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PARP inhibitor monotherapy prolonged disease control in a case of recurrent epithelial ovarian cancer without BRCA mutation

Prof. Roger Ngan
Department of Clinical
Oncology
The University of Hong Kong
03 Apr 2020

History, presentation and management

This patient presented to the clinic at the second recurrence of the dis­ease with extensive spread of cancer within the abdomen. Since her dis­ease progressed 10 months after the last course of platinum-based che­motherapy, she was still considered platinum-sensitive.1,2 She received cytoreductive surgery and hyperther­mic intraperitoneal chemotherapy, and in accordance with the Euro­pean Society for Medical Oncology (ESMO)-European Society of Gynae­cological Oncology (ESGO) recom­mendations,1 she was given third-line platinum-based chemotherapy. Because the patient responded well to the platinum rechallenge, olaparib maintenance therapy was chosen.1 (Figure)

062mo1

Discussion

Olaparib is a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor indicated for maintenance treatment in patients with recur­rent epithelial ovarian cancer who are in complete or partial response to platinum-based chemotherapy.3* In the phase III SOLO2 study in 295 patients with a BRCA1/2 mutation, investigator-assessed median progression-free sur­vival (PFS) was significantly longer with olaparib tablet 300 mg BID than placebo (19.1 months vs 5.5 months; hazard ratio [HR], 0.30; 95 percent confidence interval [CI], 0.22 to 0.41; p<0.0001).4

While evidence suggests that PARP inhibitors provide the greatest benefits in patients with BRCA mutation,1 olapa­rib has demonstrated survival benefits in those without the mutation as well.5 The phase II study 19 included 265 patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer with or with­out BRCA1/2 germline mutations.5 Medi­an PFS was significantly longer in those receiving olaparib capsule 400 mg BID than those receiving placebo (8.4 months vs 4.8 months; HR, 0.35; 95 percent CI, 0.25 to 0.49; p<0.001).5 Subgroup anal­yses also favoured olaparib regardless of BRCA status (with mutation: HR, 0.18; 95 percent CI, 0.10 to 0.31; p<0.0001) (without mutation: HR, 0.54; 95 percent CI, 0.34 to 0.85; p=0.0075).5,6

Olaparib was well tolerated in both SOLO2 and study 19.4,5 Fewer than 50 percent of patients receiving olaparib required dose interruption or reduction due to adverse events (AEs); the most common grade 3 AEs were anaemia, fatigue and neutropenia.4,5 Olapar­ib is now available in tablet form, which offers a reduced pill burden compared with the original 50 mg capsule formu­lation.7 It should be mentioned that the two formulations are not bioequivalent and the doses are not interchangeable: expert opinions suggest that 400 mg capsules BID may be switched to 300 mg tablet BID; and 200 mg capsules BID to 250 mg tablet BID.3,7

The present case echoes the find­ings from the clinical trials in that olapa­rib maintenance therapy prolongs disease control in a patient with recur­rent epithelial ovarian cancer. The fact that the patient has no BRCA mutation was particularly encouraging, highlight­ing the utility of olaparib irrespective of BRCA status. Most importantly, the patient remained well after 12 months of treatment and was able to maintain a high-quality, active lifestyle.


 

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Most Read Articles
14 Feb 2020
The phase III CASTOR and POLLUX studies previously demonstrated benefit of daratumumab plus bortezomib and dexamethasone (DVd) or lenalidomide and dexamethasone (DRd) vs standard-of-care (SoC) Vd or Rd regimen in relapsed or refractory multiple myeloma (R/R MM). The latest efficacy and safety results after 4 years of follow-up from CASTOR and POLLUX were presented at the American Society of Hematology (ASH) 61st Meeting & Exposition 2019 held in Orlando, Florida, US.  
Dr. Michael Tsz-Yeung Kam, 3 days ago

Third-generation EGFR tyrosine kinase inhibitors (TKIs) targeting the EGFRT790M mutation, such as osimertinib, have brought significant improvements to the management of EGFR-positive non-small-cell lung cancer (NSCLC). However, optimization of EGFRT790M mutation testing remains challenging in clinics. At a symposium organized by the Hong Kong Cancer Therapy Society, Dr Michael Tsz-Yeung Kam, Specialist in Clinical Oncology in Hong Kong, discussed real-world challenges in EGFRT790M testing and the current workflow at his centre.

Christina Lau, 03 Oct 2019

Pembrolizumab, used in both neoadjuvant and adjuvant settings, significantly improves pathological complete response (pCR) in patients with early triple-negative breast cancer (TNBC), according to late-breaking results of the phase III KEYNOTE-522 trial presented at the European Society for Medical Oncology (ESMO) Congress 2019.

Dr. Jeff P. Sharman, 13 Feb 2020
Acalabrutinib, used in combination with obinutuzumab or as monotherapy, improved progression-free survival (PFS) by 80–90 percent vs chlorambucil with obinutuzumab in patients with previously untreated chronic lymphocytic leukaemia (CLL) in the phase III ELEVATE TN trial. The results, presented at the American Society of Haematology 61st Annual Meeting & Exposition (ASH 2019) by Dr Jeff P. Sharman of the Willamette Valley Cancer Institute and Research Center in Eugene, Oregon, US, demonstrated consistent PFS benefit across patient subgroups as well as tolerability of acalabrutinib therapy.