Consolidation Therapy For Stage III Non-Small Cell Lung Cancer
The standard of care for unresectable stage III NSCLC (large tumor with positive nodes) has been chemo radiotherapy sometimes followed by surgery if the combined modality is able to significantly downstage the cancer. Several phase III trials have shown that concurrent chemo/radiation has given better overall survival compared to sequential.
The most common chemotherapy regimens used in the US are cisplatin/etoposide or carboplatin/paclitaxel.
Many trials tried to add additional survival benefits by adding consolidation therapy. Trials with consolidation docetaxel, gefitinib or platinum drugs have failed to show improvement in survival. Subsequent trials with consolidation cetuximab failed as well.
Durvalumab is a human immunoglobulin G1 Kappa monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PDL1) with the PDI molecules. Durvalumab is a checkpoint inhibitor. The most common side effects have been cough, pneumonia, rash and hypothyroidism, arthralgia, diarrhea and decreased appetite. Grade 3 or 4 adverse events have been uncommon. The drug is mostly well tolerated.
The pacific trial tested consolidation therapy with durvalumab versus placebo following two cycles of chemo and radiotherapy. The durvalumab consolidation was given for 12 months. Disease-free survival more than doubled going from 5.6 months to 16.8 months. The survival benefit was seen in all patients across the board irrespective of the PDL1 status. Durvalumab reduced the incidence of distant metastasis. Time to development of distant metastasis was 23 months in the durvalumab arm compared to 14 months for the placebo arm. The results of the pacific trial changed the standard of care for unresectable NSCLC.