First-line rucaparib maintenance therapy after platinum-based chemotherapy improved the progression-free survival (PFS) of patients with stage III–IV ovarian cancer in the ATHENA-MONO trial. Further tumour reductions were reported following treatment with rucaparib.
The efficacy of the PARP inhibitor rucaparib has been established in patients with platinum-sensitive recurrent ovarian cancer . Also, PARP inhibitors have delivered PFS benefits as first-line maintenance treatment . However, the optimal first-line maintenance strategy for patients with advanced ovarian cancer is still unclear.
The phase 3 ATHENA trial (NCT03522246) randomised patients with FIGO stage III or IV ovarian cancer, who responded to first-line platinum-based doublet chemotherapy, 4:4:1:1 to rucaparib plus nivolumab (arm A), rucaparib plus placebo (arm B), placebo plus nivolumab (arm C), and placebo plus placebo (arm D). Prof. Bradley Monk (University of Arizona, AZ, USA) discussed the results of the ATHENA-MONO trial, comparing arm B (n=427) with arm D (n=111) . Investigator-assessed PFS was the primary outcome of the trial.
Rucaparib was associated with an improvement in the median PFS of patients with homologous recombination deficiency-positive tumours (28.7 vs 11.3 months; HR 0.47; P=0.0004) and in the median PFS of the intention-to-treat population (20.2 vs 9.2 months; HR 0.52; P<0.0001). The PFS per blinded, independent, central review demonstrated similar results. Furthermore, the PFS benefit of rucaparib was consistent among BRCA-mutated (HR 0.40), BRCA wildtype/loss of heterozygosity high (HR 0.58), and homologous recombination deficiency-negative patients (HR 0.65). Prof. Monk pointed out that patients with the highest risk (residual disease, stage IV, abnormal CA-125 levels) appeared to benefit more from treatment with rucaparib.
In total, 60.5% of the patients on rucaparib experienced grade ≥3 adverse events (AEs) compared with 22.7% of the patients in the placebo arm. Most treatment-emergent AEs in the active arm were of gastrointestinal origin or marrow-related, and could be mitigated with dose reductions or dose interruptions. The discontinuation rate was 11.8% in patients receiving rucaparib.
Rucaparib showed to be effective as first-line maintenance monotherapy with significant benefits over placebo in the intention-to-treat and homologous recombination deficiency patients.
- Coleman RL, et al. Lancet. 2017;390:1949‒1961.
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- Monk BJ, et al. ATHENA–MONO (GOG-3020/ENGOT-ov45): A randomized, double-blind, phase 3 trial evaluatingrucaparibmonotherapy versus placebo as maintenance treatment following response to first-line platinum-basedchemotherapy in ovariancancer. LBA5500, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.
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Table of Contents: ASCO 2022
Letter from the Editor
ASCO 2022 Highlights Podcast
Sacituzumab govitecan meets primary endpoint
Shaky OS results of palbociclib in ER-positive/HER2-negative breast cancer
Practice-changing results of T-DXd in HER2-low breast cancer
SET2,3 to inform on chemotherapy decisions in ER-positive breast cancer
Metastasis-directed therapy fails in oligometastatic breast cancer
Analysis by residual cancer burden further clarifies effect of pembrolizumab
Contribution of metastatic therapies on mortality reduction in breast cancer
Radiotherapy may be omitted in breast cancer patients
Promising data for ribociclib after progression on ET plus CDK4/6 inhibitors in HR-positive/HER2-negative metastatic breast cancer
7-gene biosignature: Benefits of endocrine therapy and radiotherapy in breast cancer risk groups
Additional tiragolumab does not help patients with untreated small cell lung cancer
Success for serplulimab plus chemotherapy in small cell lung cancer
Adagrasib safe and clinically active in non-small cell lung cancer
Long-term benefits of combined immunotherapy over chemotherapy in non-small cell lung cancer
Effect of KRAS mutations and PD-L1 expression on therapy response in non-small cell lung cancer
First results on distant metastasis-free survival in stage II melanoma
Higher response rates for concurrent triple therapy versus sequential therapy in melanoma
Exploratory treatment options fail in ccRCC
Adjuvant everolimus did not benefit high-risk renal cell carcinoma
Cabozantinib fails as first-line maintenance therapy in urothelial cancer
177Lu-PSMA-617 is a valid treatment option for PSMA-positive mCRPC
Enzalutamide performs well in metastatic hormone-sensitive prostate cancer
Autologous stem cell transplantation plus RVd improves PFS in multiple myeloma
Novel first-line treatment option for mantle cell lymphoma
Promising results for novel CAR-T therapy in relapsed/refractory multiple myeloma
Panitumumab beats bevacizumab in RAS wildtype left-sided metastatic colorectal cancer
Spectacular results for dostarlimab in mismatch repair deficient rectal cancer
Triplet chemotherapy beats doublet chemotherapy in colorectal cancer liver metastases
To resect or not to resect primary tumours in stage IV colon cancer?
Novel treatment option for KRAS wildtype pancreatic cancer
Primary results of rucaparib in ovarian cancer
Trabectedin not superior to chemotherapy in recurrent epithelial ovarian cancer
Encouraging results of relacorilant in ovarian cancer
Bacterial decolonisation effective against radiation dermatitis
New standard-of-care for cisplatin-ineligible locally advanced head and neck squamous cell carcinoma
Ifosfamide is likely to be the go-to therapy in recurrent Ewing sarcoma
Dabrafenib plus trametinib candidates for standard-of-care in BRAF V600-mutated paediatric low-grade glioma