Post-study immunotherapy in MYSTIC

Durvalumab is approved for the treatment of unresectable, stage 3 NSCLC and has shown clinical activity in heavily pre-treated patients with metastatic NSCLC in phase 2 and 3 trials [1,2]. MYSTIC is an open-label, phase 3 study evaluating first-line durvalumab with or without tremelimumab vs platinum-based chemotherapy in metastatic NSCLC.

In a previous analysis, presented at the 2018 ESMO I-O meeting, an improvement in OS was seen with durvalumab vs chemotherapy in patients with tumour cell PD-L1 expression ≥25% (see Figure; HR 0.76, P=0.036) [3]. The safety and tolerability profile of durvalumab was consistent with data from previous trials [1,2,4].

Figure: OS in patients with PD-L1 expression of ≥25%: primary endpoint of MYSTIC trial [3]



Figure kindly provided by Dr Reinmuth.

In the current analysis of MYSTIC, Dr Niels Reinmuth (Asklepios Lung Clinic, Munich-Gauting, Germany) described subsequent treatment patterns and explored the effect of subsequent immunotherapy on the OS outcome with durvalumab vs chemotherapy [5]. Among patients who received subsequent treatment, immunotherapy was administered to 14% of patients in the durvalumab group and 67% of patients in the chemotherapy group, so a markedly higher proportion of patients. This imbalance with respect to the subsequent policy may have confounded the primary OS outcome. The current exploratory analysis showed increased OS benefit with first-line durvalumab vs chemotherapy after adjusting for the effect of subsequent immunotherapy (see Figure; HR 0.66, P=0.002) [5]. More long-term data about the impact of immunotherapy on OS in this setting is needed.

1. Garassino MC, et al. Lancet Oncol. 2018;19:521-536.
2. Kowalski DM, et al. Ann Oncol. 2018;29(suppl_8):viii493-viii547.
3. Rizvi N, et al. Ann Oncol. 2018;29(suppl 10). Presented at ESMO I-O 2018, abstract LBA6.
4. Antonia SJ, et al. N Engl J Med. 2017;377:1919-1929.
5. Reinmuth N, et al. ELCC 2019, abstract LBA4.



Posted on 25 June 201915 March 2021