Aims

Systemic treatment for advanced NSCLC has changed radically the past years with the availability of new drug classes such as monoclonal antibodies, tyrosine kinase inhibitors and newer chemotherapies like pemetrexed. This has introduced complexity into treatment decisions and in particular, the relative efficacies of these treatments are not clear. The aim of this study was to establish and assess the evidence base of systemic treatments for advanced NSCLC following progression on first line therapy.

Methods

Clinical trials of systemic treatments for advanced NSCLC were identified by literature search using Embase. The search strategy was determined by two authors and reviewed by the third. Results were reviewed independently for inclusion with differences resolved by discussion. Data informing progression free survival (PFS) and overall survival (OS) were independently extracted then synthesised using meta-analysis.

Results

The search retrieved 249 results: 2 were duplicates; 164 were excluded on title and abstract review; 48 were excluded on full text review. 35 were included in the final analysis¹ informing 34 distinct comparisons. Compared to docetaxel monotherapy: crizotinib, aflibercept+docetaxel, nintendanib+docetaxel and vandetinib+docetaxel showed superiority in PFS (HR[95%CI]: 0.30 [0.21,0.43], 0.82 [0.72,0.93], 0.79 [0.68,0.92] and 0.78 [0.69,0.88] respectively); nintendanib+docetaxel showed superiority in OS (HR [95%CI]: 0.88 [0.78,0.99]). Compared to pemetrexed monotherapy: crizotinib, erlotinib+pemetrexed and gefitinib showed superiority in PFS (HR[95%CI]: 0.59 [0.43,0.81], 0.61 [0.47,0.79], 0.53 [0.36,0.78] respectively); erlotinib+pemetrexed showed superiority in OS (HR[95%CI]: 0.71 [0.53,0.95]). Compared to erlotinib monotherapy: bevacizumab and erlotinib+pemetrexed showed superiority in PFS (HR[95%CI]: 0.62 [0.52,0.74], 0.57 [0.40,0.81] respectively); erlotinib+chemotherapy showed superiority in OS (HR[95%CI]: 0.67 [0.49,0.92]).

Conclusions

Despite a large volume of studies, results herein suggest few interventions show superiority over standard of care comprising docetaxel, pemetrexed or erlotinib in terms of PFS and OS. Further differences may exist regarding comparative safety profiles and should be the subject for future research.