In unselected patients with lung cancer, first line immunotherapy with durvalumab or the combination of durvalumab and tremelimumab does not improve overall survival, according to late breaking results from the MYSTIC trial presented at the ESMO Immuno-Oncology Congress.
The combination of immune checkpoint inhibitors and chemotherapy has been successfully tested in different trials as first line therapy for metastatic non-small cell lung cancer (NSCLC) while the use of two immunotherapy drugs without chemotherapy has been addressed in very few studies. The MYSTIC trial enrolled 1,118 patients with metastatic NSCLC who were randomly allocated to durvalumab alone, durvalumab plus tremelimumab, or chemotherapy. The primary endpoints were overall survival for durvalumab versus chemotherapy, and overall survival and progression free survival for durvalumab plus tremelimumab versus chemotherapy in patients with 25% or greater PD-L1 expression in tumour cells.
A total of 488 patients (44%) had PD-L1 expression of 25% or greater. Durvalumab alone or with tremelimumab did not improve overall survival or progression free survival compared to chemotherapy. Study author Dr Naiyer Rizvi, director of thoracic oncology and immunotherapeutics, Columbia University Medical Center, New York, US, said: "While not reaching statistical significance, durvalumab monotherapy gave a clinically meaningful median overall survival improvement of 16.3 months compared to 12.9 months with chemotherapy in patients with 25% or greater PD-L1 expression."
Rizvi said: "The results of the exploratory analysis need to be validated in a future trial. TMB is measured with a simple blood test and might be an easy way to select patients for this treatment. The CheckMate 227 trial previously showed that first line immunotherapy combinations work best in advanced NSCLC patients with high TMB." (3)
Safety data were consistent with previous studies. The incidence of grade 3/4 treatment-related adverse events was 14.6%, 22.1% and 33.8% with durvalumab, durvalumab plus tremelimumab, and chemotherapy, respectively.
"Immunotherapy has rapidly become a first line treatment option in NSCLC, as shown in the 2018 ESMO Clinical Practice Guidelines for metastatic disease," said Garrido, head of the Thoracic Tumour Section, Medical Oncology Department, Ramón y Cajal University Hospital, Madrid, Spain. (4) "The ESMO Immuno-Oncology Congress showcases cutting edge developments in this fast moving field, such as the highly anticipated MYSTIC trial. The analysis shows that appropriate biomarkers are needed to select the patients most likely to benefit from combination immunotherapy in first line. The challenge now is to prospectively validate them prior to implementation in clinical practice."