The Case of the Immunotherapy Inquiry, Part II
You may remember Jay, a 62-year-old man with inoperable stage IIIA non-small cell lung cancer (NSCLC) (https://voice.ons.org/news-and-views/immunotherapy-in-cancer-treatment), from the case study in the April 2017 issue of ONS Voice (https://voice.ons.org/news-and-views/immunotherapy-in-cancer-treatment). He was symptomatic with a persistent cough, unintentional weight loss, and fatigue.
Jay completes six weeks of chemoradiation with carboplatin and paclitaxel. His presenting symptoms resolve, and positron-emission tomography (PET) shows no evidence of disease. Unfortunately, a PET 10 months later reveals mediastinal lymphadenopathy, and a biopsy confirms metastatic squamous cell carcinoma. Jay begins treatment with an immune checkpoint inhibitor.
Immunotherapy Indicated as Second-Line Therapy
Immune checkpoint inhibitors are part of a large family of anticancer treatments collectively defined as immunotherapy because the drugs partner with the immune system to kill cancer cells. One of the hallmarks of cancer is its ability to inactivate T cells and hide from immune system recognition. Immune checkpoint inhibitors function by reactivating T cells through prevention of programed death protein (https://www.ncbi.nlm.nih.gov/pubmed/24690569) (PD-1) attachment to its ligands (PD-L1 and PD-L2) located on the tumor cell.
Jay did not initially qualify for immunotherapy with pembrolizumab—the only immunotherapeutic currently approved as first-line treatment in NSCLC—because his PD-L1 tumor proportion score (TPS) was only 5%. Pembrolizumab is approved in the first line setting for TPS ≥ 50% and as second line therapy for TPS ≥ 1%. PD-L1 testing is not required for use of nivolumab for patients (http://ascopubs.org/doi/abs/10.1200/jco.2015.63.8049) having failed a platinum-based therapy.
Jay initially had an excellent response to immunotherapy. He started golfing again and crafting in his woodshop. He continued with treatment with relatively few side effects for nine months, then presented to the clinic with severe diarrhea. He was given a course of high-does steroids for what his oncologist presumed was immune-mediated colitis secondary to the immunotherapy. After the diarrhea resolved, Jay tolerated another three treatments before developing grade 3 pneumonitis and disease progression. Immunotherapy was discontinued.
Immune-mediated adverse events, like those Jay experienced, are thought to result from an overproduction of cytokines in healthy tissues as a result of T-cell reactivation. Jay’s disease course, treatment options, and side-effect profile exemplify some of the benefits and challenges when using immunotherapy in cancer treatment.