Doublet Chemo Proves Superior to Single-agent Therapy in Older Patients with Advanced Non-small-cell Lung Cancer

ABSTRACT: Data from French trial should inform treatment decisions in the majority of lung cancer patients aged 70 and up.

"This is the first study entirely devoted to elderly patients showing the superiority of a carboplatin doublet over single-agent therapy." - ELISABETH QUOIX, MD

Single-agent therapy is the standard of care for older patients (70 and above) because of toxicity concerns, while younger patients generally receive more potent combination therapy. Data from the French Intergroup of Thoracic Oncology have indicated that older patients may also benefit from combination therapy, and the results could herald a new treatment paradigm for a graying patient population.

Did You Know? IFTC-0501 enrollment IFTC-0501 had initially planned to include 520 patients, but enrollment was stopped early because an interim analysis showed a significant improvement in median survival time for the patients in the combination therapy arm.

"This is the first study entirely devoted to elderly patients showing the superiority of a carboplatin doublet over single-agent therapy in advanced non-small-cell lung cancer," said lead investigator Elisabeth Quoix, MD, a professor of medicine at University Hospital in Strasbourg, France.

TABLE 1 IFCT-0501 trial treatment arms

The phase III study (IFCT-0501) evaluated the efficacy and safety of weekly paclitaxel combined with monthly carboplatin vs single-agent therapy in patients aged 70 to 89 years old with advanced lung cancer. Patients (n = 451) were randomized into two treatment arms (see Table 1). Patient characteristics were similar between the two (see Table 2).

TABLE 2 IFCT-0501 patient characteristics

Of the 451 patients analyzed, overall survival was significantly longer in patients treated with the combination therapy vs those in the single-agent arm (10.3 months vs 6.2 months, P = .0004). Survival at one year was 45.1% for arm A vs 26.9% for arm B.

VANTAGE POINT

MARK G. KRIS, MD Four-month improvement is significant

The 2009 ASCO guidelines state that age should not be used as a criterion for choosing therapy. The data from the French Intergroup study supports the idea that people over 70 should be offered the same kind of treatment as younger patients, said Dr. Kris, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center in New York.

"The average age of a person with lung cancer in the U.S. today is 71 years," Dr. Kris said. "These data tell us exactly what we need to know about most patients with lung cancer in this country, and these data help inform our decisions about these patients."

He added that "a four-month improvement is a huge one. Other large clinical and cooperative trials have generally [been viewed as] practice-changing with two-month improvement in median survival, so I think this four-month improvement in our largest population of patients [with lung cancer] is very important."

TABLE 3 Noteworthy NSCLC trials

Toxicity with the combination therapy was acceptable, according to Dr. Quoix. There were more instances of moderate to severe neutropenia with the combination therapy compared with the single-agent therapy (47.8% vs 12.2%). As expected, she said, there was more neurotoxicity in arm A, with nine toxic deaths vs three toxic deaths in arm B.

VANTAGE POINT

MARTIN EDELMAN, MD Rethink the standard of care in some, but not all, older patients

In the major lung cancer trials to date, the median age for of the subjects has been 62, but the majority of lung cancer patients today are 70 and over. "There are significant physiologic differences and frequent comorbidities in the elderly that make the applicability of these studies of younger patients questionable in the older age group," said Dr. Edelman, who is a professor of medicine at the University of Maryland Greenebaum Cancer Center in Baltimore.

Dr. Edelman and colleagues conducted a review of the SEER database and found that the majority of older lung cancer patients receive single-agent therapy (J Clin Oncol 28:2191-2197, 2010).

But in advanced disease, combination chemotherapy has conclusively demonstrated [itself] to be superior to single-agent cisplatin, he said. "Lung cancer is a disease of the elderly. Are these patients treated any differently than others? Should they be treated differently?"

The results from the French group clearly "support combination therapy for fit elderly patients," Dr. Edelman said. "This trial should change day-to-day practice and, once again, shows that there are benefits to the use of platinum-based combinations in this disease."

Dr. Edelman cautioned that the results should be not overextended as applying to all elderly patients; oncologists must be selective when deciding whether an older patient is a suitable candidate. The subjects in this trial were in good health, and while the combination treatment achieved superior efficacy, it came at a price of increased toxicity and mortality due to treatment, he said.

Dr. Edelman said that he was not "enthusiastic" about the choice of regimen in the experimental arm. "Carboplatin-paclitaxel, for better or worse, has been the comparative regimen since the mid-1990s in younger patients, but it has no real advantages over a number of other combinations and some disadvantages, most notably alopecia, myalgia, and neuropathy," he noted.

"I would have preferred to see a study with a single agent, either gemcitabine or vinorelbine. A more intellectually satisfying study would have compared [gemcitabine or vinorelbine] to carboplatin and the same agent," he explained.

Also, the standard carboplatin-paclitaxel [regimen] is typically administered every three weeks; not the weekly dosing utilized in this study. "However, weekly paclitaxel was shown to be similarly effective and better tolerated, and I agree with this choice," he said.

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Additional reporting by Shalmali Pal.