Long-term Follow-up Provides New Insights on Adjuvant Therapy for Lung Cancer
Longer-term follow-up reports from two large, randomized clinical trials of chemotherapy delivered after surgery in patients with non-small cell lung cancer (NSCLC) have yielded disparate results. Published online November 23, 2009, in the Journal of Clinical Oncology, the findings come 2 years after clinical guidelines strongly recommended the use of post-surgical, or adjuvant, chemotherapy in certain patients with NSCLC.
The initial reports from both trials, based on 5 years of follow-up, found that adjuvant chemotherapy resulted in a statistically significant improvement in overall survival compared with observation following surgery. With longer-term follow-up (a median of 9.3 years), results from the smaller of the two trials, JBR.10, continue to show a benefit from adjuvant chemotherapy, with an absolute improvement in overall survival of 11 percent compared with observation. The survival improvement was strongest for patients with stage II NSCLC.
However, in the other trial, called IALT, after 7.5 years of follow-up, the initial survival improvement was not sustained, although there was a small but statistically nonsignificant improvement in overall survival. This was due in large part to an excess of deaths unrelated to cancer in the patients who received chemotherapy compared with those in the observation arm. In the JBR.10 trial, the authors noted, there was no difference between the groups in the rate of death from other causes or second cancers.
The results demonstrate that “longer follow-up is needed in the adjuvant setting…to assess cure,” wrote Jean-Yves Douillard, M.D., of the Centre Rene Gauducheau in St. Herblain, France, in an accompanying editorial. Dr. Douillard explained that the JBR.10 trial only used the third-generation chemotherapy drug vinorelbine, along with cisplatin, whereas patients in the IALT trial received any of four chemotherapy agents along with cisplatin, including vinorelbine. In comparison with the other three agents (vindesine, vinblastine, and etoposide), he wrote, patients with lung cancer treated with vinorelbine have had a “consistent improvement in survival on a long-term basis.”
It is worrisome that the longer-term follow-up from the IALT trial did not show a sustained benefit, said Giuseppe Giaccone, M.D., Ph.D., head of the Medical Oncology Branch and Thoracic Oncology Section in NCI’s Center for Cancer Research. But some of the regimens used in the trial were “suboptimal,” he continued. Dr. Giaccone agreed with the recommendation on the adjuvant regimen of choice. “The largest experience is with cisplatin/vinorelbine,” he said, “and this is the regimen that should be used, unless there are contraindications.”