First-line chemotherapeutic options for advanced Non- Small Cell Lung Cancer (NSCLC) with no driver mutation

Systemic platinum based doublet chemotherapy is the preferred initial treatment option for patients with advanced NSCLC, good performance status and without a driver mutation. Chemotherapy in fit patients has been conclusively shown in a meta-analysis to improve OS when compared to best supportive care (HR 0.77 95% CI 0.71 0.83 p 0.01).25A randomised study comparing four platinum based chemotherapy regimens showed no significant advantage of one regimen over the other.26More recently, evidence from a phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed showed similar efficacy, median OS (10.3 vs. 10.3 months HR 0.94 95% CI 0.84 1.05) with better tolerability.2Importantly, a pre-specified analysis of OS by treatment arm demonstrated a significantly better survival in patients with adenocarcinoma and large cell carcinoma treated with pemetrexed/cisplatin as compared to gemcitabine/cisplatin (12.6 months vs. 10.9 months HR 0.84 95% CI 0.71 0.99 p = 0.03).

Subsequent trials have shown additional survival benefit with the addition of biologic agents such as bevacizumab. The Eastern cooperative oncology group (ECOG) conducted a randomised study which showed a significant survival benefit of adding bevacizumab to paclitaxel plus carboplatin in the treatment of select patients with non squamous NSCLC.27A systemic review and meta-analysis of trials adding bevacizumab to platinum based chemotherapy in first line treatment further confirms this survival benefit.28

The role of cetuximab, an EGFR monoclonal antibody in the first line treatment for advanced NSCLC remains to be defined and has not been approved for use in this patient population.29, 30

Cost Effectiveness

In a systematic review and economic evaluation of the clinical effectiveness and cost effectiveness of first line chemotherapy for advanced NSCLC, the preferred drugs for patients with advanced NSCLC are paclitaxel followed by gemcitabine and subsequently docetaxel.31In patients with non-SCC disease, pemetrexed/cisplatin is cost effective with USD $53,238 per QALY gained.31In a cost-utility assessment of bevacizumab, the ICER of bevacizumab and chemotherapy when compared with chemotherapy alone was USD $560,000 per QALY.32Bevacizumab thus does not appear to be cost effective when added to chemotherapy. There is no local data with regard to the cost effectiveness of chemotherapy and or bevacizumab.

Recommendations on First Line Chemotherapeutic Options for Advanced NSCLC Negative for Driver Mutation

1. In fit patients, platinum doublet chemotherapy is unanimously recommended in the first line treatment of advanced NSCLC (category 1).

2. In view of better outcomes with the use of pemetrexed in non-squamous histology and in considering cost effectiveness, the workgroup is of the opinion that pemetrexed/platinum chemotherapy is preferable in the first line treatment of non-squamous advanced NSCLC (workgroup consensus).

3. Bevacizumab when added to chemotherapy is an option (category 2A).

4. The use of bevacizumab as well as pemetrexed is limited to those non squamous in histology.

5. There is insufficient evidence to support the use of cetuximab for which the workgroup unanimously does not recommend in this setting (workgroup consensus).