Chemo/Immunotherapy

Question 1

Olaparib

Answer 1

FDA approved as maintenance therapy in patients with BRCA mutated platinum sensitive recurrent ovarian cancer & response to last platinum chemo.

• *this approval was based on Study 19 (phase 2) results, which were subsequently confirmed by SOLO1 trial (phase 3 multicenter)
• *SOLO1 showed 34 month median PFS
• inhibits PARP 1/2/3
• a MITO study showed that Olaparib given after 3-4 prior lines of chemo had a shorter PFS….give at first recurrence?

–approved for 2 years maintenance tx

-lower rates of G3 thrombocytopenia compared to niraparib

Question 2

What are the 3 FDA approved indications for Pembrolizumab?

Answer 2

1. Advanced/recurrence cervical cancer that has a CPS of >/ 1
2. MSI-High endometrial cancer
3. MSI-stable endometrial cancer

Question 3

Bevacizumab

Answer 3

FDA approved in 2018 for EOC based on median PFS 6.2 months in GOG 218 in combo w/ chemo & as maintenance

-OS benefit most significant w/ higher stage & ascites

Question 4

Niraparib

Answer 4

Approved for all patients in APR2020 as maintenance; 5.6 mo mPFS, 11.5 mo if homologous recombination deficient tumors (PRIMA trial)

• can give as maintenance up to 3 years
• in NOVA study, starting dose of 300mg associated with high rates of dose reductions. Retrospective analysis identified body weight of 77kg or baseline platelet count <150k as predictive of thrombocytopenia reductions. **No PFS difference observed with 200mg or 100mg dose vs 300mg dose. Recommended starting dose w/ these risk factors = 200mg

Question 5

Olap + Bev

Answer 5

FDA approved this combo May 2020 for HRD +/BRCAwt based on PAOLA trial; 16 mo mPFS w/ combo vs Bev alone

-FDA approved. Ompaniom diagnostic test if not BRCAm = myChoice HRD test

Question 6

1. Maintenance for BRCAm w/ EOC
2. Maintenance for BRCAwt / HRD + (myChoice HRD companion test FDA approved)
3. Maintenance for HRD (-) / homologous repair proficient

Answer 6

1. Olap, based on SOLO1
2. Olap + Bev OR Niraparib (PRIMA trial)
3. Bev (GOG218- 6 mo PFS) or Niraparib

Question 7

PARPi’s

Answer 7

Prevent repair single stranded DNA breaks via base excision repair pathway –> result in double stranded breaks

Question 8

PARPi approved for primary maintenance in advanced ovarian ca

Answer 8

Olap (SOLO 1, BRCAm)
Olap + Bev (PAOLA 1)
Niraparib (PRIMA, BRCAm)

Question 9

Pazopanib

Answer 9

Oral anti-angiogenic therapy, small molecule inhibitor of VEGF 1/2/3, platelet derived growth factor receptor, and C-Kit tyrosine kinases.

-Paz+Gem in platinum resistant EOC demonstrates PFS 3mos vs gem alone, no OS (phase II study)