The only curative intervention for early-stage (I-IIIA) non–small-cell lung cancer (NSCLC) is surgical resection. Yet, despite optimal surgical care, the chance of recurrence and death due to NSCLC is high.1,2 Adjuvant (postoperative) and neoadjuvant (preoperative) treatment with chemotherapy has prolonged survival in select patients with early-stage NSCLC in both prospective trials and systemic meta-analyses. This chapter summarizes the evidence supporting the use of adjuvant and neoadjuvant therapy for patients with early-stage NSCLC. It also highlights the areas where more research is needed and explores ongoing research strategies to optimize both patient and treatment selection to achieve the best outcome for this patient population.
Early evidence for a benefit of adjuvant chemotherapy in resected NSCLC resulted from a large meta-analysis of 52 randomized trials of adjuvant cisplatin-based therapy, which reported a trend toward improvement in 5-year survival of roughly 5% (HR = 0.87; 95% CI, 0.74–1.02; p = 0.08).3 These results prompted numerous subsequent prospective trials to assess the benefit of adjuvant chemotherapy. The study population, treatment, and outcome information from the studies enrolling more than 300 patients and comparing surgery alone to surgery followed by chemotherapy is presented in Table 92-1.
Table 92-1ADJUVANT CHEMOTHERAPY TRIALS FOR NSCLC, INCLUDING LONG-TERM FOLLOW-UP RESULTS WHEN AVAILABLE |Favorite Table|Download (.pdf) Table 92-1ADJUVANT CHEMOTHERAPY TRIALS FOR NSCLC, INCLUDING LONG-TERM FOLLOW-UP RESULTS WHEN AVAILABLE
|TRIAL NAME ||STAGE ||NO. OF PATIENTS ||TREATMENT ||MEDIAN FOLLOW-UP (YEARS) ||HAZARD RATIO (HR) FOR DEATH ||p-VALUE |
|International Adjuvant Lung Trial (IALT)4,5 ||I-III ||1867 ||Cisplatin-based therapy (multiple doses, combined with vindesine, vinblastine, vinorelbine, or etoposide) vs. observation ||7.5 ||HR 0.91 (95% CI: 0.81–1.02) ||P = 0.10 |
|JBR.106,7 ||IB-II ||482 ||Cisplatin/vinorelbine vs. observation ||9.3 ||HR 0.79 (95% CI: 0.62–1.00) ||P = 0.05 |
|Adjuvant Navelbine International Trialist Association 01 (ANITA)8 ||I-IIIA ||840 ||Cisplatin and vinorelbine vs. observation ||6.3 ||HR: 0.80 (95% CI: 0.66–0.96) ||P = 0.017 |
|Adjuvant Lung Cancer |
Project Italy (ALPI)9
|I-IIIA ||1088 ||Cisplatin, mitomycin, and vindesine vs. observation ||5.4 ||HR 0.96 (95% CI: 0.81–1.13) ||P = 0.589 |
|Big Lung Trial (BLT)10 ||I-III ||307 ||Cisplatin (multiple regimens, including with vindesine, vinorelbine, mitomycin/ifosfamide, or mitomycin/vinblastine) vs. observation ||2.9* ||HR 1.02 (95% CI: 0.77–1.35) ||P = 0.90 |
|Cancer and Leukemia Group B (CALGB) 963312,13 ||IB ||344 ||Carboplatin and paclitaxel vs. observation ||9 ||HR 0.80 (95% CI: 0.63–1.02) ||P = 0.062 (one-tailed) |
Adjuvant Therapy Trials Showing a Difference in Survival
Three of the six trials listed in Table 92-1 reported a statistically significant survival advantage for the patients treated with chemotherapy after complete resection of their lung cancer. In the International Adjuvant Lung Trial (IALT), 1867 patients with completely resected stages I-IIIA NSCLC were randomly assigned ...