Uptake of targeted therapy in clinical practice among US patients with ovarian cancer.

e18049 Background: Since first approvals for targeted therapies (TTs) in ovarian cancer (OC) patients (pts) in 2014, FDA approvals for TTs including bevacizumab (bev) and PARP inhibitors (PARPis) continue to expand. Approval of front line (1L) indications for bevacizumab (all-comers) and maintenance olaparib (BRCA-mutated) occurred in 2018. Here we describe real-world trends in the use of these TTs. Methods: Data were analyzed from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database of patient-level data, curated via technology-enabled abstraction. We used descriptive statistics and significance tests to describe TT use in pts with OC. Results: We included 2975 treated OC pts diagnosed from 2011-18, with treatment data through 2019. Median follow-up was 32 months. 47% of OC pts received TT during follow-up, 12% of whom received TT during 1L. TTs were given as maintenance therapy in 54% of 1L and 37% of recurrent (2L+) OC pts. 40% of OC pts received bevacizumab anytime, 24% of whom received bevacizumab during 1L. Bevacizumab was given as maintenance therapy in 43% of 1L and 26% of recurrent OC pts. 20% of 2L and 17% of 3L bevacizumab-treated pts were platinum sensitive. From 2012-19, bevacizumab use changed biennially from 10% to 10% to 8% to 18% in FL (p < 0.001), 24% to 35% to 34% to 38% in 2L (p = 0.008), and 21% to 34% to 35% to 36% in 3L (p = 0.06). Corresponding changes in PARPis use were 0% to 0% to 5% to 13% in FL (p = 0.03), 0% to 1% to 11% to 23% in 2L (p = 0.09), and 0% to 3% to 10% to 20% in 3L (p = 0.02). TT use (ever vs. never during follow-up) was more common among pts with stage III-IV tumors (81% vs. 55%), serous histology (90% vs. 75%), history of BRCA (82% vs. 61%) or NGS (38% vs. 13%) testing, and BRCA mutations (21% vs. 33%) (p < 0.001 for all). Conclusions: Bevacizumab and PARPi use is expanding in 1L and 2L treatment; in 1L bevacizumab was more common than PARPis in 2019 (31% vs. 19%). These data reflect the evolving treatment landscape in 1L OC, which is expected to further evolve based on recent evidence from maintenance PARPi monotherapy and PARPi + bevacizumab combination studies. [Table: see text]

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SOLO1 versus SOLO2: Cost-effectiveness of olaparib as maintenance therapy for newly diagnosed and platinum-sensitive recurrent ovarian carcinoma among women with germline BRCA mutations (gBRCAmut).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5545 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5545-5545 ◽

Cited By ~ 3

Author(s):

Juliet Elizabeth Wolford ◽

Krishnansu Sujata Tewari ◽

Su-Ying Liang ◽

Jiaru Bai ◽

Amandeep Kaur Mann ◽

...

Keyword(s):

Cost Effectiveness ◽

Maintenance Therapy ◽

Ovarian Carcinoma ◽

Cost Effective ◽

Parp Inhibitors ◽

Phase 3 ◽

Brca Mutations ◽

Advanced Ovarian Carcinoma ◽

Platinum Sensitive ◽

Maintenance Study

5545 Background: With the December 19, 2018 regulatory approval by the US FDA of olaparib tablets as maintenance therapy for women with deleterious or suspected deleterious germline or somatic BRCAmut advanced ovarian carcinoma, it becomes important to clarify the role of PARP inhibitors in this disease. We evaluated cost-effectiveness of olaparib in the upfront (SOLO1) versus the recurrent maintenance setting (SOLO2). Methods: Data were obtained from SOLO1, the phase 3 placebo-controlled randomized upfront maintenance study among gBRCAmut patients [median PFS greater than 49.8 vs 13.8m: HR 0.30; 95% CI, 0.23-0.41; p < 0.001, NCT01844986] and SOLO2, the phase 3 placebo-controlled randomized maintenance study among gBRCAmut patients with platinum-sensitive recurrence and at least two prior lines of therapy [median PFS 19.1 vs 5.5m: HR 0.30; 95% CI, 0.22-0.41; p < 0.0001, NCT01874353]. Investigator-assessed median PFS and toxicity data from the trials were incorporated in a Markov model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2015, the costs of pre-treatment testing (eg. gBRCAmut), medications, and management of adverse effects were analyzed. Incremental cost-effectiveness ratios (ICERs) per month of life gained and individual PFS-life year saved (PFS-LYS) were also calculated and compared. Results: In SOLO1, cost prior to progression was 1.7x that of SOLO2 ($937,440 vs $564,451). With the extended, estimated median PFS of at least 49.8m for SOLO1 and 19.1m for SOLO2, upfront maintenance therapy was more cost-effective. SOLO 1 was associated with $312,480 PF-LYS per individual patient, while SOLO2 demonstrated $498,045 PF-LYS. Maintenance olaparib was found to be more cost-effective in the 1st-line setting, with an ICER of $12,149 per month of life gained when compared directly to SOLO2. Conclusions: Although the higher cost associated with olaparib in SOLO1 reflects the longer time patients stay on drug due to extended PFS, the ICER supports early use in the disease course as first-line maintenance therapy among women with gBRCAmut advanced ovarian carcinoma.

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Real-world treatment patterns of maintenance therapy in platinum-sensitive recurrent epithelial ovarian cancer: Are some patients missing out?

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e18042 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e18042-e18042

Author(s):

Haley Moss ◽

Angeles Alvarez Secord ◽

Jessica Perhanidis ◽

Carol Hawkes

Keyword(s):

Ovarian Cancer ◽

Maintenance Therapy ◽

Active Surveillance ◽

Real World ◽

Brca Mutation ◽

Treatment Patterns ◽

World Population ◽

Brca Mutations ◽

Platinum Sensitive ◽

Platinum Based Chemotherapy

e18042 Background: The clinical utility of maintenance therapy (MT) for patients with platinum-sensitive recurrent ovarian cancer (PSROC) has been validated in several clinical trials. We assessed real world treatment patterns using a US nationwide electronic health record database. Methods: A retrospective study of patients with PSROC between March 2017 and July 2019 was conducted using the Flatiron Health database. This longitudinal, demographically and geographically diverse de-identified database covers > 2.2 million oncology patients in > 280 cancer clinics. Patients were excluded if second or third line (2L or 3L) platinum-based chemotherapy (PBT) regimens included less than four or more than eight cycles of platinum. Information regarding somatic or germline BRCA mutations and homologous recombination deficiency (HRD) were obtained. Results: 2292 patients with PSROC were identified (had 2L or 3L treatment); 1214 of these received PBT at recurrence; 610 completed the PBT for recurrence on or after March 2017; 351 received 4–8 cycles of PBT; 225 patients had ≥2 months of active surveillance or were receiving MT of PARPi or bevacizumab (B) and were included in this analysis. 183 patients (80%) had BRCA testing and 14 patients (6%) had HRD testing. 46 (20%) had a germline or somatic BRCA mutations (t BRCA), 134 (59%) had a wildtype wt BRCA gene, and 48 (21%) were unknown. Of patients with tBRCA, 63% received a PARP inhibitor (PARPi), 17% received B, 20% received active surveillance. Of patients with wt BRCA, 40% received a PARPi, 24% received B, and 37% received active surveillance. Olaparib was the most commonly used PARPi among tBRCA patients (26%), while niraparib was most commonly used among wt BRCA patients (21%). MT was more common in younger patients, those with a better performance status and with a BRCA mutation. MT use trend increased by 21% during the study period. As PARPi use increased, the use of active surveillance as a post-platinum regimen decreased during the later time periods (Table). Conclusions: In this real world population, the majority of patients with PSROC are receiving maintenance therapy. While genetic testing is improving, universal testing of all patients with ovarian cancer remains the goal. The results provide insight into the shifting treatment patterns for patients with ovarian cancer. [Table: see text]

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EP795 Searching for the best maintenance therapy in platinum-sensitive recurrent ovarian cancer: bevacizumab or PARP-inhibitors? A network meta-analysis

10.1136/ijgc-2019-esgo.846 ◽

2019 ◽

Author(s):

M Bartoletti ◽

G Pelizzari ◽

L Bortot ◽

M Giavarra ◽

MG Vitale ◽

...

Keyword(s):

Ovarian Cancer ◽

Maintenance Therapy ◽

Meta Analysis ◽

Recurrent Ovarian Cancer ◽

Parp Inhibitors ◽

Platinum Sensitive

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Effect of PARP Inhibitors as Maintenance Treatment on Restricted Mean Survival Time in Platinum-Sensitive Recurrent Ovarian Cancer: A Systematic Review and Meta-analysis

Annals of Pharmacotherapy ◽

10.1177/10600280211013489 ◽

2021 ◽

pp. 106002802110134

Author(s):

Masayuki Kaneko

Keyword(s):

Ovarian Cancer ◽

Survival Time ◽

Meta Analysis ◽

Parp Inhibitors ◽

Alternative Measure ◽

Brca Mutations ◽

Mean Survival Time ◽

Platinum Sensitive ◽

Restricted Mean Survival Time ◽

Efficacy Parameter

Background Earlier trials on the efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors in platinum-sensitive relapsed ovarian cancer used the hazard ratio (HR) as an efficacy parameter. Objective The present meta-analysis was focused on improving the robustness and clinical interpretability of the efficacy evaluation of PARP inhibitors using the restricted mean survival time (RMST). Methods A search for relevant studies published up to July 31, 2020, was performed in electronic databases to identify eligible trials comparing PARP inhibitors with placebo. The difference in RMST was used as a PARP inhibitor efficacy parameter. Combined differences in RMST with 95% CIs across studies were calculated using a random-effects model. Results Four trials (6 articles) were assessed, including 1079 patients treated with PARP inhibitors and 598 with placebo. The combined RMST differences for up to 360 days (PARP inhibitors minus placebo: point estimate and 95% CI) among all patients and the patients of subgroups with BRCA mutations, homologous recombination-deficient (HRD) carcinoma, and BRCA wild-type carcinoma were 87 days (95% CI = 71, 102), 112 days (95% CI = 96, 129), 99 days (95% CI = 80, 119), and 69 days (95% CI = 47, 92), respectively. The combined RMST differences for up to 660 and 720 days were also larger among patients with BRCA mutations than among those with HRD carcinoma. Conclusion and Relevance Based on using the RMST difference as an alternative measure to the HR, this meta-analysis suggests that PARP inhibitors are the most effective for patients with BRCA mutations, followed by patients with HRD carcinoma.

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SEOM clinical guideline in ovarian cancer (2020)

Clinical & Translational Oncology ◽

10.1007/s12094-020-02545-x ◽

2021 ◽

Author(s):

A. Redondo ◽

E. Guerra ◽

L. Manso ◽

C. Martin-Lorente ◽

J. Martinez-Garcia ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Guideline ◽

Recurrent Disease ◽

Gynecologic Cancer ◽

Parp Inhibitors ◽

Current Evidence ◽

First Line ◽

Platinum Based Chemotherapy ◽

History Of

AbstractDespite remarkable advances in the knowledge of molecular biology and treatment, ovarian cancer remains the leading cause of death from gynecologic cancer. In the last decade, there have been important advances both in systemic and surgical treatment. However, there is no doubt that the incorporation of PARP inhibitors as maintenance after the response to platinum-based chemotherapy, first in recurrent disease and recently also in first line, will change the natural history of the disease.The objective of this guide is to summarize the current evidence for the diagnosis, treatment, and follow-up of ovarian cancer, and to provide evidence-based recommendations for clinical practice.

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