UICMEW | Pre-Test

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1. Which of the following statements about the FLAURA2 study is true?

Osimertinib and chemotherapy are FDA-approved in the 1L setting of mNSCLC with an EGFR ex19 del or ex21 L858R mutation

Osimertinib and chemotherapy showed similar toxicity profile as Osimertinib alone

Osimertinib and chemotherapy showed an OS benefit over Osimertinib alone

Osimertinib and chemotherapy showed a PFS benefit over Osimertinib alone

1. MBC: In the SONIA trial, patients were randomly assigned to receive AI therapy versus AI therapy plus a CDK4/6 inhibitor as initial therapy for HR+, HER2- metastatic disease followed by switch to Fulvestrant plus CDK4/6 inhibitor versus Fulvestrant alone at initial progression, respectively. Which of the following was not observed?

There was no overall survival difference between arms

Progression-free survival-1 (PFS-1) was better for combination treatment over ET alone but statistically equivalent at PFS-2

No new major safety signals were observed

The distribution of CDK4/6 inhibitors used was similar for all three commercially available agents

Patients on upfront combination therapy had more days spent experiencing greater overall toxicities than patients who received combination therapy in the second line.

2. 80% of patients with high grade ovarian cancer will eventually experience recurrence. Unfortunately PFS and ORR have been shown to decreased with each subsequent line of therapy. In the last few years there have been advances in biomarker-based drug development for upfront maintenance therapy and for recurrent ovarian cancer. Which of the statements below is correct?

PARP inhibitor Olaparib has been shown to have efficacy as maintenance therapy in ovarian cancer patients in the recurrent platinum resistant setting as well as in the upfront setting irrespective of HRD status

PARP inhibitor Olaparib can be used as maintenance therapy following primary chemotherapy or after recurrence but dosing needs to be adjusted for weight <77kg and platelets <150,000/mm3

Parp inhibitor Niraparib showed clinically significant improvement in PFS over 3.5 yrs of follow up in patients with recurrent but not newly diagnosed advanced ovarian cancer

Mirvetuximab demonstrated benefit over single agent chemotherapy in the platinum resistant setting irrespective to whether or not they had received prior bevacizumab or Parp inhibitor

Mirvetuximab is an antibody-drug conjugate against tissue factor and has unique adverse effects that includes conjunctivitis

3. Genetics: Which of the following statements is true regarding contralateral breast cancer risk (CBC) among carriers of pathogenic variants in hereditary breast cancer genes in the CARRIERS study?

The hormone receptor status of the initial primary breast tumor does not effect the risk of CBC for any hereditary breast cancer syndrome.

For the moderate penetrance ATM gene, the risk of CBC is similar to the risk for non-carriers of pathogenic variants.

Among all women with hereditary breast cancer syndromes, menopausal status at the time of the initial breast cancer diagnosis effects CBC risk only for BRCA1 and BRCA2 carriers.

CBC risk is high enough to qualify for MRI screening as an adjunct to mammograph for premenopausal CHEK2 carriers with ER-negative tumors and premenopausal PALB2 carriers with ER-positive tumors.

Both B and D are true

4. The KEYNOTE 522 trial evaluated the addition of pembrolizumab vs placebo to preoperative systemic chemotherapy for early stage triple negative breast cancer with immunotherapy. Which of the following was not a feature or finding of the study:

Both the co-primary of pathologic complete response rates and event free survival were statistically met in favor of the addition of pembrolizumab

The study was positive favoring pembrolizumab efficacy over placebo and only at the expense of an increase by 5% of treatment related adverse events between arms

Patients noted to have a pathologic complete response at surgery were permitted to discontinue pembrolizumab or placebo

Treatment relevant adverse events attributable to pembrolizumab were observed primarily in the neoadjuvant phase of treatment

Which of the following is true regarding revumenib for treatment of r/r KMT2Ar AML?

A. Heavily pretreated patients with r/r KMT2Ar AML demonstrated promising overall response rates in the AUGMENT-101 Phase 2 study.

B. Most patients achieving CR or CRh also demonstrated MRD negativity.

C. The most common adverse events included nausea, differentiation syndrome, and QTc prolongation.

D. All of the above.

E. I'm not sure.

Mr. R is a 79M with PMHx significant for stage IIIB DLBCL s/p R-CHOP x 6 cycles (finished therapy 3 years ago) who was recently found to have recurrent disease. He is deemed not to be a transplant candidate but would still favor definitive therapy if possible. He presents to clinic to further discuss possible definitive options for his R/R DLBCL. Based on current FDA-recommendations, what treatment regimen would you most likely recommend for your patient?

Common side effects of menin inhibitors such as ruvemenib include:

A. Interaction with azoles

B. Interaction with azoles, QTc prolongation

C. Interaction with azoles, QTc prolongation, differentiation syndrome

D. Interaction with azoles, QTc prolongation, differentiation syndrome

E. Interaction with azoles, QTc prolongation, differentiation syndrome, and positive cytogenetics despite blast disappearance

63-year-old man with triple refractory Multiple Myeloma is on cycle #6 of GPRC5D-bispecific antibody (Talquetamab) at 0.8 mg/kg every 2 weeks with a complete response per IMMWG criteria. Patient developed an erythematous rash covering 50% of BSA. Skin biopsy shows interface dermatitis. Rash has had a partial response to systemic corticosteroids. An option in the management of this complication would be:

A. Discontinue Talquetamab and start Teclistamab

B. Talquetamab dose reduction to 0.8 mg/kg every 4 weeks

C. Hydrocortisone cream 1%

D. Patch testing for allergens

E. Check tryptase and IgE levels.