2) @onc_ce is your ONLY source for serialized #accredited CE/#CME #tweetorials in #oncology. This program is supported by an educational grant from GSK plc and is intended for healthcare professionals. Accreditation statement and faculty disclosures at https://t.co/8oShcATWla.
— @onc_ce (@onc_ce) September 20, 2022
3b)
— @onc_ce (@onc_ce) September 20, 2022
🔓https://t.co/jSYm8TcKOZ
🔓https://t.co/kSPDdJ3K29 pic.twitter.com/W4cJpsmakJ
5) Due to the ⬆️recurrence rate, there has been a shift to molecular targeted agents (#bevacizumab & #PARPi) as #MaintenanceTherapy in order to delay progression/relapse.
— @onc_ce (@onc_ce) September 20, 2022
⬆️Therapeutic benefit
⬇️Toxicity
🔓https://t.co/ISuUT5CE2X pic.twitter.com/mLtmOTeZJg
7a) ≈50% of #OvarianCancer have defective DNA repair 2º to HRD, w/ #BRCA mutations being the most common.
— @onc_ce (@onc_ce) September 20, 2022
👉Germline BRCA (gBRCA) = 13–15%
👉Somatic BRCA = 5–10%
📍Prognostic➕predictive: BRCA mutations linked w/ ⬆️survival & ⬆️response to platinum/PARP inhibitor (#PARPi) Tx
8a) In 2014, the approval of #PARPinhibitors led to a paradigm shift in the Tx of #OvarianCancer.
— @onc_ce (@onc_ce) September 20, 2022
👉#PARPi target the DNA repair fragility of cancer cells thru:
– Impaired base excision repair (BER)
– PARP trapping
– Nonhomologous end-joining (NHEJ)
– Impaired #BRCA1 recruitment
9a) #PARPi trap PARP1 & PARP2 on DNA ➡️ PARP-DNA complexes ➡️ potentiate synergism between PARP inhibition & platinum agents
— @onc_ce (@onc_ce) September 20, 2022
👉PARP trapping potency: #talazoparib > #niraparib > #olaparib > #rucaparib > #veliparib
⚠️⬆️PARP trapping = ⬆️myelosuppression
10) If CR/PR is achieved after 1º Tx w/ surgery & platinum-based 1L chemo, @NCCN recommends #MaintenanceTherapy w/ #PARPi in certain patients w/ newly diagnosed stage II–IV disease:
— @onc_ce (@onc_ce) September 20, 2022
👉High-grade serous
👉Grade 2/3 endometrioid
👉#BRCA 1/2-mutated clear cell CA/carcinosarcoma pic.twitter.com/gx6XyZdnOD
12) Several Ph 3 RCTs ➡️significant⬆️PFS w/ use of #PARPi as #MaintenanceTherapy for pts w/ newly diagnosed @FIGOHQ stage III/IV ovarian/fallopian tube/1º peritoneal cancer after 1L chemo (regardless of #BRCA status):
— @onc_ce (@onc_ce) September 20, 2022
👉#SOLO1
👉#PAOLA1
👉#PRIMA
👉#VELIA
🔓https://t.co/cSrScHkg8q pic.twitter.com/AeiYVFCKSq
13b) #SOLO1
— @onc_ce (@onc_ce) September 20, 2022
👉Baseline characteristics were well balanced
👉Majority had no evidence of disease (NED), good ECOG PS & normal CA 125
👉Most patients had a germline #BRCA mutation pic.twitter.com/hhOVIcEJGb
13d) #SOLO1 1º safety data#Olaparib
— @onc_ce (@onc_ce) September 20, 2022
⚠️Most AEs were grade 1–2; usually managed by dose interruption/reduction; no Tx-related ☠️
⚠️Serious AEs = 21% (vs 12% w/ placebo)
⚠️Anemia – most common serious AE (7%)
⚠️Acute myeloid #leukemia (#AML) = 1% pic.twitter.com/f15NygxvtP
14b) #SOLO1 updated data
— @onc_ce (@onc_ce) September 20, 2022
📍mRFS: NR vs 15.3 mos
📍HR 0.37; 95% CI 0.27–0.52
👉63% ⬇️risk of disease relapse or death in those w/ CR
🔓https://t.co/fzI3ucPNFd https://t.co/hMKhXvL0w7 pic.twitter.com/cLLZXSrQze
14d) #SOLO1 OS data (7-yr f/u) @ #ESMO22
— @onc_ce (@onc_ce) September 20, 2022
🔗https://t.co/rWS0ctREpJ#Olaparib vs placebo
📍mOS: NR vs 75.2 mos
📍HR 0.55; 95% CI 0.40–0.76; P=0.0004
At 7 yrs…
📍Alive: 67.0% vs 46.5%
📍Alive & no 1st subsequent Tx: 45.3% vs 20.6%
✳️Despite >40% crossover in the placebo arm pic.twitter.com/SJcFtWiZCL
15a) #PAOLA1
— @onc_ce (@onc_ce) September 20, 2022
🔗🔓https://t.co/y9Fr7F0jAF
👤P: Newly diagnosed, advanced, high-grade #OvarianCancer (±#BRCA mutation) w/ a CR/PR after platinum-based Tx➕#bevacizumab (N=806)
💊I: #Olaparib for up to 2 yrs (n=537)
💊C: Placebo (n=269)
💊Both arms:➕BEV for up to 15 mos
📉O: PFS
15c) #PAOLA1
— @onc_ce (@onc_ce) September 20, 2022
👉Baseline characteristics were well balanced
👉Majority had no evidence of disease (NED)
👉30% had stage IV disease
👉30% had a #BRCA mutation
👉Almost 50% were➕HRD pic.twitter.com/bLZZ5TJhJJ
15e) #PAOLA1 efficacy data#Olaparib➕#bevacizumab vs placebo➕BEV)
— @onc_ce (@onc_ce) September 20, 2022
➕HRD (inc.➕#BRCA mutation)
📍mPFS : 37.2 vs 17.7 mos
📍HR 0.33; 95% CI 0.25–0.45
👉Greatest benefit in➕BRCA mutation patients
➕HRD (but➖BRCA mutation)
📍mPFS: 28.1 vs 16.6 mos
📍HR 0.43; 95% CI 0.28–0.66 pic.twitter.com/2ow56wDecu
15g) #PAOLA1 safety data
— @onc_ce (@onc_ce) September 20, 2022
More common w/ #olaparib➕#bevacizumab vs placebo➕BEV:
⚠️Most common AEs (overall) – fatigue, nausea, anemia
⚠️Most common serious AE – anemia (6% vs <1%)
Both arms:
⚠️Serious AEs = 31%
⚠️Fatal AEs ≈ 1%
⚠️MDS/AML/aplastic anemia/new 1º CA ≈ 1% pic.twitter.com/REwuf7xMMN
15i) #PAOLA1 important points
— @onc_ce (@onc_ce) September 20, 2022
👉Still w/ significant #olaparib benefit in➕HRD patients, even if➖#BRCA mutation (due to addition of OLA❓OLA➕#bevacizumab synergism❓)
👉In➕HRD patients on 1st-line BEV, best to add olaparib (significant ⬆️OS)
👉Addition of OLA did not ⬆️AEs
16b) #PRIMA
— @onc_ce (@onc_ce) September 20, 2022
👉Baseline characteristics were well balanced
👉Included patients at ⬆️risk for PD:
– Stage III w/ R+ 1º resection (23.1%)
– Post-NACT (66.7%)
– PR post-1L chemo (30.5%)
– Stage IV (35%)
👉➕HRD = 50.9% (➕#BRCA mutation = 59.8%) pic.twitter.com/kV4ELUt1Ot
16d) #PRIMA safety data#Niraparib
— @onc_ce (@onc_ce) September 20, 2022
⚠️Most common AEs (grade ≥3) – anemia (31%), thrombocytopenia (28.7%), neutropenia (12.8%)
⚠️Dose reduction in 70.9% & Tx discontinuation in 12% (due to myelosuppression)
⚠️No Tx-related ☠️
⚠️MDS = 1 case pic.twitter.com/zdwZt5Ok9F
17a) #VELIA
— @onc_ce (@onc_ce) September 20, 2022
🔗🔓https://t.co/lKfKHf1dl2
👤P: Tx-naive, advanced, high-grade #OvarianCancer (±#BRCA mutation) (N=1140)
💊I1: Chemo➕#veliparib (VEL) ➡️ placebo (PBO) maintenance (n=375)
💊I2: Chemo➕VEL ➡️ VEL maintenance (n=383)
💊C: Chemo➕PBO ➡️ PBO maintenance (n=382)
📉O: PFS
17c) #VELIA efficacy data (median f/u = 28 mos)#Veliparib throughout vs control
— @onc_ce (@onc_ce) September 20, 2022
ITT
📍mPFS: 23.5 vs 17.3 mos
📍HR 0.68; 95% CI 0.56–0.83*
➕BRCA mutation
📍mPFS: 34.7 vs 22 mos
📍HR 0.44; 95% CI 0.28–0.68*
➕HRD
📍mPFS: 31.9 vs 20.5 mos
📍HR 0.57; 95% CI 0.43–0.76*
*P<0.001 pic.twitter.com/9zmJRr2h2w
17e) #VELIA important points
— @onc_ce (@onc_ce) September 20, 2022
👉⬆️PFS w/ induction #veliparib (VEL) ➡️ maintenance VEL vs chemo alone (esp. in➕HRD/➕#BRCA mutation patients)
👉Induction VEL w/o maintenance VEL benefit❓
👉⬇️Toxicity w/ VEL monotherapy vs other #PARPi (indirect comparison)
⚠️Not FDA-approved
19) Mark your best response and return tomorrow for the correct answer and more #accredited education!
— @onc_ce (@onc_ce) September 20, 2022
👏@HemOncFellows @pedroramirezMD @agz_eriksson @SGO_org @pedroramirezMD @IJGConline @IJGCfellows @ESGO_society @AinhoaMada @VukovicPetra @ShannonWestin @TeamOvary_MSK
21) Welcome back! I am @DrMeredithGT, we are talking about #PARPi in maintenance treatment of patients with advanced #OvarianCancer, and YOU are earning 🆓 CE/#CME! Thank you for joining us on your ONLY source for #accredited #oncology education delivered entirely on Twitter!
— @onc_ce (@onc_ce) September 21, 2022
22b) #PARPi as frontline #MaintenanceTherapy in #OvarianCancer
— @onc_ce (@onc_ce) September 21, 2022
➕HRD
📍HR 0.39; 95% CI 0.29–0.53
👉Clinically significant ⬆️PFS
➖HRD
📍HR 0.83; 95% CI 0.67–1.03
👉No clear difference pic.twitter.com/jq4KEXYR4Y
23) 👀BONUS: Look at this simplified algorithm summarizing the frontline #MaintenanceTherapy options for advanced stage, high-grade #OvarianCancer following response to 1L platinum-based chemo
— @onc_ce (@onc_ce) September 21, 2022
🔗🔓https://t.co/OohWg2MTKJ pic.twitter.com/cru2UIxM2c
25) Several RCTs have shown a significant ⬆️PFS w/ the use of #PARPi as #MaintenanceTherapy for patients w/ platinum-sensitive recurrent #OvarianCancer (regardless of #BRCA mutation status):
— @onc_ce (@onc_ce) September 21, 2022
👉#Study19
👉#SOLO2
👉#NOVA
👉#ARIEL3
See 🔓https://t.co/cSrScHkNXY pic.twitter.com/YdbGZ8JcFI
26b) #Study19
— @onc_ce (@onc_ce) September 21, 2022
👉Baseline characteristics were well balanced
👉➕#BRCA mutation = 51% pic.twitter.com/13tEI005XC
26d) #Study19 safety data#Olaparib (OLA) vs placebo
— @onc_ce (@onc_ce) September 21, 2022
⚠️Most common AEs w/ OLA – nausea, fatigue, vomiting, diarrhea, anemia
⚠️Tx discontinuation = 7 vs 2 patients
⚠️Serious AEs = 18% vs 9%
⚠️Most common serious AE – small intestinal obstruction (1% vs 2%) pic.twitter.com/jRrfmDOsgg
26f) #Study19 important points
— @onc_ce (@onc_ce) September 21, 2022
👉Numerical OS advantage w/ #olaparib (OLA) vs placebo regardless of #BRCA mutation status (➕>➖), but the predefined threshold for statistical significance was not met
👉≈10% continued OLA for ≥6 yrs
27b) #SOLO2
— @onc_ce (@onc_ce) September 21, 2022
👉Baseline characteristics were well balanced
👉Most patients had a germline #BRCA mutation (97%)
👉Prior #bevacizumab exposure (#olaparib vs placebo): 17% vs 20%
👉38% of patients in the placebo group received subsequent #PARPi Tx pic.twitter.com/iEQkqjQw8U
27d) #SOLO2 final OS analysis (median f/u = 65 mos)
— @onc_ce (@onc_ce) September 21, 2022
🔗https://t.co/sYlLTs74Us#Olaparib vs placebo (PBO)
📍mOS: 51.7 vs 38.8 mos
📍HR 0.74; 95% CI 0.54–1.00; P=0.054
Adjusted for subsequent #PARPi Tx in the PBO arm
📍mOS: 51.7 vs 35.4 mos
📍HR 0.56; 95% CI 0.35–0.97 pic.twitter.com/SZTY5qdIYd
27f) #SOLO2 important points
— @onc_ce (@onc_ce) September 21, 2022
👉OS benefit of 12.9 mos w/ #olaparib (OLA) in patients w/ recurrent #OvarianCancer (➕#BRCA mutation)
👉Statistical significance not reached (⬆️crossover), but still clinically meaningful
👉Earlier use of OLA ➡️ greater benefit
28b) #NOVA
— @onc_ce (@onc_ce) September 21, 2022
👉Baseline characteristics were well balanced
👉➕Germline #BRCA mutation = 37%
👉Majority had stage III–V #OvarianCancer
👉Received ≥3 lines of chemo (➕gBRCA mutation vs➖gBRCA mutation): 50% vs 33%
👉Included patients w/ prior #bevacizumab use pic.twitter.com/dZ2TptCgtc
28d) #NOVA 1º safety data#Niraparib
— @onc_ce (@onc_ce) September 21, 2022
⚠️Most common grade 3–4 AEs – thrombocytopenia (33.8%), anemia (25.3%), neutropenia (19.6%) ➡️ managed w/ dose modification
⚠️Tx discontinuation = 14.7% (vs 2.2% w/ placebo)
⚠️No Tx-related ☠️
⚠️MDS = 5 cases (1.4%) pic.twitter.com/acywvwDTf0
— @onc_ce (@onc_ce) September 21, 2022
28g) #NOVA updated safety data#Niraparib
— @onc_ce (@onc_ce) September 21, 2022
⚠️⬇️Grade ≥3 hematologic AEs (thrombocytopenia, anemia, neutropenia) after 1 yr
⚠️MDS/AML = 13 cases (3.5%) pic.twitter.com/ptrgt0gnu2
29a) #ARIEL3
— @onc_ce (@onc_ce) September 21, 2022
🔗https://t.co/jAMWXPFs2I
👤P: Patients w/ platinum-sensitive, recurrent high-grade #OvarianCancer (±BRCA mutation) w/ a CR/PR after ≥2 platinum-based chemo regimens (N=564)
💊I: #Rucaparib 600mg BID (n=375)
💊C: Placebo (n=189)
📉O: PFS pic.twitter.com/1MOPS6y64e
28c) #ARIEL3 1º efficacy data#Rucaparib vs placebo
— @onc_ce (@onc_ce) September 21, 2022
➕BRCA mutation
📍mPFS: 16.6 vs 5.4 mos
📍HR 0.23; 95% CI 0.16–0.34*
➕HRD
📍mPFS: 13.6 vs 5.4 mos
📍HR 0.32; 95% CI 0.24–0.42*
ITT
📍mPFS: 10.8 vs 5.4 mos
📍HR 0.36; 95% CI 0.30–0.45*
*P<0.0001 pic.twitter.com/UH8XPVu4jc
28e) #ARIEL3 updated efficacy data
— @onc_ce (@onc_ce) September 21, 2022
🔗https://t.co/UBj4QwJqQd#Rucaparib vs placebo
➕BRCA mutation
📍mPFS2: 26.8 vs 18.4 mos
📍HR 0.56; 95% CI 0.38–0.83
➕HRD
📍mPFS2: 25.3 vs 18.4 mos
📍HR 0.66; 95% CI 0.49–0.87
ITT
📍mPFS2: 21 vs 16.5 mos
📍HR 0.66; 95% CI 0.53–0.82 pic.twitter.com/MgM5Pi7LhB
28g) #ARIEL3 important points
— @onc_ce (@onc_ce) September 21, 2022
👉#Rucaparib #MaintenanceTherapy in recurrent #OvarianCancer led to ⬆️PFS & delayed the need for subsequent Tx regardless of HRD status & other clinical prognostic factors
👉Tolerable safety profile w/ ⬇️incidence of Tx discontinuation due to AEs
29b) @cochranecollab #metaanalysis (PFS comparison)#PARPi vs placebo
— @onc_ce (@onc_ce) September 21, 2022
📍➕BRCA mutation: HR 0.27; 95% CI 0.20–0.36
📍➖BRCA mutation: HR 0.50; 95% CI 0.39–0.63
📍➕HRD: HR 0.35; 95% CI 0.27–0.46
📍➖HRD: HR 0.58; 95% CI 0.36–0.93
👉Greater PFS benefit in➕BRCA &➕HRD patients pic.twitter.com/M1HGUEljY8
30) 👀Check out this #RealWorld study on #PARPi Tx in #OvarianCancer
— @onc_ce (@onc_ce) September 21, 2022
🔗https://t.co/yMdJFVD3VL
📍#Niraparib (NIR) vs #olaparib (OLA): OR 3.36; 95% CI 2.00–5.65
📍NIR vs #rucaparib (RUC): OR 2.09; 95% CI 1.10–3.95
📍RUC vs OLA: OR 1.61; 95% CI 0.93–2.79 (no significant difference) pic.twitter.com/Bypk7AWKSg
32) Welcome back to the conclusion of our very comprehensive review of #PARP Inhibitors for the Maintenance Treatment of Patients with Advanced #OvarianCancer. I am @DrMeredithGT 🇵🇭, IDEA mentee of @drdonsdizon, and you are only a few 🖱️clicks away from ONE HOUR 🆓CE/#CME!
— @onc_ce (@onc_ce) September 22, 2022
34) That’s ☝️the summary as well from 🔓https://t.co/2GmV1p7BnC. And here's 👇@NCCN summary of #MaintenanceTherapy options for #OvarianCancer (https://t.co/dZLwboULUw)
— @onc_ce (@onc_ce) September 22, 2022
🟩Frontline: #Olaparib±#bevacizumab, #niraparib
🟥Recurrence: Niraparib, olaparib, #rucaparib pic.twitter.com/jDwL2PrZIC
35b) Per https://t.co/dZLwboVjK4, your best option is #4, #niraparib alone: pic.twitter.com/bkrTRg8xox
— @onc_ce (@onc_ce) September 22, 2022
36b) Per https://t.co/dZLwboULUw, your best choice is 2, #bevacizumab + #olaparib: pic.twitter.com/LlDj08c3jg
— @onc_ce (@onc_ce) September 22, 2022
37b) Per https://t.co/dZLwboVjK4, your best choice is 3, #olaparib, #rucaparib or #niraparib alone: pic.twitter.com/MeNGhDO4dg
— @onc_ce (@onc_ce) September 22, 2022
38) WHEW!! You did it! You just earned a full hour CE/#CME credit. You can claim your certificate right now at https://t.co/w1DoPIF1wG and please follow us for more #accredited #tweetorials by expert authors! I am @DrMeredithGT. THANK YOU for joining!
— @onc_ce (@onc_ce) September 22, 2022