Patient-centred outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance olaparib or placebo (SOLO1): a randomised, phase 3 trial

Friedlander, Michael; Moore, Kathleen N.; Colombo, Nicoletta; Scambia, Giovanni; Oaknin, Ana; Lisyanskaya, Alla; Sonke, Gabe S.; Gourley, Charlie; Banerjee, Susana; Oza, Amit M.; González-Martín, Antonio; Aghajanian, Carol; Bradley, William H.; Liu, Joyce F.; Mathews, Cara; Selle, Frédèric; Lortholary, Alain; Lowe, Elizabeth S.; Hettle, Robert; Flood, Emuella; Parkhomenko, Elena; DiSilvestro, Paul

doi:10.1016/s1470-2045(21)00098-x

Cited by 46 publications

(27 citation statements)

References 29 publications

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“…In the SOLO1 trial comparing maintenance olaparib with placebo in women with newly diagnosed platinum-sensitive advanced OC and a BRCA mutation, mean QA-PFS and TWiST gains of 12.17 and 12.92 months, respectively, were reported for olaparib versus placebo. 38 These findings, while in concordance with our own data, are not directly comparable with the QA-PFS and TWiST gains reported for niraparib, owing to differences between the patient populations in the SOLO1 and PRIMA trials. Patients in SOLO1 had a lower risk of disease progression or death than the PRIMA population, based on prognostic factors; the PRIMA trial also enrolled patients with non-mutated BRCA OC, in addition to those with a BRCA mutation.…”

Section: Discussionsupporting

confidence: 77%

Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial

et al. 2022

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Background: The PRIMA phase 3 trial showed niraparib significantly prolongs median progression-free survival (PFS) versus placebo in patients with advanced ovarian cancer (OC) responsive to first-line platinum-based chemotherapy, including those who had tumors with homologous recombination deficiency (HRd). This analysis of PRIMA examined the quality-adjusted PFS (QA-PFS) and quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) of patients on maintenance niraparib versus placebo. Methods: Patients were randomized 2:1 to receive once-daily maintenance niraparib ( n = 487) or placebo ( n = 246). QA-PFS was defined as the PFS of patients adjusted for their health-related quality of life (HRQoL) prior to disease progression, measured using European Quality of Life Five-Dimension (EQ-5D) questionnaire index scores from the PRIMA trial. Q-TWiST was calculated by combining data on PFS, duration of symptomatic grade ⩾2 adverse events (fatigue or asthenia, nausea, vomiting, abdominal pain, and abdominal bloating) prior to disease progression, and EQ-5D index scores. Analyses used data collected up to the last date of PFS assessment (May 17, 2019). Results: The restricted mean QA-PFS was significantly longer with niraparib versus placebo in the HRd ( n = 373) and overall intention-to-treat (ITT; n = 733) populations (mean gains of 6.5 [95% confidence interval; CI, 3.9–8.9] and 4.1 [95% CI, 2.2–5.8] months, respectively). There were also significant improvements in restricted mean Q-TWiST for niraparib versus placebo (mean gains of 5.9 [95% CI, 3.5–8.6] and 3.5 [95% CI, 1.7–5.6] months, respectively) in the HRd and ITT populations. Conclusions: In patients with advanced OC, first-line niraparib maintenance was associated with significant gains in QA-PFS and Q-TWiST versus placebo. These findings demonstrate that niraparib maintenance treatment is associated with a PFS improvement and that treatment benefit is maintained even when HRQoL and/or toxicity data are combined with PFS in a single measure. Trial registration: ClinicalTrials.gov: NCT02655016; trial registration date: January 13, 2016 Plain language summary Background: In a large clinical trial called PRIMA, patients with advanced cancer of the ovary (ovarian cancer) were given either niraparib (a type of cancer medicine) or placebo (a pill containing no medicine/active substances) after having chemotherapy (another type of cancer medicine). Taking niraparib after chemotherapy is called maintenance therapy and aims to give patients more time before their cancer returns or gets worse than if they were not given any further treatment. In the PRIMA trial, patients who took niraparib did have more time before their cancer progressed than if they took placebo. However, it is important to consider patients’ quality of life, which can be made worse by cancer symptoms and/or side effects of treatment. Here, we assessed the overall benefit of niraparib for patients in PRIMA. Methods: Both the length of time before disease progression (or survival time) and quality of life were considered using two different analyses: ● The first analysis was called quality-adjusted PFS (QA-PFS) and looked at how long patients survived with good quality of life. ● The second analysis was called quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) and looked at how long patients survived without cancer symptoms or treatment side effects. Results: The PRIMA trial included 733 patients; 487 took niraparib and 246 took placebo. Around half of the patients in both groups had a type of ovarian cancer that responds particularly well to drugs like niraparib – they are known as homologous recombination deficiency (HRd) patients. ● When information on quality of life (collected from patient questionnaires) and survival was combined in the QA-PFS analysis, HRd patients who took niraparib had approximately 6.5 months longer with a good quality of life before disease progression than those who took placebo. In the overall group of patients (including HRd patients and non-HRd patients), those who took niraparib had approximately 4 months longer than with placebo. ● Using the second analysis (Q-TWiST) to combine information on survival with cancer symptoms and treatment side effects, the HRd patients taking niraparib had approximately 6 months longer without cancer symptoms or treatment side effects (such as nausea or vomiting) than patients taking placebo. In the overall group of patients, those taking niraparib had approximately 3.5 months longer without these cancer symptoms/side effects than patients receiving placebo. Conclusions: These results show that the survival benefits of niraparib treatment remain when accounting for patients’ quality of life. These benefits were seen not only in HRd patients who are known to respond better to niraparib, but in the overall group of patients who took niraparib.

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Section: Discussionsupporting

confidence: 77%

Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial

et al. 2022

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“…Time to deterioration of quality of life as measured by the EQ-5D-5L questionnaire was longer with pembrolizumab than with placebo (58.2% versus 44.8% free from deterioration at 12-months). The improved quality of life with immune checkpoint inhibition is noteworthy since it is consistent with the improvement observed in the cemiplimab arm of EMPOWER-Cervical 1/GOG-3016;ENGOT-cx9 trial for second or third line systemic treatment ( Tewari, et al, 2021 ) and most of our therapeutic trials have reported no detriment in quality of life with investigational therapy ( Friedlander et al, 2021 , Ray-Coquard et al, 2019 , Pothuri et al, 2020 ).…”

Section: Current State Of Cervical Cancer Therapysupporting

confidence: 77%

Cervical cancer – times… they are a changing: A report from the Society of Gynecologic Oncology journal club

Walsh

Leath

Mayadev

et al. 2022

Gynecologic Oncology Reports

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“…A subgroup analysis found that olaparib maintenance reduced the risk of progression or death in patients who underwent PDS (HR=0.31; 95%CI=0.21-0.46) and in those who underwent IDS (HR=0.37; 95%CI=0.24-0.58), in patients with RD after surgery (HR=0.44; 95%CI=0.25-0.77) and in those without RD after surgery (HR=0.33; 95%CI=0.23-0.46), in complete responders (HR=0.34, 95%CI=0.24-0.47) and in partial responders at baseline (HR=0.31; 95%CI=0.18-0.52), and in patients with BRCA1 mutation (HR=0.41; 95%CI=0.30-0.56) as well as in those with BRCA2 mutations (HR=0.20; 95%CI=0.10-0.37) (37). These PFS improvements were obtained without clinically meaningful changes in healthrelated quality of life (38).…”

Section: Trials With Parp Inhibitorsmentioning

confidence: 88%

Randomized Clinical Trials and Real World Prospective Observational Studies on Bevacizumab, PARP Inhibitors, and Immune Checkpoint Inhibitors in the First-Line Treatment of Advanced Ovarian Carcinoma: A Critical Review

Gadducci¹,

Cosio²

2021

Anticancer Res

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third cytotoxic agent to standard PTX/CBDCA, failed to improve the clinical outcomes (14)(15)(16)(17)(18)(19).In recent years the implementation of biological knowledge on ovarian carcinoma and especially on the predictive and prognostic relevance of BRCA and homologous recombination status, as well as the addition of biological agents, such as BEV and poly(ADP-ribose) polymerase inhibitors (PARPi) to first-line chemotherapy have improved patient prognosis.In this review we analyze the clinical trials on these issues, in order to offer a possible algorithm that may help the clinicians in the rational use of BEV and PARPi in patients with newly diagnosed advanced ovarian carcinoma. Trials With BevacizumabGynecologic Oncology Group (GOG) 218 phase III trial randomized patients with advanced ovarian carcinoma to receive i) PTX+CBDCA for 6 cycles with placebo added in cycles 2 through 22; or ii) the same chemotherapy plus BEV added in cycles 2 through 6 and followed by placebo added in cycles 7 through 22; or iii) the same chemotherapy plus BEV added in cycles 2 through 22 (20) (BEV throughout). The BEV-throughout arm achieved a better PFS compared with the chemotherapy arm alone [hazard ratio (HR)=0.717, p<0.001], which was the primary endpoint of the study (Table I and Table II).Grade ≥2 hypertension was significantly more common with BEV than with placebo, whereas there were no significant differences among the three arms in terms of severe gastrointestinal adverse events or proteinuria. The final analysis of the study confirmed the lack of OS benefit from both concurrent BEV and concurrent and maintenance BEV compared with chemotherapy only in the whole population (HR=1.06, 95%CI=0.94-1.20 and HR=0.96, 95%CI=0.85-1.09, respectively) (21). However, in an exploratory subset analysis the BEV-throughout arm was associated with a better OS compared with the chemotherapy only arm in patients with stage IV disease (median, 42.8 versus 32.6 months, HR=0.75; 95%CI=0.59-0.95).In the International Collaboration on Ovarian Neoplasms (ICON7) trial, patients with high-risk stage IA-IIA or stage IIB-IV ovarian carcinoma were randomized to PTX+CBDCA for 6 cycles or the same chemotherapy plus BEV 7.5 mg/kg given concurrently for 5 or 6 cycles and continued for 12 additional cycles (22) (Table I). PFS was better for the BEV arm (HR=0.81, p=0.004), and the PFS difference between BEV-and non-BEV-treated patients peaked at 12 months, corresponding to the end of BEV treatment, with an improvement in PFS at this time of approximately 15.1% but afterwards this advantage tended to decrease (Table II). In a subsequent exploratory analysis, the addition of BEV improved OS (median, 39.7 versus 30.2

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Patient-centred outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance olaparib or placebo (SOLO1): a randomised, phase 3 trial

Cited by 46 publications

References 29 publications

Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial

Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial

Cervical cancer – times… they are a changing: A report from the Society of Gynecologic Oncology journal club

Randomized Clinical Trials and Real World Prospective Observational Studies on Bevacizumab, PARP Inhibitors, and Immune Checkpoint Inhibitors in the First-Line Treatment of Advanced Ovarian Carcinoma: A Critical Review

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