know whether the practice of treating elderly patients with NSCLC by community oncologists is pervasive, he noted.

“On a national basis, there is a sense of nihilism regarding the treatment of elderly patients in the disciplines of primary care, as well as pulmonary medicine,” Dr. Socinski continued. “Many elderly patients may not be referred for oncologic evaluation based on the incorrect assumption that chemotherapy provides little benefit in this situation.”

Dr. Ganti stressed that, although older patients receiving the platinum doublet are still in the minority, the change is occurring even at community centers. However, Drs. Socinski and Ganti are both of the opinion that it will be several years before we see changes in the survival statistics for elderly patients with NSCLC. 

Because clinicians are reluctant to provide elderly patients with the clinical options available to younger patients, it is important to undertake clinical trials independently in older patients to show that they stand to benefit from the same standard of care applied to younger patients, Dr. Ganti said. It is a prospective study in elderly patients with NSCLC that has changed the standard of care, he noted. 

It is difficult to assess the global uptake of the platinum doublet in elderly patients with NSCLC. Dr. Quoix indicated that the platinum doublet is the current standard of care in France in all elderly patients with a performance status of 0 and 1. Given the success of study IFCT 0501, Dr. Quoix has now undertaken a follow-up study (NCT01850303) investigating the efficacy of maintenance therapy with gemcitabine (for squamous NSCLC) or pemetrexed (for nonsquamous NSCLC) versus placebo in elderly patients with NSCLC who respond to four cycles of the platinum doublet.  

– Alexander Castellino, PhD