Efficacy and safety of maintenance olaparib and bevacizumab in ovarian cancer patients aged ≥65 years from the PAOLA-1/ENGOT-ov25 trial

Sabatier, Renaud; Rousseau, Frédérique; Joly, Florence; Cropet, Claire; Montegut, Coline; Frindte, J; Cinieri, Saverio; Alía, E.M. Guerra; Polterauer, Stephan; Yoshida, Hiroyuki; Vergote, Ignace; Colombo, Nicoletta; Hietanen, Sakari; Largillier, R.; Canzler, Ulrich; Gratet, Alain; Marmé, Frederik; Favier, Laure; Pujade-Lauraine, Éric

doi:10.1016/j.ejca.2022.11.029

Cited by 12 publications

(7 citation statements)

References 42 publications

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“…While a previous systematic review of olaparib use on ovarian cancer patients reported that approximately one‐third of patients (1435/4364) in eight RCTs were 65 years or older, and hematologic safety was similar to that seen in younger patients 6 . Another subgroup analysis of an RCT found that older patients enrolled in PAOLA‐1 achieved similar progression‐free survival benefits compared with younger patients, with a similar safety profile 7 …”

Section: Discussionmentioning

confidence: 96%

“…6 Another subgroup analysis of an RCT found that older patients enrolled in PAOLA-1 achieved similar progression-free survival benefits compared with younger patients, with a similar safety profile. 7 There are several potential reasons for this practice. First, elderly patients may have a higher incidence of hematologic toxicity compared to what has been observed in RCTs.…”

Section: Discussionmentioning

confidence: 99%

“…A systematic review of olaparib use on ovarian cancer patients reported that approximately one‐third of patients (1435/4364) in eight RCTs were 65 years or older, and hematologic safety was similar to that seen in younger patients 6 . Another subgroup analysis of an RCT found that older patients enrolled in PAOLA‐1 achieved similar progression‐free survival benefits compared with younger patients, with a similar safety profile 7 . Thus, though studies have evaluated the effects of olaparib on the elderly population, these evaluations are limited to subgroup analyses in the setting of an RCT, and there is a dearth of real‐world evidence on the use of olaparib in aging populations, especially those using national‐level data.…”

Section: Introductionmentioning

confidence: 96%

“…6 Another subgroup analysis of an RCT found that older patients enrolled in PAOLA-1 achieved similar progression-free survival benefits compared with younger patients, with a similar safety profile. 7 Thus, though studies have evaluated the effects of olaparib on the elderly population, these evaluations are limited to subgroup analyses in the setting of an RCT, and there is a dearth of real-world evidence on the use of olaparib in aging populations, especially those using national-level data. Elderly patients may require reduced doses due to hematologic toxicity and are worthy of independent evaluation.…”

Section: Introductionmentioning

confidence: 99%

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Dose reduction of olaparib in older patients: Insights from an analysis of a National Database in Japan

Sato,

Goto

2023

J of Obstet and Gynaecol

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AimAlthough the advent of a poly polymerase inhibitors has greatly advanced the tailoring of cancer treatment, there is a dearth of real‐world evidence on the actual use of olaparib in aging populations, especially those using national‐level data.MethodsWe extracted and analyzed all prescriptions of olaparib in female outpatients from the National Database Open Data Japan (NDB Open Data) from April 2019 to March 2021. The recommended standard dose of olaparib is four tablets of the 150 mg formulation per day, while the 100 mg formulation of olaparib can be considered as an alternative dose in the occurrence of hematologic toxicity. We calculated the proportion of 100 mg compared to the 150 mg prescriptions across age groups. A Cochrane–Armitage trend test was used to examine the association of age groups with the proportion of 100 mg prescriptions.ResultsThe total number of prescriptions of the 100 mg formulation and the 150 mg formulation were 1449 222, and 4233 625, respectively. Overall, 45.1% (2567 513/5682 847 prescriptions) of olaparib were prescribed for patients 65 years of age or older in females. Stratified by age group, the proportion of 100 mg compared to the 150 mg prescriptions significantly increased with age (p < 0.0001).ConclusionsGiven that the 100 mg formulation of olaparib can be considered as an alternative dose in Japan in the occurrence of hematologic toxicity, our observations indicate the dose reduction of olaparib in older patients in Japan. Further investigations are necessary to assess its efficacy and safety at a reduced dose.

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Section: Discussionmentioning

confidence: 96%

“…6 Another subgroup analysis of an RCT found that older patients enrolled in PAOLA-1 achieved similar progression-free survival benefits compared with younger patients, with a similar safety profile. 7 There are several potential reasons for this practice. First, elderly patients may have a higher incidence of hematologic toxicity compared to what has been observed in RCTs.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

“…6 Another subgroup analysis of an RCT found that older patients enrolled in PAOLA-1 achieved similar progression-free survival benefits compared with younger patients, with a similar safety profile. 7 Thus, though studies have evaluated the effects of olaparib on the elderly population, these evaluations are limited to subgroup analyses in the setting of an RCT, and there is a dearth of real-world evidence on the use of olaparib in aging populations, especially those using national-level data. Elderly patients may require reduced doses due to hematologic toxicity and are worthy of independent evaluation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dose reduction of olaparib in older patients: Insights from an analysis of a National Database in Japan

Sato,

Goto

2023

J of Obstet and Gynaecol

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“…This method has demonstrated clinical utility and predictive value in ovarian cancer, and can detect up to 50% of cases ( 5 ). An NGS-based commercial test, has been extensively evaluated in clinical trials; it determines the combined status of LOH, TAI and LST, for the calculation of GIS, along with BRCA1/2 gene mutation analysis ( 4 , 25 , 26 ). Positivity is considered a GIS score of ≥42 and/or a BRCA1/2 somatic or germline mutation ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

RediScore: Prospective validation of a pipeline for homologous recombination deficiency analysis

Tsantikidi,

Papazisis,

Floros

et al. 2023

Oncol Lett

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Tumors harboring homologous recombination deficiency (HRD) are considered optimal candidates for poly(ADP-ribose) polymerase 1 (PARP) inhibitor treatment. Such deficiency can be detected by analyzing breast cancer type ( BRCA)1/2 gene mutations, as well as mutations in other genes of the homologous recombination pathway. The algorithmic measurement of the HRD effect by identifying genomic instability (GI) has been used as biomarker. As compared with the direct measurement of somatic gene alterations, this approach increases the number of patients who could benefit from PARP inhibitor treatment. In the present study, the performance of the Oncoscan CNV assay, accompanied by appropriate bioinformatic algorithms, was evaluated for its performance in GI calculation and was compared with that of a validated next-generation sequencing (NGS) test (myChoice HRD test). In addition, the clinical utility of the GI score (GIS) and BRCA1/2 tumor analysis were investigated in a cohort of 444 patients with ovarian cancer. For that reason, single nucleotide polymorphism (SNP) arrays and appropriate bioinformatics algorithms were used to calculate GIS in 29 patients with ovarian cancer with known GIS status using a validated NGS test. Furthermore, BRCA1/2 analysis results were compared between the aforementioned assay and the amplicon-based Oncomine ™ BRCA Research Assay. BRCA1/2 analysis was performed in 444 patients with ovarian cancer, while GIS was calculated in 175 BRCA1/2 -negative cases. The bioinformatics algorithm developed for GIS calculation in combination with NGS BRCA1/2 analysis (RediScore), and the OncoscanR pipeline exhibited a high overall agreement with the validated test (93.1%). In addition, the Oncomine NGS assay had a 100% agreement with the validated test. The BRCA1/2 mutation frequency was 26.5% in the examined patients with ovarian cancer. GIS was positive in 40% of the BRCA1/2 -negative cases. The RediScore bioinformatics algorithm developed for GIS calculation in combination with NGS BRCA1/2 analysis is a viable and effective approach for HRD calculation in patients with ovarian cancer, offering a positive prediction for PARP inhibitor responsiveness in 55% of the patients.

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First-line PARP inhibitor maintenance treatment in ovarian carcinoma for older adult women: a review of the current literature

Masvidal Hernandez,

Cros Costa,

Salvador Coloma

et al. 2024

Clin Transl Oncol

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Efficacy and safety of maintenance olaparib and bevacizumab in ovarian cancer patients aged ≥65 years from the PAOLA-1/ENGOT-ov25 trial

Cited by 12 publications

References 42 publications

Dose reduction of olaparib in older patients: Insights from an analysis of a National Database in Japan

Dose reduction of olaparib in older patients: Insights from an analysis of a National Database in Japan

RediScore: Prospective validation of a pipeline for homologous recombination deficiency analysis

First-line PARP inhibitor maintenance treatment in ovarian carcinoma for older adult women: a review of the current literature

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