ALK inhibitor therapy achieved “remarkable” response rates in a small study of patients with ALK-positive adult-onset neuroblastoma. Some patients who did not respond to initial treatment with 1 ALK inhibitor had a subsequent response to lorlatinib (Lorbrena), which had the best showing among ALK inhibitors evaluated in this setting. The results of this retrospective study were presented at the American Society of Clinical Oncology 2021 virtual annual meeting.
“Adult-onset neuroblastoma is a rare cancer that is challenging to treat, because patients cannot tolerate the chemotherapy regimens used on children. ALK is an appealing drug target and use of an ALK inhibitor can be a well-tolerated option for treatment of these patients, improving response and time to disease progression,” said lead investigator Jessica Stiefel, MD, Third Year Pediatric Hematology/Oncology Fellow, Memorial Sloan Kettering Cancer Center, New York City.
“Our experience shows that development of resistance to 1 ALK inhibitor does not preclude use of other agents within the same drug class. Overall, ALK-targeted therapy appears to be a safe and effective option for adult-onset neuroblastoma and should be considered when making this diagnosis,” she added.
Neuroblastoma typically occurs in children, with a median onset at age 5, and is usually treated with chemotherapy and radiation. Adult-onset neuroblastoma is a rare and biologically distinct cancer compared with childhood neuroblastoma.
“Adult-onset neuroblastoma is metastatic, chemotherapy-resistant, and almost invariably fatal,” Dr Stiefel explained. “The presence of ALK mutations in adult-onset neuroblastoma provides an opportunity for targeted therapy for a disease that is otherwise very challenging to treat.”
Dr Stiefel presented data from a retrospective review based on 23 adult patients with adult-onset neuroblastoma who were genetically sequenced at Memorial Sloan Kettering Cancer Center between 2014 and 2020. Fourteen (61%) patients were found to harbor ALK somatic mutations. Of these 14, 7 were treated with 1 or more FDA-approved ALK inhibitors. Her presentation focused on these 7 patients.
One patient was diagnosed with the disease at age 12 years, and the other 6 at ages ranging from 28 to 68 years. Patients were treated with 1 to 4 previous regimens. Most had measurable disease at treatment initiation and had metastatic disease at diagnosis. Previous multimodality treatment included surgery, chemotherapy, and radiation.
Overall, treatment with ALK inhibitors was well-tolerated. Dizziness, drowsiness, and hallucinations were reported in 1 patient each, and these effects resolved when treatment was stopped. Grade 1 nausea and vomiting were reported in 6 patients. Treatment discontinuations were reported in 4 patients taking crizotinib (Xalkori) and alectinib (Alecensa).
“Lorlatinib was the best tolerated ALK inhibitor,” Dr Stiefel said. “No patient receiving lorlatinib required discontinuation due to adverse events, and 1 required a dose reduction.”
All 7 patients had an initial response to an ALK inhibitor, but 6 discontinued due to progressive disease or adverse events (3 each). Median time to progression was 15.5 months. Median overall survival was 46.5 months (range, 17-74 months).
Four patients treated with more than 1 ALK inhibitor continued to be in response and were started on lorlatinib therapy after disease progression on other ALK inhibitors. Two patients had stable disease.