AOCNP EXAM 2026 COMPREHENSIVE
REVIEW QUESTIONS & VERIFIED
ANSWERS (A+ GUARANTEE)
1. A 55-year-old female with metastatic HER2-low breast cancer (IHC 1+ or 2+/ISH-) has
progressed on first-line endocrine therapy and a CDK4/6 inhibitor. According to the DESTINY-
Breast04 data, which of the following is the most appropriate next-line targeted therapy?
A. Trastuzumab deruxtecan (T-DXd)
B. Trastuzumab emtansine (T-DM1)
C. Sacituzumab govitecan
D. Lapatinib plus capecitabine
Answer: A
Conceptual Explanation: Trastuzumab deruxtecan (T-DXd) is the first HER2-directed
therapy to show a significant survival benefit in patients with HER2-low metastatic breast
cancer who have received prior chemotherapy or progressed on endocrine therapy.
2. Which of the following genetic polymorphisms is most strongly associated with an
increased risk of severe, life-threatening toxicity (e.g., neutropenic sepsis, severe diarrhea)
from fluoropyrimidines such as 5-Fluorouracil (5-FU) or Capecitabine?
A. UGT1A1*28
,B. TPMT deficiency
C. CYP2D6 poor metabolizer status
D. DPYD deficiency
Answer: D
Conceptual Explanation: Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting
enzyme in the catabolism of 5-FU. Patients with DPYD variants are at high risk for severe
toxicity. UGT1A1 is associated with irinotecan, CYP2D6 with tamoxifen, and TPMT with
thiopurines.
3. An oncology nurse practitioner is managing a patient with Grade 3 immune-related colitis
secondary to pembrolizumab. After 48 hours of IV methylprednisolone (1-2 mg/kg/day), the
patient shows no clinical improvement. What is the next recommended step in management?
A. Increase the steroid dose to 4 mg/kg/day
B. Continue IV steroids for another 5 days before changing therapy
C. Switch to oral prednisone and discharge
D. Initiate infliximab or vedolizumab
Answer: D
Conceptual Explanation: For steroid-refractory immune-related colitis (no improvement
within 48-72 hours), the prompt initiation of a biological agent such as infliximab or
vedolizumab is recommended by ASCO/NCCN guidelines.
, 4. In the context of Multiple Myeloma, which of the following cytogenetic abnormalities is
classified as ‘high-risk’ according to the Revised International Staging System (R-ISS)?
A. t(11;14)
B. t(6;14)
C. Hyperdiploidy
D. t(4;14)
Answer: D
Conceptual Explanation: High-risk cytogenetics in Multiple Myeloma include del(17p),
t(4;14), and t(14;16). t(11;14) is generally considered standard risk.
5. Which of the following represents a major diagnostic criterion for Hemophagocytic
Lymphohistiocytosis (HLH) in an adult patient receiving CAR-T cell therapy?
A. Isolated lymphocytosis
B. Hypofibrinogenemia (< 1.5 g/L)
C. Hypertension
D. Hypoferritinemia
Answer: B
Conceptual Explanation: HLH/MAS is a severe inflammatory syndrome. Diagnostic
criteria include high fever, splenomegaly, cytopenias, hypertriglyceridemia, and
hypofibrinogenemia. Ferritin is typically extremely elevated, not low.
REVIEW QUESTIONS & VERIFIED
ANSWERS (A+ GUARANTEE)
1. A 55-year-old female with metastatic HER2-low breast cancer (IHC 1+ or 2+/ISH-) has
progressed on first-line endocrine therapy and a CDK4/6 inhibitor. According to the DESTINY-
Breast04 data, which of the following is the most appropriate next-line targeted therapy?
A. Trastuzumab deruxtecan (T-DXd)
B. Trastuzumab emtansine (T-DM1)
C. Sacituzumab govitecan
D. Lapatinib plus capecitabine
Answer: A
Conceptual Explanation: Trastuzumab deruxtecan (T-DXd) is the first HER2-directed
therapy to show a significant survival benefit in patients with HER2-low metastatic breast
cancer who have received prior chemotherapy or progressed on endocrine therapy.
2. Which of the following genetic polymorphisms is most strongly associated with an
increased risk of severe, life-threatening toxicity (e.g., neutropenic sepsis, severe diarrhea)
from fluoropyrimidines such as 5-Fluorouracil (5-FU) or Capecitabine?
A. UGT1A1*28
,B. TPMT deficiency
C. CYP2D6 poor metabolizer status
D. DPYD deficiency
Answer: D
Conceptual Explanation: Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting
enzyme in the catabolism of 5-FU. Patients with DPYD variants are at high risk for severe
toxicity. UGT1A1 is associated with irinotecan, CYP2D6 with tamoxifen, and TPMT with
thiopurines.
3. An oncology nurse practitioner is managing a patient with Grade 3 immune-related colitis
secondary to pembrolizumab. After 48 hours of IV methylprednisolone (1-2 mg/kg/day), the
patient shows no clinical improvement. What is the next recommended step in management?
A. Increase the steroid dose to 4 mg/kg/day
B. Continue IV steroids for another 5 days before changing therapy
C. Switch to oral prednisone and discharge
D. Initiate infliximab or vedolizumab
Answer: D
Conceptual Explanation: For steroid-refractory immune-related colitis (no improvement
within 48-72 hours), the prompt initiation of a biological agent such as infliximab or
vedolizumab is recommended by ASCO/NCCN guidelines.
, 4. In the context of Multiple Myeloma, which of the following cytogenetic abnormalities is
classified as ‘high-risk’ according to the Revised International Staging System (R-ISS)?
A. t(11;14)
B. t(6;14)
C. Hyperdiploidy
D. t(4;14)
Answer: D
Conceptual Explanation: High-risk cytogenetics in Multiple Myeloma include del(17p),
t(4;14), and t(14;16). t(11;14) is generally considered standard risk.
5. Which of the following represents a major diagnostic criterion for Hemophagocytic
Lymphohistiocytosis (HLH) in an adult patient receiving CAR-T cell therapy?
A. Isolated lymphocytosis
B. Hypofibrinogenemia (< 1.5 g/L)
C. Hypertension
D. Hypoferritinemia
Answer: B
Conceptual Explanation: HLH/MAS is a severe inflammatory syndrome. Diagnostic
criteria include high fever, splenomegaly, cytopenias, hypertriglyceridemia, and
hypofibrinogenemia. Ferritin is typically extremely elevated, not low.
