NEW ORLEANS—In elderly non-small-cell lung cancer (NSCLC) patients, the combination of gemcitabine(Drug information on gemcitabine) (Gem-zar) plus vinorelbine (Navelbine) yields better survival than vinorelbine alone, according to the final analysis of a Southern Italy Cooperative Oncology Group (SICOG) phase III trial. Giuseppe Frasci, MD, of the National Tumor Institute, Naples, Italy, reported the results at the 36th Annual Meeting of the American Society of Clinical Oncology (ASCO).
The trial evaluated survival and quality of life in a comparison of combined gemcitabine 1,200 mg/m² plus vinorel-bine 30 mg/m² on days 1 and 8 every 3 weeks vs vinorelbine alone at the same dose and schedule. The rationale for the study was the need for less toxic regimens for use in elderly patients.
“Many people are concerned about the use of cisplatin(Drug information on cisplatin)-based chemotherapy in the elderly,” Dr. Frasci pointed out. Studies have found the risk of death within 30 days of chemotherapy in patients over 70 to be many times greater than the risk in middle-aged patients.
The combination was selected based on data showing that single-agent vino-relbine produced good response rates and median survival with moderate toxicity, and that the activity of gemcitabine was not impaired in an elderly subset.
Pilot studies found the combination to be safe in patients over 70, which led to the current trial in patients aged 71 to 85 years with stage IV NSCLC or stage III disease with malignant pleural effusion or supraclavicular nodal involvement. Central nervous system involvement was allowed if patients were not symptomatic.
Survival was the primary endpoint, and quality of life was validated by a formal quality-of-life scale. The study was terminated early because a significant benefit emerged during the interim analysis in favor of the combination.
The study enrolled 152 patients. Dr. Frasci presented survival data on the first 120 patients at 14-month median follow-up. At that time, 19 patients were alive in the combination arm vs 8 in the single-agent vinorelbine control arm.
The combination regimen proved superior in that it improved survival and maintained quality of life. Median survival was 29 weeks in the combination arm vs 18 weeks in the control arm (P < .01). Probable 1-year survival was about 30% in the combination arm vs about 10% in the vinorelbine arm.
There were no complete responses in either arm. Partial responses were noted in 22% of patients in the combination arm and 15% in the vinorelbine arm.
Evidence that combination treatment maintained a better quality of life was provided by the finding of a prolonged time to symptom deterioration: 21 weeks for the combination vs 13 weeks for vinorelbine alone (P = .002).
More patients in the combination arm displayed some improvement in symptoms during treatment. In fact, the number of patients without symptom deterioration in 6 months was double in the combination arm, 43% vs 22%. At the conclusion of therapy, 62% of gemcita-bine/vinorelbine patients reported quality of life to be improved or stable, compared with 40% on vinorelbine alone, Dr. Frasci reported.
The toxicity profiles were not significantly different, although numerically the combination arm had more neutropenia (38% vs 28%) and thrombocytopenia (13% vs 8%).
Performance status (PS) clearly affected outcome. Among patients with PS 2, the percentage of patients stopping treatment before two cycles was 59%. Their median survival was 19 weeks vs 26 weeks for patients with PS 0-1, he said.
Comparison With ELVIS Results
Dr. Frasci pointed out that the vinorelbine control arm in this study did not fare as well as the vinorelbine arm in the earlier ELVIS trial (Elderly Lung Cancer Vinorelbine Italian Study). In that study, patients receiving vinorelbine plus best supportive care survived 28 weeks, compared with 21 weeks for best supportive care alone.
“The easiest explanation is that the two populations are not as similar as they appear at first glance,” he suggested. The current study, as compared to the ELVIS trial, included more patients with brain metastases, who did particularly poorly in the vinorelbine arm, and more patients with comor-bidities, whose survival was worse.
“We can say on the basis of these results that the addition of gemcitabine to vinorelbine produced more than a 60% increase in median survival time,” Dr. Frasci concluded. “Gemcitabine/vino-relbine is now considered first-line treatment in the elderly with NSCLC in our group, but we don’t think that the single-agent approach should be avoided in these patients.” In fact, he said, the Italian group has begun a randomized trial to test two single-agent arms—gemcitabine or pacli-taxel [Taxol]—and two doublets—gemcitabine/vinorelbine and gemcitabine/paclitaxel.
David Gandara, MD, the session’s discussant, remarked that the study had a number of strengths, although the sample size was small due to early closure, and the control arm performed “particularly poorly compared to previous trials in the same population.”
He said that “since the trial targeted the elderly and the comparator was vinorelbine alone, it does not establish nonplatinum therapy or this nonplat-inum regimen as superior or even equal to platinum-containing regimens for general use.” In poor-risk patients, he said, “two potential avenues to tolerable therapy that also provide clinical benefit are the use of nonplatinum regimens and sequential single agents.”
