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August 3, 2017. Interim results of the MYSTIC trial were reported this week. Spoiler alert: there was no improvement in progression free survival (PFS) among previously untreated patients with Stage IV NSCLC (without EGFR or ALK aberrations) with first-line immunotherapy versus same-ole platinum-based chemo. The Phase III MYSTIC trial opened in 2015 and randomized 1118 patients to receive durvalumab (novel PD-L1 inhibitor) vs durvalumab + tremelimumab (CTLA inhibitor) vs platinum-based chemo. Neither the mono- or combo immunotherapy arms met prespecified thresholds of PFS benefits, even among patients with >25% of tumor expressing PD-L1. These disappointing results are in contrast to improvements seen with targeted therapies in place of chemo for NSCLC patients with EGFR mutations (erlotinib) or ALK oncogenes (alectinib) as well as successes seen with durvalumab’s predecessor pembrolizumab in a similar population as the one included in MYSTIC. AstraZeneca is still holding out for overall survival outcomes, but unless something MYSTICal happens...we’re not holding our breath.