Doublet Chemo for Elderly NSCLC Patients Should Be Standard

Zosia Chustecka

June 08, 2010

June 8, 2010 (Chicago, Illinois) — A doublet of chemotherapy is the standard of care for patients with nonsmall-cell lung cancer (NSCLC) 65 years or younger, but for elderly patients there has been some debate over using this aggressive approach, and many clinicians use only a single-agent chemotherapy.

This should now change. Doublet chemotherapy should be the standard of care, no matter how old the patient is, according to experts here at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting.

Dr. Elisabeth Quoix

The conclusions are based on a phase 3 clinical trial presented at the plenary session by Elisabeth Quoix, MD, professor of medicine at the University Hospital in Strasbourg, France. The trial, one of the first devoted entirely to elderly patients, involved 451 patients with advanced NSCLC who were between the ages of 70 and 89.

The results showed significantly better overall survival in those treated with a doublet of carboplatin and paclitaxel than in those treated with a single agent — either gemcitabine or vinorelbine (10.4 vs 6.2 months; hazard ratio [HR], 0.60; P = .0001). There was also a significant improvement in progression-free survival, with patients treated with the doublet remaining disease-free for nearly twice as long as those treated with a single agent (6.6 vs 3.2 months; HR, 0.55; P < .0001).

The doublet was associated with more adverse effects than the single agents, in particular moderate to severe neutropenia (47.8% vs 12.2%), but the toxicity was "acceptable," Dr. Quoix said.

Doublet chemotherapy with monthly carboplatin and weekly paclitaxel offers a new paradigm for elderly patients with advanced NSCLC, Dr. Quoix concluded. The doubling of progression-free survival and the improvement in overall survival were both "very significant," she said, and were achieved at the expense of manageable toxicity.

Doublet chemotherapy should now be the standard of care for elderly patients, just as it is for younger patients with NSCLC, she told Medscape Oncology.

This trial should change day-to-day practice.

"This is an important and positive study," said Martin Edelman, MD, from the University of Maryland in Baltimore, who was the discussant for this study. The doublet chemotherapy approach was "demonstrated to be conclusively superior," he said.

"This trial should change day-to-day practice," Dr. Edelman said.

Change in Current Treatment

Currently, treatment guidelines from ASCO say that age should not be considered when deciding on treatment, and leaves a choice of using double or single chemotherapy to the physician, Dr. Edelman explained; the European guidelines specifically call for the use of single-agent chemotherapy.

Dr. Edelman noted that a review of the SEER database at the University of Maryland found that many clinicians do not use any chemotherapy in elderly patients with NSCLC, and those who do tend to choose single-agent chemotherapy, and not because of comorbidities. "This is in the United States, where we have a reputation for aggressive therapy, some would say too aggressive, so one can only imagine how this looks in the rest of the world," he said.

On the basis of the superiority shown in this trial, the more aggressive approach of doublet chemotherapy should be used in NSCLC no matter how old the patient is, he suggested. However, he cautioned that the patients in this trial were a "fit population, so we should not extend the results," adding that there was an increase in toxicity, "so we should be selective."

It will inform our decisions in clinical practice.

"This is an important abstract because it will inform our decisions in clinical practice," said Mark Kris, MD, chief of the Thoracic Oncology Service at Memorial Sloan-Kettering Cancer Center in New York City, who was moderating a press briefing at which the study was highlighted.

"The average age of a patient with lung cancer is 71 years," he pointed out. About half of all patients diagnosed with NSCLC in the United States each year are more than 70 years old, which amounts to 100,000 patients, he said.

This trial showed an improvement in overall survival of 4 months with the doublet, compared with single-agent chemotherapy. In the past, clinical trials that have shown an improvement of 2 months have been considered practice-changing, he said.

This trial shows that age per se should not be used as a criterion for making a decision about chemotherapy, he said, but added that comorbidities must be taken into account.

Dr. Quoix reports serving in a consultancy or advisory role for Lilly and Roche, and reports relationships with Roche, Lilly, and Pierre-Fabre Medicament. Dr. Kris reports acting as a consultant or advisor to AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck, Novartis, and Pfizer.

American Society of Clinical Oncology (ASCO) 2010 Annual Meeting: Abstract 2. Presented June 6, 2010.