Targeted Therapy — MCQs
Which among the following drugs is the new FDA approved immune checkpoint inhibitor for endometrial carcinoma?
What is true about HER2/neu overexpression in cancer?
Ranibizumab is a monoclonal antibody against?
A 52-year-old female patient presents with HER-2 positive breast cancer that has become resistant to trastuzumab treatment. The oncologist is considering the next line of treatment for the patient. Which of the following options would be the most appropriate choice?
All are true regarding Sunitinib except which of the following?
Which of the following is a monoclonal antibody used in cancer treatment?
What is the most appropriate next step in management for a patient with a Stage III ovarian cancer with partial response to platinum-based chemotherapy?
What is the treatment for HER-2 positive trastuzumab resistant breast cancer?
Mechanism of action of Abatacept is?
Treatment with Herceptin in breast cancer is indicated for
Targeted Therapy Indian Medical PG Practice Questions and MCQs
Question 1: Which among the following drugs is the new FDA approved immune checkpoint inhibitor for endometrial carcinoma?
- A. Ipilimumab
- B. Pembrolizumab (Correct Answer)
- C. Trastuzumab
- D. Nivolumab
Explanation: **Pembrolizumab** * **Pembrolizumab** (Keytruda), a **PD-1 inhibitor**, received accelerated FDA approval for patients with **advanced endometrial carcinoma** that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), and has progressed following prior systemic therapy or is not a candidate for curative surgery or radiation. * This approval was based on data from the KEYNOTE-158 study, demonstrating **durable responses** in these specific subsets of endometrial cancer, highlighting its role in precision oncology. *Ipilimumab* * **Ipilimumab** (Yervoy) is a **CTLA-4 inhibitor** primarily approved for the treatment of **melanoma** and renal cell carcinoma, often in combination with nivolumab. * While it is an immune checkpoint inhibitor, its primary indications and specific FDA approvals do not include **endometrial carcinoma**. *Trastuzumab* * **Trastuzumab** (Herceptin) is a **monoclonal antibody** that targets the **HER2 protein**, commonly used in the treatment of **HER2-positive breast cancer** and certain types of gastric cancer. * It is not an immune checkpoint inhibitor and its mechanism of action is distinct from blocking immune checkpoints like PD-1 or CTLA-4. *Nivolumab* * **Nivolumab** (Opdivo) is a **PD-1 inhibitor** with broad FDA approvals for various cancers, including melanoma, non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, and others. * While a potent immune checkpoint inhibitor, **pembrolizumab** received the specific accelerated approval for advanced endometrial carcinoma in the context described, making it the most direct answer for the "new FDA approved" status in this specific indication.
Question 2: What is true about HER2/neu overexpression in cancer?
- A. Good prognosis
- B. Responds well to taxanes
- C. Responds well to monoclonal antibodies (Correct Answer)
- D. Seen in various cancers, including breast cancer
Explanation: ***Responds well to monoclonal antibodies*** - HER2/neu overexpression is targeted by **monoclonal antibodies** like trastuzumab (Herceptin), improving treatment outcomes [1]. - These therapies are specifically designed to **inhibit HER2-positive** tumors, leading to better overall prognosis compared to those without such therapies [1]. *Good prognosis* - HER2/neu overexpression is generally associated with a **poor prognosis** due to increased aggressiveness of the cancer. - It correlates with **higher rates of recurrence** and metastasis compared to HER2-negative breast cancers. *Responds well to taxanes* - While taxanes are commonly used in breast cancer treatment, HER2/neu positivity does not specifically imply a good response. - Response rates may not significantly differ based on HER2 status for taxane-based therapies alone. *Seen only in breast cancer* - HER2/neu overexpression can also occur in other cancers, such as **gastric and gastroesophageal junction cancers**. - It is not exclusive to breast cancer, though it is most commonly studied in this context [1].
Question 3: Ranibizumab is a monoclonal antibody against?
- A. VEGF (Correct Answer)
- B. Interleukin-6
- C. Cluster of Differentiation 20
- D. Epidermal Growth Factor Receptor
Explanation: ***VEGF*** - **Ranibizumab** is a **monoclonal antibody** specifically designed to inhibit **vascular endothelial growth factor A (VEGF-A)**. - By binding to VEGF-A, ranibizumab prevents its interaction with receptors on endothelial cells, thereby inhibiting **angiogenesis** and reducing vascular permeability, which is crucial in treating conditions like **wet age-related macular degeneration (AMD)** and **diabetic macular edema**. *Interleukin-6* - **Interleukin-6 (IL-6)** is a **pro-inflammatory cytokine** involved in various autoimmune and inflammatory diseases. - Monoclonal antibodies targeting IL-6, such as **tocilizumab**, are used in conditions like **rheumatoid arthritis** and **cytokine release syndrome**, not for ocular neovascularization. *Cluster of Differentiation 20* - **Cluster of Differentiation 20 (CD20)** is a protein found on the surface of **B lymphocytes**. - Monoclonal antibodies against CD20, like **rituximab**, are used in the treatment of **B-cell lymphomas**, **leukemia**, and certain **autoimmune diseases**, not for conditions requiring anti-VEGF therapy. *Epidermal Growth Factor Receptor* - The **epidermal growth factor receptor (EGFR)** is a **tyrosine kinase receptor** involved in cell growth and proliferation. - Monoclonal antibodies targeting EGFR, such as **cetuximab** and **panitumumab**, are used in the treatment of various **cancers**, particularly **colorectal cancer** and **head and neck cancer**.
Question 4: A 52-year-old female patient presents with HER-2 positive breast cancer that has become resistant to trastuzumab treatment. The oncologist is considering the next line of treatment for the patient. Which of the following options would be the most appropriate choice?
- A. Vemurafenib
- B. Erlotinib
- C. Lapatinib (Correct Answer)
- D. Sorafenib
Explanation: ***Lapatinib*** - Lapatinib is an oral **dual tyrosine kinase inhibitor** that targets both **HER2** and **EGFR** receptors, specifically approved for **trastuzumab-resistant HER2-positive breast cancer**. - Unlike trastuzumab (a monoclonal antibody that binds the extracellular domain), lapatinib inhibits the **intracellular tyrosine kinase domain** of HER2, providing an **alternative mechanism** to overcome resistance. - Often used in combination with capecitabine for patients who have progressed on trastuzumab-containing regimens. - **Clinical evidence**: The EGF100151 trial demonstrated efficacy in trastuzumab-refractory disease. *Vemurafenib* - Vemurafenib is a **BRAF V600E/K inhibitor** used primarily for **metastatic melanoma** with BRAF mutations. - It has **no activity against HER2** and is not indicated for breast cancer. - Would not provide benefit in this clinical scenario. *Erlotinib* - Erlotinib is a selective **EGFR tyrosine kinase inhibitor** used for **EGFR-mutant non-small cell lung cancer** and **pancreatic cancer** (with gemcitabine). - While it inhibits EGFR (which lapatinib also targets), erlotinib has **insufficient HER2 inhibition** to be effective in HER2-driven breast cancer. - Not approved or effective for trastuzumab-resistant HER2-positive breast cancer. *Sorafenib* - Sorafenib is a **multi-kinase inhibitor** targeting **RAF kinases, VEGFR-2/3, and PDGFR-β**, approved for **hepatocellular carcinoma, renal cell carcinoma, and thyroid cancer**. - It does **not specifically target HER2** signaling and has no established role in HER2-positive breast cancer. - Would not address the mechanism of disease in this patient.
Question 5: All are true regarding Sunitinib except which of the following?
- A. It inhibits tyrosine kinase receptors
- B. It is excreted primarily in urine (Correct Answer)
- C. It is used for the treatment of GIST
- D. It is used for renal cell carcinoma
Explanation: ***It is excreted primarily in urine*** - **Sunitinib** is predominantly metabolized in the **liver** by CYP3A4 and primarily excreted in the **feces**, not urine. - Its major active metabolite, N-desethyl sunitinib, is also primarily eliminated via the fecal route. *It inhibits tyrosine kinase receptors* - **Sunitinib** is a **multitargeted receptor tyrosine kinase (RTK) inhibitor**. - It blocks several RTKs involved in tumor growth, angiogenesis, and metastatic progression, such as **VEGFR, PDGFR, KIT, and FLT3**. *It is used for the treatment of GIST* - **Sunitinib** is approved for the treatment of **imatinib-refractory** or **imatinib-intolerant gastrointestinal stromal tumors (GIST)**. - Its mechanism in GIST involves inhibiting KIT and PDGFR, which are often mutated and constitutively active in this cancer. *It is used for renal cell carcinoma* - **Sunitinib** is a standard first-line treatment for **advanced renal cell carcinoma (RCC)**. - Its efficacy in RCC is primarily due to its inhibition of VEGFR, which targets the high vascularity characteristic of kidney tumors.
Question 6: Which of the following is a monoclonal antibody used in cancer treatment?
- A. Cisplatin
- B. Rituximab (Correct Answer)
- C. 5-fluorouracil
- D. Methotrexate
Explanation: ***Rituximab*** - **Rituximab** is a **chimeric monoclonal antibody** that targets the **CD20 protein** found on the surface of normal and malignant **B lymphocytes**. - It is widely used in the treatment of various **lymphomas** and **leukemias**, as well as autoimmune diseases, by inducing the death of CD20-positive B cells. *Cisplatin* - **Cisplatin** is a **platinum-based chemotherapy drug** that works by forming **DNA adducts**, leading to DNA damage and apoptosis of cancer cells. - It is used in various solid tumors but is not a monoclonal antibody; it's a **cytotoxic agent**. *5-fluorouracil* - **5-fluorouracil (5-FU)** is an **antimetabolite chemotherapy drug** that interferes with DNA and RNA synthesis, thereby inhibiting cell division. - It is a **pyrimidine analog** and not a monoclonal antibody. *Methotrexate* - **Methotrexate** is a **folate analog antimetabolite** that inhibits **dihydrofolate reductase**, interfering with DNA synthesis and cell proliferation. - It's a conventional chemotherapy agent and immunosuppressant, not a monoclonal antibody.
Question 7: What is the most appropriate next step in management for a patient with a Stage III ovarian cancer with partial response to platinum-based chemotherapy?
- A. Bevacizumab
- B. Perform surgery (Correct Answer)
- C. Switch to radiotherapy
- D. Continue regimen
Explanation: ***Perform surgery (Interval Debulking Surgery)*** - In **Stage III ovarian cancer**, after an initial partial response to **platinum-based chemotherapy**, **interval debulking surgery** is the standard next step to remove residual disease. - This approach aims to reduce tumor burden to an optimal level (< 1 cm residual disease), which has been shown to improve overall survival in multiple trials (EORTC 55971, GOG-152). - Performed after 3-4 cycles of neoadjuvant chemotherapy when the patient has demonstrated response and is medically fit for surgery. *Bevacizumab* - **Bevacizumab** is an **anti-angiogenic agent** used in ovarian cancer, typically as part of frontline maintenance therapy or for recurrent disease, not as the immediate next step after partial response to primary chemotherapy when surgery is feasible. - While it can be incorporated into maintenance treatment post-surgery, it's not the primary next step after partial response when interval debulking surgery is indicated. *Switch to radiotherapy* - **Radiotherapy** has a limited role in the primary treatment of advanced ovarian cancer due to its widespread peritoneal nature. - It is sometimes used for localized recurrence or symptom palliation, but not as a standard next step after partial response to chemotherapy in Stage III disease. *Continue regimen* - Continuing the same regimen after only a **partial response** is generally not the most effective strategy when further tumor reduction via surgery is possible. - The goal in advanced ovarian cancer is **maximal cytoreduction**, and if residual disease is present after neoadjuvant chemotherapy, interval debulking surgery is preferred over continued chemotherapy alone.
Question 8: What is the treatment for HER-2 positive trastuzumab resistant breast cancer?
- A. Sorafenib
- B. Lapatinib (Correct Answer)
- C. Vemurafenib
- D. Erlotinib
Explanation: ***Lapatinib*** - Lapatinib is a **dual tyrosine kinase inhibitor** that targets both **HER-2** and **epidermal growth factor receptor (EGFR)**, acting as a **small molecule inhibitor** that binds to the intracellular domain of these receptors. - Unlike trastuzumab (a monoclonal antibody targeting the extracellular domain), Lapatinib's **intracellular mechanism of action** allows it to overcome common mechanisms of trastuzumab resistance, such as receptor truncation or masking of the extracellular epitope. - It is specifically approved for the treatment of **HER-2 positive metastatic breast cancer** in combination with capecitabine after progression on trastuzumab-containing regimens. *Sorafenib* - Sorafenib is a **multi-kinase inhibitor** primarily targeting RAF, VEGFR, and PDGFR, and is used in renal cell carcinoma and hepatocellular carcinoma. - It does not specifically target HER-2 and is **not indicated** for HER-2 positive trastuzumab-resistant breast cancer. *Vemurafenib* - Vemurafenib is a **BRAF inhibitor** used for treating BRAF V600E mutation-positive melanoma. - This drug has no direct indications or demonstrated efficacy for **HER-2 positive breast cancer** and does not address trastuzumab resistance mechanisms. *Erlotinib* - Erlotinib is an **EGFR tyrosine kinase inhibitor** primarily used for non-small cell lung cancer with activating EGFR mutations. - While it targets EGFR, it does **not effectively target HER-2** and lacks the dual inhibition necessary to overcome trastuzumab resistance in HER-2 positive breast cancer.
Question 9: Mechanism of action of Abatacept is?
- A. T cell inhibitor (Correct Answer)
- B. TNF-alpha inhibitor
- C. Calcineurin inhibitor
- D. IL-1 inhibitor
Explanation: ***T cell inhibitor*** * **Abatacept** works by blocking the **costimulatory signal (CD28-CD80/86)** required for full T-cell activation, acting as a **selective T-cell costimulation modulator** [1]. * This inhibition prevents T-cell proliferation and cytokine production, thereby reducing inflammation in autoimmune diseases. * *TNF-alpha inhibitor* * **TNF-alpha inhibitors** like etanercept or infliximab bind to and neutralize **tumor necrosis factor-alpha (TNF-alpha)**, a key pro-inflammatory cytokine. * While effective in similar conditions, this is a different mechanism of action than Abatacept's direct T-cell modulation. * *Calcineurin inhibitors* * **Calcineurin inhibitors** such as cyclosporine and tacrolimus block the activity of **calcineurin**, an enzyme essential for T-cell activation and cytokine production. * This inhibition primarily prevents **interleukin-2 (IL-2)** transcription, which is crucial for T-cell proliferation, but differs from Abatacept's blocking of costimulation. * *IL-1 inhibitor* * **IL-1 inhibitors** like anakinra target and block the action of **interleukin-1 (IL-1)**, another potent pro-inflammatory cytokine. * This class of drugs is used for conditions driven by IL-1, but their mechanism is distinct from Abatacept's focus on T-cell costimulation.
Question 10: Treatment with Herceptin in breast cancer is indicated for
- A. Tumours with over-expressed HER2/C-erbB-2 protein (Correct Answer)
- B. PR receptor +ve tumours
- C. ER receptor +ve tumours
- D. Ki-67 stain +ve tumours
Explanation: **tumours with over-expressed C-erb B-2 protein** - **Herceptin** (trastuzumab) is a monoclonal antibody that specifically targets the **HER2/neu receptor**, which is encoded by the *ERBB2* gene. - Its efficacy depends on the **overexpression of C-erbB-2 protein** (also known as HER2/neu) on the surface of breast cancer cells, which indicates **HER2-positive breast cancer**. *K : 67 stain +ve tumours* - **Ki-67** is a proliferation marker that indicates the **growth fraction of a tumor**, and a positive stain suggests a rapidly dividing tumor. - While Ki-67 positivity is associated with more aggressive tumors, it does **not directly indicate suitability for Herceptin** treatment. *PR receptor +ve tumours* - Tumors positive for the **progesterone receptor (PR)** are typically treated with **hormonal therapies**, such as tamoxifen or aromatase inhibitors. - **PR positivity** does not indicate responsiveness to Herceptin, which targets the HER2 receptor. *ER receptor +ve tumours* - Tumors positive for the **estrogen receptor (ER)** are also treated with **hormonal therapies** due to their dependence on estrogen for growth. - Similarly to PR-positive tumors, **ER positivity** does not determine eligibility for Herceptin therapy.
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