Adjuvant Platinum-Based Chemotherapy vs Observation in Non-Small Cell Lung Cancer: Meta-analysis of Trials with Intermediate- and Long-Term Follow-Up

ABSTRACT

Largely, earlier data of adjuvant chemotherapy following complete resection of non-small cell lung cancer (NSCLC) showed survival advantage. However, recent data with longer follow-up demonstrated conflicting results. The aim of this meta-analysis is to test whether the early positive survival advantage remains or fades with time. Included were 4 randomized clinical trials each with a follow-up of more than 6 years and involving 3,529 patients (1,750 and 1,779 patients in the adjuvant chemotherapy and observation arms, respectively). Patients’ median age ranged from 59 to 61 years and they were mostly males (65% to 87%). The analysis showed that adjuvant chemotherapy reduced mortality by 14% (HR = 0.86; 95% CI, 0.79 to 0.94; P = 0.0001). The overall survival (OS) benefit remained after adjustment for known prognostic variables. The OS advantage was shown for patients with stage II (HR = 0.80; 95% CI, 0.68 to 0.94, P = 0.008) and stage III (HR = 0.80; 95% CI, 0.69 to 0.92; P = 0.002) indicating 20% reduction in the risk of dying in those stages. On the other hand, no benefit was shown for patients with stage I (HR = 0.98; 95% CI, 0.85 to 1.14; P = 0.82). Similarly, chemotherapy significantly prolonged disease-free survival (DFS) as compared with observation with a risk reduction of 17% (HR = 0.83; 95% CI, 0.75 to 0.90; P < 0.0001). Analysis of DFS according to disease stage was limited due to lack of adequate data. Adjuvant chemotherapy was not associated with excessive non-lung cancer mortality (HR = 1.16; 95% CI, 0.93 to 1.45; P = 0.18). Only one trail reported adequate data on the pattern of recurrence with significant reduction in local (HR = 0.74; 95% CI, 0.61 to 0.90; P = 0.002) and distant (HR = 0.84; 95% CI, 0.72 to 0.98; P = 0.02) relapse. In stage IB disease, adjuvant chemotherapy improved OS (HR = 0.68; 90% CI, 0.51 to 0.90; P = 0.02) and DFS HR = 0.69; 90% CI, 0.49 to 0.97; P = 0.035) only for those with primary tumor size of ≥ 4 cm. The current meta-analysis that was based on large patient population followed-up for an appropriate intermediate and long duration have provided significant clinical conclusions concerning the benefits of adjuvant chemotherapy for resected NSCLC. In the future, other meta-analyses with even longer-term follow up may be necessary.

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