Abstract NT-101: QUADRA: A PHASE 2, OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE SINGLE-AGENT NIRAPARIB TREATMENT IN PATIENTS WITH RELAPSED OVARIAN CANCER (ROC) WHO HAVE RECEIVED ≥3 PRIOR CHEMOTHERAPY REGIMENS
Bibliographic record
Abstract
Abstract BACKGROUND: Patients with ROC have limited treatment options in later lines of therapy, as many become platinum-resistant or -ineligible. Poly(ADP-ribose) polymerase inhibitor (PARPi) treatment is one option, however these agents are currently not approved for BRCAwt patients in the treatment setting. Niraparib, a PARPi, has demonstrated increased progression-free survival vs placebo as maintenance therapy for platinum-responsive ROC. Niraparib was effective regardless of BRCAmut or homologous recombination deficiency (HRD) status, although an increased treatment effect was observed in the HRDpos population. QUADRA (NCT02354586) evaluated niraparib treatment in heavily pretreated ROC patients, regardless of BRCAmut or HRD status, platinum sensitivity, or prior PARPi use. METHODS: Eligible patients had grade 2-3 serous ROC, ≥3 prior chemotherapy lines, and measurable disease. Patients were evaluated for BRCAmut and HRD status (MyChoice HRD Test). Patients received niraparib 300 mg once daily until progression; dose could be lowered to 200 mg or 100 mg due to treatment-emergent adverse events (TEAEs). The primary endpoint was objective response rate (ORR) per RECIST v1.1 in patients treated in 4th or 5th line who were HRDpos, platinum sensitive, and PARPi naïve. RESULTS: 463 patients were treated. Of these, 161 were platinum refractory, 151 platinum resistant, and 120 platinum sensitive to their last line of platinum therapy. Of note, 83 patients were primary platinum resistant or refractory (42 and 41, respectively). Median number of prior lines of therapy was 4 (range 2-16), and 27% of patients were treated in 6th or later line. 100% of patients received prior platinum, 99.6% received prior taxane, 81% received prior doxorubicin, 63% received prior bevacizumab, and 59% received prior gemcitabine. In the primary efficacy population (N=45), ORR was 29% (95% CI: 16-44, P=0.0003), disease control rate (DCR) was 71% (95% CI: 56-84), and duration of response (DOR) was 9.2 months (95% CI: 5.9-NE); overall survival (OS) was not reached (95% CI: 18.5-NE). The efficacy outcomes in all 456 patients with measurable disease at baseline treated in 4th or later line demonstrated a DCR of 49% with 2 complete responses (CR), 36 partial responses (PR), and 187 patients with stable disease (SD). The responses were durable with a median DOR of 9.4 months, a clinical benefit rate (CR+PR+SD) at 16 weeks of 29%, and median OS of 17.2 months (95% CI: 14.9-19.8) among all patients treated in 4th or later line. 266 (57.5%) patients had grade ≥3 treatment-related TEAEs. Grade ≥3 thrombocytopenia event (thrombocytopenia or decreased platelet count) by dose at onset of the event was 27.5% at 300 mg, 4.7% at 200 mg, and 2.7% at 100 mg. The other most common grade ≥3 TEAEs were anemia (26.3%) and neutropenia (8.2%). Hematologic TEAEs were most frequent in the first month and decreased in frequency and severity after dose reduction during months 2-3. CONCLUSIONS: Niraparib demonstrated durable anticancer activity in this heavily treated (≥3 lines) ROC population, including platinum-resistant or BRCAwt patients. Toxicities were consistent with previous niraparib studies. DISCLOSURE Funded by TESARO, Inc. Citation Format: Kathleen Moore, Angeles Secord, Melissa Geller, David Miller, Noelle Cloven, Gini Fleming, Andrea E. Wahner Hendrickson, Masoud Azodi, Paul Disilvestro, Amit Oza, Mihaela Cristea, Jonathan S. Berek, John Chan, Yong Li, Kaiming Sun, Katarina Luptakova, Ursula A. Matulonis, Bradley J. Monk. QUADRA: A PHASE 2, OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE SINGLE-AGENT NIRAPARIB TREATMENT IN PATIENTS WITH RELAPSED OVARIAN CANCER (ROC) WHO HAVE RECEIVED ≥3 PRIOR CHEMOTHERAPY REGIMENS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-101.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.009 | 0.002 |
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".