Test your knowledge of melanoma and sarcomas with two multiple-choice questions from the ASCO Self-Evaluation Program (ASCO-SEP) on ASCO Education.
Correct answers are listed at the bottom of the page.
Question 1: Melanoma
A 65-year-old man presents in the clinic with unintentional weight loss, palpable right axillary lymph nodes, and fatigue. He has a history of stage IIA malignant melanoma of the back. Three years ago, a wide local excision and sentinel lymph node biopsy was completed. The Eastern Cooperative Oncology Group performance status is 1. Cross-sectional imaging of the chest, abdomen, and pelvis demonstrates numerous nodules in the bilateral lung and liver and right axillary adenopathy, suggestive of metastatic disease. Biopsy of a right axillary lymph node reveals metastatic melanoma without a BRAF mutation. Laboratory findings are unremarkable, except for a lactate dehydrogenase level of 500 U/L.
What is the most appropriate option for first-line treatment?
- Nivolumab with ipilimumab
- Encorafenib with binimetinib
- High-dose interleukin 2 (IL2)
Question 2: Sarcomas
A 48-year-old man presents to the local emergency department with complaints of vague abdominal pain. He reports symptoms of increasing fatigue, early satiety, and intermittent nausea over the past six months. He gets easily short of breath with minimal activities. He has no significant medical problems and takes no prescription medications. Physical examination reveals a palpable liver edge as well as palpable abdominal masses on deep palpation. Laboratory studies are unremarkable except for a hemoglobin level of 8.5 g/dL (normal range: 12-15.5 g/dL). CT imaging of the abdomen and pelvis, with contrast, reveals radiographic evidence of multifocal abdominal and peritoneal disease, including multiple liver metastases. Ultrasonography-guided biopsy of a liver lesion reveals an epithelioid appearing mesenchymal tumor; immunohistochemistry findings are consistent with a gastrointestinal stromal tumor (GIST). Molecular testing reveals the presence of a PDGFRA exon 18 mutation, specifically D842V. He is referred to you for a new patient consultation.
Which of the following should you recommend now?
Question 1 Rationale and References
Correct answer: A. Nivolumab with ipilimumab
Rationale: In patients with a good performance status without a BRAF V600 activating mutation, the best initial choice for treatment is a combination (PD-1 inhibitor/CTLA4 inhibitor) or a single-agent PD1 inhibitor therapy. In this case, the patient's tumor does not have a BRAF V600E activating mutation, which precludes encorafenib with binimetinib. The combination of PD1 inhibitor therapy and CTLA4 inhibitor therapy showed overall survival superiority compared with either agent alone in CheckMate 067. High-dose IL2 was the first treatment for metastatic melanoma with a median OS of 11.4 months; however, given the improved responses with new agents and a higher toxicity profile of high-dose IL2, it is now a less preferred approach.
Hodi FS, Chiarion-Sileni V, Gonzalez R, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomized, phase 3 trial [published correction appears in Lancet Oncol. 2018 Dec;19(12):e668] [published correction appears in Lancet Oncol. 2018 Nov;19(11):e581]. Lancet Oncol. 2018;19(11):1480-92. DOI: https://doi.org/10.1016/S1470-2045(18)30700-9
Weber JS, Gibney G, Sullivan RJ, et al. Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): an open-label, randomized, phase 2 trial [published correction appears in Lancet Oncol. 2016 Jul;17 (7):e270]. Lancet Oncol. 2016;17(7):943-55. DOI: https://doi.org/10.1016/S1470-2045(16)30126-7
Question 2 Rationale and References
Correct answer: D. Avapritinib
Rationale: A GIST is the most common mesenchymal tumor of the GI tract. The epithelioid appearance is often seen in GIST tumors with a PDGFRA D842V mutation. The presence of these mutations conveys resistance to imatinib, sunitinib, and regorafenib—agents approved inGIST with KIT and PDGFRA (non-D842V) mutations. Avapritinib is an oral small molecular inhibitor FDA-approved for GIST with exon 18 mutations, including D842V.
Heinrich MC, Jones RL, von Mehren M, et al. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial [published correction appears in Lancet Oncol. 2020 Sep;21(9):e418]. Lancet Oncol. 2020;21(7):935-46. DOI: https://doi.org/10.1016/S1470-2045(20)30269-