RESUMEN
BACKGROUND: Checkpoint-Inhibition has revolutionized the treatment for several entities such as melanoma and renal cell carcinoma. The first encouraging experience in ovarian cancer was reported for nivolumab, a fully humanized anti-programmed death-1 antibody. Pseudoprogression is a new phenomenon associated with these novel immuno-oncologic agents. It can be explained by infiltrating leucocytes and edema that result in a temporary increase in tumor size and delayed subsequent shrinkage due to tumor cell destruction. CASE SUMMARY: We report on a 47-year old patient with platinum-resistant ovarian cancer that was treated off-label with nivolumab 3mg/kg iv d1q14d. She first experienced classic pseudoprogression with inguinal lymph node swelling after cycle two and subsequent shrinkage. After 6 cycles she presented with rectal bleeding and progressive disease was diagnosed due to new tumor infiltration into the rectum. CONCLUSION: Clinicians should be aware of pseudoprogression, its underlying mechanisms and strategies to discriminate pseudo- from real progression in ovarian cancer.
RESUMEN
The introduction of checkpoint inhibitors revolutionized immuno-oncology. The efficacy of traditional immunotherapeutics, like vaccines and immunostimulants was very limited due to persistent immune-escape strategies of cancer cells. Checkpoint inhibitors target these escape mechanisms and re-direct the immune system to anti-tumor toxicity. Phenomenal results have been reported in entities like melanoma, where no other therapy was able to demonstrate survival benefit, before the introduction of immunotherapeutics. The first experience in ovarian cancer (OC) was reported for nivolumab, a fully human anti-programmed cell death protein 1 (PD1) antibody, in 2015. While the data are extraordinary for a mono-immunotherapeutic agent and very promising, they do not match up to the revolutionary results in entities like melanoma. The key to exceptional treatment response in OC, could be the identification of the most immunogenic patients. We hypothyse that BRCA mutation could be a predictor of improved response in OC. The underlying DNA-repair-deficiancy should result in increased immunogenicity because of higher mutational load and more neoantigen presentation. This hypothesis was not tested to date and should be subject to future trials. The present article gives an overview of the immunologic background of checkpoint inhibition (CI). It presents current data on nivolumab and other checkpoint-inhibitors in solid tumors and OC specifically and depicts important topics in the management of this novel substance group, such as side effect control, diagnostic PD-1/programmed cell death-ligand 1 (PD-L1) expression assessment and management of pseudoprogression.