Stages IIA and IIB NSCLC Treatment
Evidence (adjuvant radiation therapy):
- A meta-analysis, based on the results of ten randomized controlled trials and 2,232 individuals, reported the following:
- An 18% relative increase in the risk of death for patients who received PORT compared with surgery alone (HR, 1.18; P = .002). This is equivalent to an absolute detriment of 6% at 2 years (95% CI, 2%–9%), reducing OS from 58% to 52%. Exploratory subgroup analyses suggested that this detrimental effect was most pronounced for patients with stage I/II, N0–N1 disease, whereas for patients with stage III, N2 disease there was no clear evidence of an adverse effect.
- Results for local (HR, 1.13; P = .02), distant (HR, 1.14; P = .02), and overall (HR, 1.10; P = .06) recurrence-free survival similarly showed a detriment of PORT.[Level of evidence: 1iiA]
Further analysis is needed to determine whether these outcomes can potentially be modified with technical improvements, better definitions of target volumes, and limitation of cardiac volume in the radiation portals.
The preponderance of evidence indicates that postoperative cisplatin combination chemotherapy provides a significant survival advantage to patients with resected stage II NSCLC. Preoperative chemotherapy may also provide survival benefit. The optimal sequence of surgery and chemotherapy and the benefits and risks of postoperative radiation therapy in patients with resectable NSCLC remain to be determined.
After surgery, many patients develop regional or distant metastases. Several randomized, controlled trials and meta-analyses have evaluated the use of postoperative chemotherapy in patients with stage I, II, and IIIA NSCLC.[7,8,9,10,11,12,13]
Evidence (adjuvant chemotherapy):
- Data on individual patient outcomes were collected and pooled into a meta-analysis from the five largest trials (4,584 patients) that were conducted after 1995 of cisplatin-based chemotherapy in patients with completely resected NSCLC.
- With a median follow-up time of 5.2 years, the overall HR of death was 0.89 (95% CI, 0.82–0.96; P = .005), corresponding to a 5-year absolute benefit of 5.4% from chemotherapy.
- The benefit varied with stage (test for trend, P = .04; HR for stage IA, 1.40; 95% CI, 0.95–2.06; HR for stage IB, 0.93; 95% CI, 0.78–1.10; HR for stage II, 0.83; 95% CI, 0.73–0.95; and HR for stage III, 0.83; 95% CI, 0.72–0.94).
- The effect of chemotherapy did not vary significantly (test for interaction, P = .11) with the associated drugs, including vinorelbine (HR, 0.80; 95% CI, 0.70–0.91), etoposide or vinca alkaloid (HR, 0.92; 95% CI, 0.80–1.07), or other drugs (HR, 0.97; 95% CI, 0.84–1.13).
- The greater effect on survival observed with the doublet of cisplatin plus vinorelbine compared with other regimens should be interpreted cautiously as the total dose of cisplatin received was significantly higher in patients treated with vinorelbine.
- The meta-analysis as well as the individual studies [7,14] support the administration of postoperative cisplatin-based chemotherapy in combination with vinorelbine.
- The LACE pooled analysis (NCT00576914), ANITA trial, and NCIC-CTG JBR.10 trial (NCT00002583) all reported superior OS for the trial population as well as for the patients with stage II disease (pooled HR, 0.83; 95% CI, 0.73–0.95; HR, 0.71; 95% CI, 0.49–1.03; HR, 0.59; 95% CI, 0.42–0.85, respectively).
- Chemotherapy effect was higher in patients with better performance status (PS).
- There was no interaction between chemotherapy effect and any of the following:
- Type of surgery.
- Planned radiation therapy.
- Planned total dose of cisplatin.
- In a retrospective analysis of a phase III trial of postoperative cisplatin and vinorelbine, patients older than 65 years were found to benefit from treatment.
- Chemotherapy significantly prolonged OS for elderly patients (HR, 0.61; 95% CI, 0.38–0.98; P = .04).
- There were no significant differences in toxic effects, hospitalization, or treatment-related death by age group, although elderly patients received less treatment.
- Several other randomized controlled trials and meta-analyses have evaluated the use of postoperative chemotherapy in patients with stage I, II, and IIIA NSCLC.[7,8,9,10,11,12,13]