In comparing survival among 3 treatment periods (1982–1988, 1989–1995, and 1996–2002) in patients with advanced nonsmall cell lung cancer enrolled in phase 3 trials of first-line systemic chemotherapy, as Bearz and colleagues suggested, we noticed the potential interference of the heterogeneity of trial characteristics, with a large proportion of patients with poor performance status and with stage IV disease and a number of randomized patients across each trial.1 This is a critical issue in our analysis. To minimize such influence, we conducted a multivariate analysis for survival, adjusting for these confounding factors that could affect patient survival. It is of note that after adjusting these factors, the year of trial initiation still influenced patient survival significantly (P < .0001 for median survival time and P < .0130 for time to progression). Therefore, we can say that our findings support the common feeling pointed out by Bearz et al. that the overall survival in patients with advanced nonsmall cell lung cancer slightly improved.
The potential influence of second-line chemotherapy is also an important point in assessing the effect of first-line chemotherapy, and such salvage therapy may contribute to recent survival improvement, as Bearz et al. commented. However, its effect on survival was significant but, indeed, quite modest.2 Furthermore, in our study, the survival prolongation was observed regarding median time to progression after the initiation of first-line chemotherapy, considered not to be affected by effects of the second-line treatment.
Finally, we now truly realize that such survival improvement over the years is quite modest, with only a few days increase per year, and we are far from satisfied with this modest survival improvement. Throughout our reporting, we did not intend to stress only significance of survival improvement with passage of time. Rather, we emphasized quite limited survival-time improvement in the article, and we concluded, and still consider, that novel targets and new agents are needed for future fights against advanced nonsmall cell lung cancer.