Background
Although molecularly targeted therapies (MTT) given alone or in combination with chemotherapy have delivered proven survival benefit for many newly diagnosed cancers, there is little evidence of their efficacy in recurrent or late-stage settings. Late-stage cancers are considered mutationally diverse to benefit from MTTs therefore next generation (NGS) is discouraged in these patients. Therefore, the aim of this systematic review is to explore effectiveness and safety of MTTs in late-stage cancer.
Methods
We searched medical databases and trial registers for randomised control trials. Outcomes of interest were progression-free survival (PFS), overall survival (OS), adverse events and quality of life. We used random effects modelling to pool outcomes across studies and GRADE to assess the certainty of evidence.
Results
Thirty-seven studies including 9819 participants were included. Compared to standard therapy, MTTs showed improvement in PFS (hazard ratio (HR) = 0.66, 95% confidence interval (CI) 0.59-0.74; moderate‐certainty), no difference in OS (HR = 0.85, 95% CI 0.75-0.97; low‐certainty). Similarly, MTT in combination with standard therapy also significantly improved PFS (HR = 0.61, 95% CI 0.53–0.70, moderate‐certainty) as well as OS (HR = 0.79, 95% CI 0.70-0.89; moderate‐certainty). Matched targeted also showed improvement in PFS compared to non MTT (HR = 0.76, 95% CI 0.64-0.89; moderate‐certainty) and compared to best of supportive care (HR = 0.37, 95% CI 0.28-0.50; moderate‐certainty). There was limited evidence for the effect of MTT on overall survival for both the comparisons. Similarly, there was limited evidence for serious adverse events and quality of life for all the comparisons.
Conclusions
MTT guided by next‐generation sequencing in people with advanced cancer prolongs the time before cancer progresses compared to standard therapies. However, there is limited evidence to suggest that it prolongs overall survival, improves the quality of life or increases adverse events.