Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy

Abstract

BACKGROUND: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. METHODS: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79% maturity) data, from the last data cut-off (9 May 2016). RESULTS: Thirty-two patients (24%) received maintenance olaparib for over 2 years; 15 (11%) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6%). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95% confidence interval 0.55-0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met. CONCLUSIONS: Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented longterm benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients.

Targeted therapies in gynaecological cancers

“…The median progression‐free survival (PFS) from randomisation ranges from 11.2 to 21 months for BRCA1/2 mutant populations and from 7.4 to 10.8 months for BRCA1/2 wild‐type/all‐comer populations . To date, no improvement has been observed in overall survival (OS), but with long‐term follow up in study 19, 11% of patients remained on olaparib for more than 6 years without evidence of cancer progression . Olaparib and rucaparib have additional licences as monotherapy for recurrent BRCA1/2 mutant ovarian cancer .…”

“…4,[22][23][24][25] To date, no improvement has been observed in overall survival (OS), but with long-term follow up in study 19, 11% of patients remained on olaparib for more than 6 years without evidence of cancer progression. 26 Olaparib and rucaparib have additional licences as monotherapy for recurrent BRCA1/2 mutant ovarian cancer. 17,18,20,21 Overall response rates (ORR) of between 31% to 41% in BRCA1/2 mutation carriers and up to 24% in BRCA wild-type patients have been demonstrated with olaparib monotherapy, 27,28 and up to 53.8% with rucaparib monotherapy in BRCA1/2-mutated patients.…”

Practical aspects of treating relapsed BRCA-associated ovarian cancer

“…Отсутствие различий могло быть обусловлено тем фактом, что значительное количество пациенток из группы плацебо (23%) получили терапию олапарибом после прогрессирования заболевания [18]. Отметим, что 18 (13%) пациенток из группы олапариба получали терапию препаратом в течение ≥5 лет, у 11 пациенток была выявлена мутация в генах BRCA1/2; для сравнения: только 1 пациентка из группы плацебо получала терапию в течение аналогичного периода времени [19].…”

“…Интересным аспектом развития токсичности, ассоциированной с применением олапариба, является то, что наибольшее количество эпизодов развития нежелательных явлений приходилось на первые 6 месяцев терапии препаратом. По этой причине необходим тщательный мониторинг за состоянием пациенток в первые месяцы применения препарата, включая регулярный контроль показателей периферической крови [19].…”

Changes in DNA Damage Response Markers with Treatment in Advanced Ovarian Cancer

“…As such, both PAR and PARP-1 expression provide a read-out for BER activity. In addition, PARPi are becoming standard of care as maintenance therapy for both first line BRCA1/2-mutated OC and platinum-sensitive relapsed high-grade OC regardless of the BRCA status [19][20][21][22]. Therefore, greater knowledge regarding the expression of the target, PARP-1, in OC throughout the disease course may become critical.…”