Lung Cancer Health Center

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Neoadjuvant therapy

Neoadjuvant chemotherapy

The role of chemotherapy prior to surgery in patients with stage III-N2 NSCLC has been extensively tested in clinical trials. The proposed benefits of preoperative (neoadjuvant) chemotherapy include the following:

• A reduction in tumor size that may facilitate surgical resection.
• Early eradication of micrometastases.
• Better tolerability.

Evidence:

1. The Cochrane Collaboration group provided a systematic review and meta-analysis of seven randomized controlled trials that included 988 patients and evaluated the addition of preoperative chemotherapy to surgery versus surgery alone.[3] These trials evaluated patients with stages I, II, and IIIA NSCLC.
   1. Preoperative chemotherapy provided an absolute benefit in survival of 6% across all stages of disease from 14% to 20% at 5 years (HR = 0.82; 95% CI, 0.69-0.97; P = .022).[3][Level of evidence: 1iiA]
   2. This analysis was unable to address questions such as whether particular types of patients may benefit more or less from preoperative chemotherapy.[4]
2. In the largest trial reported to date, 519 patients were randomly assigned to receive either surgery alone or three cycles of platinum-based chemotherapy followed by surgery.[5] Most patients (61%) had clinical stage I disease, 31% had stage II disease, and 7% had stage III disease.
   1. Postoperative complications were similar between groups, and no impairment of quality of life was observed.
   2. There was no evidence of a benefit in terms of overall survival (OS) (HR = 1.02; 95% CI, 0.80-1.31; P = .86)
   3. Updating the systematic review by addition of the present result suggests a 12% relative survival benefit with the addition of preoperative chemotherapy (1,507 patients, HR = 0.88; 95% CI, 0.76-1.01; P = .07), equivalent to an absolute improvement in survival of 5% at 5 years.[5]

Adjuvant therapy

Adjuvant chemotherapy

Patients with completely resected stage IIIA NSCLC may benefit from postoperative cisplatin-based chemotherapy.[6][Level of evidence: 1iiA]

Evidence:

Evidence from randomized controlled clinical trials indicates that when stage IIIA NSCLC is encountered unexpectedly at surgery, chemotherapy given after complete resection improves survival.

Several randomized controlled trials and meta-analyses have evaluated the use of postoperative chemotherapy in patients with stage I, II, and IIIA NSCLC.[6,7,8,9,10,11,12]

1. 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.[6]
   1. 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.
   2. 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).
   3. The benefit varied with stage (HR for stage IIIA = 0.83; 95% CI, 0.72-0.94).
   4. The greater effect on survival observed with the doublet of cisplatin plus vinorelbine compared with other regimens should be interpreted with caution as the total dose of cisplatin received was significantly higher in patients treated with vinorelbine.
2. Two trials (FRE-IALT and ANITA) reported significant OS benefits associated with postoperative chemotherapy in stage IIIA disease.[4,8]
   1. For the subgroup of stage IIIA patients in ANITA (n = 325), the HR was 0.69 (95% CI, 0.53-0.90), and the result for the FRE-IALT trial (n = 728) was HR = 0.79 (95% CI, 0.66-0.95).
   2. Chemotherapy effect was higher in patients with a better performance status (PS).
   3. There was no interaction between the chemotherapy effect and any of the following:
      • Sex.
      • Age.
      • Histology.
      • Type of surgery.
      • Planned radiation therapy.
      • Planned total dose of cisplatin.
3. 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.[13]
   1. Chemotherapy significantly prolonged OS for elderly patients (HR = 0.61; 95% CI, 0.38-0.98; P = .04).
   2. There were no significant differences in toxic effects, hospitalization, or treatment-related death by age group, although elderly patients received less treatment.