MCQ Quiz-Determining the Optimal Sequence of Therapies

MCQ Quiz: Determining the Optimal Sequence of Therapies

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In modern oncology, patients often have multiple effective treatment options available. This raises a critical clinical question: what is the best order in which to use them? Determining the optimal sequence of therapies is a complex challenge addressed by sophisticated clinical trials. For PharmD students, understanding how these trials are designed and how to interpret their results is essential for creating evidence-based, long-term treatment plans that maximize patient survival.

1. What is the primary clinical question addressed by a trial designed to determine the optimal sequence of therapies?

  • Whether Treatment A is superior to a placebo.
  • What the maximum tolerated dose of Treatment A is.
  • Whether Treatment A and Treatment B are bioequivalent.
  • Whether starting with Treatment A followed by Treatment B is better than starting with Treatment B followed by Treatment A.


Answer: Whether starting with Treatment A followed by Treatment B is better than starting with Treatment B followed by Treatment A.

2. In a trial designed to determine the optimal sequence of therapies, which of the following is often the most important primary endpoint?

  • Objective Response Rate (ORR)
  • Progression-Free Survival (PFS)
  • Overall Survival (OS)
  • Adverse event rate


Answer: Overall Survival (OS)

3. The DREAMseq trial investigated the optimal sequence of therapies for which specific patient population?

  • Patients with non-small cell lung cancer
  • Patients with advanced BRAF-mutant melanoma
  • Patients with triple-negative breast cancer
  • Patients with chronic myeloid leukemia


Answer: Patients with advanced BRAF-mutant melanoma

4. The two therapeutic strategies compared in the DREAMseq trial were:

  • Chemotherapy and radiation therapy
  • Targeted therapy (BRAF/MEK inhibitors) and immunotherapy (checkpoint inhibitors)
  • Surgery and targeted therapy
  • Immunotherapy and chemotherapy


Answer: Targeted therapy (BRAF/MEK inhibitors) and immunotherapy (checkpoint inhibitors)

5. A sequencing question becomes clinically relevant when:

  • There is only one effective treatment for a disease.
  • There are two or more effective, but mechanistically different, lines of therapy available.
  • No effective treatments exist for a disease.
  • A new drug is seeking its initial FDA approval.


Answer: There are two or more effective, but mechanistically different, lines of therapy available.

6. Why is Overall Survival (OS) a particularly strong endpoint for a sequencing trial?

  • It captures the effect of both the first-line therapy and subsequent therapies.
  • It is the earliest endpoint to occur.
  • It is a surrogate endpoint.
  • It is the easiest endpoint to measure.


Answer: It captures the effect of both the first-line therapy and subsequent therapies.

7. A trial designed to determine the optimal sequence of therapies is fundamentally asking a question about:

  • Short-term tumor shrinkage.
  • Long-term treatment strategy.
  • The maximum tolerated dose.
  • The safety of a drug in healthy volunteers.


Answer: Long-term treatment strategy.

8. In the DREAMseq trial, one arm started with dabrafenib plus trametinib, which represents what type of therapy?

  • Immunotherapy
  • Targeted therapy
  • Chemotherapy
  • Radiation therapy


Answer: Targeted therapy

9. The other arm in the DREAMseq trial started with nivolumab plus ipilimumab, which represents what type of therapy?

  • Immunotherapy
  • Targeted therapy
  • Chemotherapy
  • Hormone therapy


Answer: Immunotherapy

10. A key feature of a sequencing trial design is allowing for or specifying:

  • No treatment after the first line fails.
  • Crossover to the other treatment strategy upon disease progression.
  • The use of a placebo in the second line.
  • The immediate discontinuation of all therapy after the first line.


Answer: Crossover to the other treatment strategy upon disease progression.

11. Which factor might influence the choice of the initial therapy in a sequencing decision, beyond overall survival?

  • The speed of response (e.g., for a patient with a high tumor burden).
  • The toxicity profile of the first-line agent.
  • The potential for cross-resistance with subsequent therapies.
  • All of the above.


Answer: All of the above.

12. The results of the DREAMseq trial suggested that for patients with BRAF-mutant melanoma, the optimal sequence is to start with:

  • Targeted therapy followed by immunotherapy.
  • Immunotherapy followed by targeted therapy.
  • Chemotherapy alone.
  • Neither therapy, as both were ineffective.


Answer: Immunotherapy followed by targeted therapy.

13. A pharmacist interpreting the results of a sequencing trial should primarily focus on the difference in:

  • The objective response rate to the first-line therapy.
  • The median overall survival between the two sequence arms.
  • The cost of the first-line drugs.
  • The number of patients enrolled in each arm.


Answer: The median overall survival between the two sequence arms.

14. The topic “Determining the Optimal Sequence of Therapies” is a key component of what broader subject?

  • Advanced clinical trial evaluation
  • Sterile compounding
  • Pharmacy law
  • Drug information resources


Answer: Advanced clinical trial evaluation

15. If Sequence A (Drug X then Y) has a median OS of 30 months and Sequence B (Drug Y then X) has a median OS of 40 months, this suggests:

  • Sequence A is the optimal sequence.
  • Sequence B is the optimal sequence.
  • There is no difference between the sequences.
  • Neither drug is effective.


Answer: Sequence B is the optimal sequence.

16. Why might Progression-Free Survival (PFS) be a misleading endpoint in a sequencing trial?

  • A highly effective first-line therapy might produce a long PFS1, but if second-line therapy is ineffective, the overall survival could be poor.
  • PFS is not a valid endpoint in any oncology trial.
  • PFS and OS always produce identical results.
  • PFS is a measure of overall survival.


Answer: A highly effective first-line therapy might produce a long PFS1, but if second-line therapy is ineffective, the overall survival could be poor.

17. The clinical context for the DREAMseq trial reading is:

  • Early-stage, resectable melanoma.
  • Metastatic melanoma.
  • Adjuvant therapy for melanoma.
  • Prevention of melanoma.


Answer: Metastatic melanoma.

18. A challenge in conducting sequencing trials is that they often require:

  • A very short follow-up period.
  • A large number of patients and a long follow-up period to assess overall survival.
  • No statistical analysis.
  • Only healthy volunteers.


Answer: A large number of patients and a long follow-up period to assess overall survival.

19. A pharmacist applying the results of a sequencing trial to a patient must first confirm that:

  • The patient in front of them matches the inclusion criteria of the trial population (e.g., correct disease and biomarker status).
  • The patient has the same insurance as the trial participants.
  • The patient is the same age as the principal investigator.
  • The patient has read the clinical trial publication.


Answer: The patient in front of them matches the inclusion criteria of the trial population (e.g., correct disease and biomarker status).

20. The concept of sequencing implies that the choice of first-line therapy can impact:

  • Only the response to the first-line therapy.
  • The efficacy of subsequent lines of therapy.
  • The patient’s insurance coverage only.
  • The cost of the first-line drug only.


Answer: The efficacy of subsequent lines of therapy.

21. A major reason to favor immunotherapy first in the DREAMseq trial was its potential for:

  • Rapid tumor shrinkage in all patients.
  • A durable, long-lasting response in a subset of patients.
  • A better side effect profile compared to targeted therapy.
  • A lower cost.


Answer: A durable, long-lasting response in a subset of patients.

22. A major reason to favor targeted therapy first in BRAF-mutant melanoma is its:

  • High response rate and rapid onset of action, which is useful for symptomatic patients.
  • Ability to produce a long-lasting response in all patients.
  • Favorable toxicity profile with no side effects.
  • Low cost compared to immunotherapy.


Answer: High response rate and rapid onset of action, which is useful for symptomatic patients.

23. The design of a sequencing trial must account for what phenomenon in the control arm?

  • The placebo effect.
  • The effect of the active therapy that will be given upon progression (crossover).
  • Spontaneous remission.
  • Non-adherence.


Answer: The effect of the active therapy that will be given upon progression (crossover).

24. The question of optimal sequencing arises in many cancers, not just melanoma. It is relevant whenever:

  • A new chemotherapy drug is approved.
  • A new targeted therapy and a new immunotherapy are both approved for the same indication.
  • A drug’s patent is about to expire.
  • A new pharmacy opens.


Answer: A new targeted therapy and a new immunotherapy are both approved for the same indication.

25. For a PharmD student, the primary lesson from studying sequencing trials is the importance of:

  • Always choosing the therapy with the highest initial response rate.
  • Considering the entire treatment course and long-term outcomes when evaluating therapy options.
  • Memorizing the names of all clinical trials.
  • Recommending targeted therapy for all types of cancer.


Answer: Considering the entire treatment course and long-term outcomes when evaluating therapy options.

26. Dabrafenib and trametinib are examples of:

  • Checkpoint inhibitors.
  • BRAF and MEK inhibitors (targeted therapy).
  • Traditional chemotherapy.
  • Anticoagulants.


Answer: BRAF and MEK inhibitors (targeted therapy).

27. Nivolumab and ipilimumab are examples of:

  • BRAF and MEK inhibitors.
  • CTLA-4 and PD-1 inhibitors (immunotherapy).
  • Alkylating agents.
  • Reversal agents.


Answer: CTLA-4 and PD-1 inhibitors (immunotherapy).

28. A potential flaw in a sequencing trial could be:

  • A high percentage of patients in one arm not receiving the intended second-line therapy upon progression.
  • The trial being double-blinded.
  • The use of overall survival as the primary endpoint.
  • A large sample size.


Answer: A high percentage of patients in one arm not receiving the intended second-line therapy upon progression.

29. The results of a well-conducted sequencing trial can directly lead to a change in:

  • The price of the study drugs.
  • Clinical practice guidelines and the standard of care.
  • The FDA approval process.
  • The way pharmacists are licensed.


Answer: Clinical practice guidelines and the standard of care.

30. The “ECOG-ACRIN EA6134” part of the DREAMseq trial name indicates it was conducted by:

  • A single pharmaceutical company.
  • A cooperative research group.
  • The Food and Drug Administration (FDA).
  • A patient advocacy organization.


Answer: A cooperative research group.

31. The need for a specific biomarker (BRAF mutation) to enroll in the DREAMseq trial makes it a trial in the field of:

  • General internal medicine.
  • Infectious disease.
  • Precision medicine.
  • Non-sterile compounding.


Answer: Precision medicine.

32. What is a key difference between first-line PFS (PFS1) and overall survival (OS)?

  • PFS1 only measures time to progression on the first therapy, while OS incorporates the effect of all subsequent therapies.
  • OS occurs before PFS1.
  • They are identical measures.
  • PFS1 is a more reliable indicator of long-term benefit.


Answer: PFS1 only measures time to progression on the first therapy, while OS incorporates the effect of all subsequent therapies.

33. The choice of therapy sequence can be influenced by the goal of delaying:

  • The onset of a durable response.
  • The development of therapeutic resistance.
  • The need for genetic testing.
  • The use of immunotherapy.


Answer: The development of therapeutic resistance.

34. A pharmacist presenting the DREAMseq trial at a journal club would emphasize the importance of the ________ endpoint.

  • overall survival
  • progression-free survival
  • objective response rate
  • safety


Answer: overall survival

35. If a patient progresses on first-line targeted therapy, their ability to respond to second-line immunotherapy might be:

  • Enhanced.
  • Unchanged.
  • Diminished compared to an immunotherapy-naive patient.
  • Guaranteed.


Answer: Diminished compared to an immunotherapy-naive patient.

36. A key takeaway for a PharmD student from Module 5 is that establishing the best treatment sequence:

  • Is a simple decision based on drug cost.
  • Requires dedicated, large-scale randomized trials.
  • Can be determined from separate, single-agent trials.
  • Is not an important clinical question.


Answer: Requires dedicated, large-scale randomized trials.

37. The statistical design of a sequencing trial compares:

  • A single drug to a placebo.
  • Two or more different treatment strategies from initiation to second-line therapy and beyond.
  • The cost of two different drugs.
  • The safety of a drug in different patient populations.


Answer: Two or more different treatment strategies from initiation to second-line therapy and beyond.

38. The patient population in the DREAMseq trial was homogenous in terms of _______ but heterogenous in terms of _______.

  • biomarker; disease
  • disease and biomarker; treatment received
  • treatment received; disease
  • disease; biomarker


Answer: disease and biomarker; treatment received

39. Understanding sequencing trials helps pharmacists to:

  • Justify therapeutic decisions based on long-term data.
  • Compound sterile medications.
  • Perform therapeutic drug monitoring.
  • Manage pharmacy inventory.


Answer: Justify therapeutic decisions based on long-term data.

40. A primary goal of sequencing therapies in oncology is to maximize:

  • The duration of the first-line therapy.
  • The total duration of a patient’s survival.
  • The number of drugs a patient receives.
  • The cost of care.


Answer: The total duration of a patient’s survival.

41. The lecture on clinical trials in metastatic melanoma likely sets the stage for discussing:

  • The sequencing question addressed by the DREAMseq trial.
  • The use of antibiotics in cancer patients.
  • The management of chemotherapy-induced nausea.
  • The role of surgery in melanoma.


Answer: The sequencing question addressed by the DREAMseq trial.

42. Which of the following is NOT a factor when considering the optimal sequence of therapies?

  • Cumulative toxicity
  • Overall survival
  • Mechanisms of resistance
  • The color of the medication tablets


Answer: The color of the medication tablets

43. The “Team Primary Literature Presentation” for this module would likely involve a detailed critique of:

  • a basic science paper.
  • the DREAMseq trial publication.
  • a pharmacy law review.
  • a pharmacoeconomic model.


Answer: the DREAMseq trial publication.

44. If one treatment sequence leads to a higher rate of treatment discontinuation due to toxicity, this would negatively impact its value, even if efficacy is similar. This highlights the importance of considering:

  • Only overall survival.
  • The entire risk-benefit profile of the sequence.
  • The initial response rate.
  • The drug’s mechanism of action.


Answer: The entire risk-benefit profile of the sequence.

45. For a pharmacist, being able to interpret a Kaplan-Meier curve for ________ is a critical skill when evaluating a sequencing trial.

  • objective response rate
  • overall survival
  • adverse events
  • cost


Answer: overall survival

46. The central challenge that sequencing trials aim to solve is:

  • How to get a new drug approved.
  • How to best use the multiple effective drugs we already have.
  • How to find new drug targets.
  • How to manage drug shortages.


Answer: How to best use the multiple effective drugs we already have.

47. Before the DREAMseq trial, the optimal sequence for BRAF-mutant melanoma was:

  • Well-established by multiple large trials.
  • Unknown and a subject of clinical debate.
  • Known to be targeted therapy first.
  • Known to be immunotherapy first.


Answer: Unknown and a subject of clinical debate.

48. In a sequencing trial, “crossover” means that patients in the first arm who progress are offered:

  • The same therapy again.
  • A placebo.
  • The therapy that was the first-line treatment in the second arm.
  • Palliative care only.


Answer: The therapy that was the first-line treatment in the second arm.

49. The complexity of sequencing decisions underscores the need for:

  • Less communication in the healthcare team.
  • A collaborative, interprofessional approach to patient care.
  • The pharmacist to make all decisions in isolation.
  • The patient to choose their own sequence without guidance.


Answer: A collaborative, interprofessional approach to patient care.

50. An understanding of sequencing trials is essential for a pharmacist to move from simply knowing about individual drugs to understanding:

  • Long-term therapeutic strategy.
  • Drug compounding.
  • Drug chemistry.
  • Pharmacy administration.


Answer: Long-term therapeutic strategy.

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