Jul 24, 2023
Question 1: Breast Cancer
A 68-year-old woman was treated for stage III, triple-positive breast cancer with doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab (ACTH) in the adjuvant setting. She then developed symptomatic congestive heart failure (CHF) with a left ventricular ejection fraction of 30%. She now presents to your clinic with newly metastatic breast cancer to her liver. A percutaneous liver biopsy confirms metastatic triple-positive disease without a PIK3CA mutation. Her New York Heart Association (NYHA) class is II. The patient is under the care of a cardiologist and is taking a β-blocker and furosemide. Brain MRI is positive for metastatic disease. She would like to have the most aggressive treatment possible.
Docetaxel, carboplatin, and trastuzumab (TCH)
Tucatinib, capecitabine, and trastuzumab
Neratinib and capecitabine
Question 2: Melanoma
A 45-year-old man presented with a growing lesion on his right upper arm. Biopsy of the lesion revealed melanoma with a Breslow depth of 4.2 mm and ulceration. PET/CT scan and brain MRI did not show any distant metastases. He underwent a wide local excision and lymphoscintigraphy, with pathology showing complete excision of melanoma. Two sentinel lymph nodes from the right axilla were removed, both with a 1-mm deposit of melanoma. The tumor did not show a BRAF V600 mutation. His Eastern Cooperative Oncology Group (ECOG) performance status is 0.
Adjuvant anti-PD1 immunotherapy
Adjuvant radiation therapy
Completion lymph node dissection (CLND)
Question 1 Rationale and References
Correct answer: D. Neratinib and capecitabine
Rationale: CHF is a common adverse effect of HER2-targeted antibodies; this is sometimes reversible, but when the left ventricular ejection fracture is below 50%, the risk of exacerbating CHF with additional HER2 antibodies is unacceptable. A patient with symptomatic CHF should receive tyrosine kinase inhibitor–based therapy to best control metastatic HER2-positive breast cancer. The three tyrosine kinase inhibitors currently available for metastatic breast cancer are lapatinib, neratinib, and tucatinib. The NALA trial demonstrated a median progression-free survival of 8.8 months and an overall survival of 24 months for patients with metastatic HER2-positive breast cancer with brain metastases. The HER2climb trial also demonstrated efficacy of a tucatinib-based regimen; however, that regimen contained trastuzumab, for which this patient is not eligible based on her CHF.
- Saura C, Oliveira M, Feng YH, et al. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: phase III NALA trial. J Clin Oncol. 2020;38(27):3138-49. DOI: https://doi.org/10.1200/JCO.20.00147
- Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer [published correction appears in N Engl J Med. 2020 Feb 6;382(6):586]. N Engl J Med. 2020;382(7):597-609. DOI: https://doi.org/10.1056/NEJMoa1914609
Question 2 Rationale and References
- Eggermont AMM, Blank CU, Mandala M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med. 2018;378(19):1789-801. DOI: https://doi.org/10.1056/NEJMoa1802357
- Ascierto PA, Del Vecchio M, Mandalá M, et al. Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial [published correction appears in Lancet Oncol. 2021 Oct;22(10):e428]. Lancet Oncol. 2020;21(11):1465-1477. DOI: https://doi.org/10.1016/S1470-2045(20)30494-0