Combination therapies: Where are we in 2018?

Prof. Martin Reck (German Center for Lung Research, Germany) cited recent data from landmark trials to promote immunotherapy combined with other treatment options. “We have suggestions of multiple interactions and potential synergies,” said Prof. Reck at a mini-symposium on the Future of IO. These include immunotherapy plus chemotherapy, targeted therapies, and anti-VEGF therapy. In addition, a broad range of immuno-oncology agents can be combined to boost efficacy.

In squamous cell NSCLC, the practice-changing KEYNOTE-407 trial showed significantly increased overall survival (OS) with immunotherapy plus chemotherapy. The median OS was 15.9 months in the pembrolizumab group vs 11.3 months in the chemotherapy-alone group (HR 0.64; P=0.0008) [4].

According to Prof. Reck, efficacy was independent from PD-L1 status and there were no increases in immune-related adverse events (AEs) despite differences in the trial populations. OS outcomes were similar in phase 3 randomised trials of combination therapy for metastatic non-squamous cell NSCLC.

The KEYNOTE-189 trial reported an estimated OS rate of 69.2% in the pembrolizumab-combination group vs 49.4% in the placebo-combination group (HR 0.49; P<0.001) [5]. The IMpower150 trial found that adding atezolizumab to bevacizumab plus chemotherapy significantly improved OS (19.2 vs 14.7 months; HR 0.78; P=0.016). The outcome was independent from PD-L1 expression or EGFR or ALK genetic alteration [6].

Prof. Reck noted that while immunotherapy combinations benefit selected populations, convincing evidence for combining immunotherapy and targeted therapies has yet to be found. “AE rates have been unexpectedly high, but evaluation and clinical trials are ongoing,” he said. According to Prof. Reck, predictive markers are urgently needed to extend the benefits of combination therapies to more patients. Other issues being studied include the effects of sequencing on outcomes and the use of immunotherapy combinations as maintenance treatments.