Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety
Bibliographic record
Abstract
Objective To report results from an integrated efficacy and safety analysis supporting the European Commission9s approval of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy treatment for relapsed, platinum-sensitive, BRCA-mutated ovarian cancer. Methods Efficacy was analyzed in platinum-sensitive patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who had high-grade serous or endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer and a deleterious BRCA1 or BRCA2 mutation and received two or more prior chemotherapies (including two or more platinum-based therapies). The primary end point was investigator-assessed, confirmed objective response rate (visit cut-off: April 10, 2017). Safety was analyzed in patients with ovarian cancer, regardless of BRCA mutation status or lines of prior chemotherapies, who received at least one dose of rucaparib 600 mg in either study (visit cut-off: December 31, 2017). Results In the integrated platinum-sensitive efficacy population (n=79), objective response rate was 64.6% (95% CI, 53.0 to 75.0); 10.1% (8/79) of patients had a complete response and 54.4% (43/79) had a partial response. Median duration of response was 294 days (95% CI, 224 to 393). In the integrated safety population (n=565), the most common any-grade treatment-emergent adverse events were nausea (77.7%, 439/565), asthenia/fatigue (74.7%, 422/565), vomiting (45.8%, 259/565), and hemoglobin decreased (44.2%, 250/565). Treatment-emergent adverse events led to treatment interruption, dose reduction, or discontinuation in 60.2% (340/565), 46.0% (260/565), and 16.8% (95/565) of patients. Conclusions In patients with platinum-sensitive, BRCA-mutated ovarian cancer, rucaparib demonstrated antitumor activity and is the first and currently the only poly(ADP-ribose) polymerase inhibitor approved by the European Commission as treatment for this population. The safety analysis used a more recent visit cut-off date and larger population than previously published, was consistent with prior reports, and was the basis for the treatment-indication safety population in rucaparib’s recently updated European Union label.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".