CD8+ T Shows possibility in Treatment of SCLC

Release Date: 23-Sep-2019

The Phase II of clinical trial of immune checkpoint inhibitors gives a possibility of treatment of patients with small cell lung cancer (SCLC). The activity of combination of durvalumab and olaparib were observed in all the patients where tumor had an inflamed phenotype.


According to the Anish Thomas, author of this study, tumor CD8-positive T-cell infiltration has been linked to antitumor activity in patients with advanced melanoma and NSCLC treated with immune checkpoint inhibitors. Our observation extends these findings to relapsed SCLC and suggests that a preexisting CD8-positive T-cell response may be predictive of benefit from immune checkpoint inhibitorandndash;based therapies in SCLC.


In the open labeled, single-arm phase II trial, patients with SCLC were treated with the combination of durvalumab plus olaparib. To be eligible, patients had to have histologically confirmed SCLC with at least 1 prior platinum-based chemotherapy regimen received. Patients also had to have an ECOG performance status of 2 or lower with adequate organ and bone marrow function.


The patients with a previous immune checkpoint inhibitor were not excluded from the study, while those who had received prior treatment with a PARP inhibitor were excluded. Additionally, those with symptomatic brain metastases, autoimmune disease, pneumonitis, interstitial lung disease, or inflammatory bowel disease were also excluded from the trial.


The dose selected for the trial was 1500 mg of durvalumab intravenously every 28 days and 300 mg olaparib tablets twice daily on a continuous basis. Some of the adverse effects are also observed during the study. The most common adverse events reported in this study included anemia (80%), lymphopenia (60%), leukopenia (50%), fatigue (45%), and thrombocytopenia (45%).


Nine patients experienced grade 3/4 treatment-related AEs, including anemia, lymphopenia, thrombocytopenia, and hypophosphatemia. Additionally, 25% of patients experienced an increase in thyroid-stimulating hormone levels, which were asymptomatic. There were no other neurological or immune-related AEs reported. Only 1 patient required a dose reduction of olaparib due to grade 3 anemia. No patients discontinued treatment due to AEs.


According to the Thomas, the defining biomarkers predictive of response in SCLC is challenging because in this disease, biopsies are generally not performed at relapse and biopsy specimens usually provide limited tissue for analyses.


This trail was limited as the same size is small and due to the single-arm design. There were no comparator groups, which limits the ability to assess both the clinical and biomarker response to the combination. Analysis of a large cohort is necessary to confirm the result of the report and identify patients who are beneficial by the immune checkpoint inhibitor therapy.    


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