Role of maintenance chemotherapy

Maintenance therapy is started immediately after first line therapy with aims of prolonging tumour response or stable disease.

Trials using bevacizumab in combination with first line platinum based chemotherapy have continued bevacizumab as maintenance therapy after completion of four to six cycles of chemotherapy. In the pivotal randomised phase III trial comparing paclitaxel and carboplatin chemotherapy alone vs. paclitaxel carboplatin bevacizumab, addition of bevacizumab was shown to improve OS (12.3 months vs. 10.3 months HR 0.79 95% CI 0.67 0.92 p = 0.003), progression free survival (6.2 months vs. 4.5 months HR 0.66 95% CI 0.57 0.77 p < 0.001) and response rates (35% vs. 15% p < 0.001) in patients with advancednon-squamous NSCLC. 215 of 407 (53%) patients continued with bevacizumab monotherapy with 107 (50%) receiving more than five cycles of monotherapy. 27

Maintenance pemetrexed has been studied in two large trials.33-35Switch maintenance was examined in a randomised double-blinded international study where monotherapy pemetrexed versus placebo was commenced following four cycles of platinum based chemotherapy. A switch to pemetrexed maintenance significantly improved progression free survival (4.3 months vs. 2.6 months HR 0.5 95% CI 0.42 0.61 p 0.0001) and OS (13.4 months vs. 10.6 months HR 0.79 95% CI 0.65 0.95 p = 0.012).34In the PARAMOUNT trial, 539 advanced non squamous non small cell lung cancer patients who received four cycles of pemetrexed-cisplatin induction therapy with no disease progression were randomly assigned to receiving continuation maintenance with pemetrexed plus best supportive care or with placebo plus best supportive care. Final OS analysis showed a statistically significantly longer OS of 13.9 months versus 11 months (unadjusted HR 0.78 95% CI 0.64 0.96 p = 0.0195). In this trial, maintenance pemetrexed was well tolerated with no new safety findings.35

Cost Effectiveness

Cost effectiveness of pemetrexed as first-line maintenance therapy was assessed by an American group as well as NICE. The American paper showed that in the subgroup of patients with non squamous histology, the incremental cost per life year gained was USD $122,371 when compared to observation. 36The ICERs as estimated by the manufacturers model submitted to NICE were USD $51,289 per QALY for the non squamous population.37

Recommendations on the Role of Maintenance Chemotherapy

1. In patients with good performance status of 0-1, continuation of pemetrexed is unanimously recommended in non-squamous NSCLC if stable disease or response is seen following induction chemotherapy (Level 1, B).

2. In patients with non squamous histology and good performance status of 0-1, should first line chemotherapy be non-pemetrexed based, then switch of maintenance to pemetrexed can be considered (Level 1, B).

3. In patients with all histologies, switch to erlotinib can be considered (Level 1, B). However, the workgroup recommends this only if a sensitizing EGFR mutation is detected (workgroup consensus).