Reasons for first-line maintenance therapy discontinuation among patients with newly diagnosed advanced ovarian cancer treated in real-world settings.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 290-290
Author(s):  
Jinan Liu ◽  
Premal H. Thaker ◽  
Janvi Sah ◽  
Eric M Maiese ◽  
Linda Kalilani ◽  
...  

290 Background: PARP inhibitor (PARPi) and bevacizumab have been integrated into the first-line (1L) maintenance therapy for patients (pts) with ovarian cancer (OC). However, due to adverse events, the rate of PARPi maintenance discontinuation was 12% in the SOLO1 clinical trial. We aimed to better understand the rate and cause of maintenance therapy discontinuation in real-world practice. Methods: This retrospective cohort study was conducted using de-identified electronic health record (EHR)–derived data from the nationwide Flatiron Health electronic health database. From January 1, 2016, to February 29, 2020, data were obtained for pts with newly diagnosed stage III/IV epithelial OC who received primary debulking surgery followed by 6–9 cycles of 1L platinum-based chemo or neoadjuvant chemo followed by interval debulking surgery. Index date was the end of 1L systemic therapy. Results: Of 675 pts with stage III/IV OC who underwent primary systemic therapy, 144 (21.3%) received 1L maintenance therapy and were included in the analysis. Mean age was 65.0 y. Most pts were treated in community practice (93.1%), had ECOG score of 0–1 at diagnosis (81.3%), and were shown to be BRCA wild type (66.7%). Bevacizumab was the most common 1L maintenance therapy (n = 69, 47.9%), followed by olaparib (n = 46, 31.9%), paclitaxel (n = 18, 12.5%), rucaparib (n = 10, 6.9%), and gemcitabine (n = 1, 0.7%). Overall, 34 (23.6%) pts discontinued 1L maintenance therapy. The most common reason for discontinuation was disease progression (n = 19, 13.2%), followed by treatment-related toxicity (n = 13, 9.0%; Table). Of 56 pts who received PARPi (olaparib or rucaparib) 1L maintenance therapy, 21 (37.5%) pts discontinued treatment: 11 (19.6%) because of disease progression, 9 (16.0%) treatment-related toxicity, and 1 for other reasons. Conclusions: In pts with advanced OC who received 1L maintenance therapy in clinical practice, disease progression was the most common reason for maintenance therapy discontinuation. The rates of toxicity-related discontinuations were comparable with those reported in clinical trials.[Table: see text]

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18710-e18710
Author(s):  
Jinan Liu ◽  
Premal H. Thaker ◽  
Janvi Sah ◽  
Eric M. Maiese ◽  
Oscar Bee ◽  
...  

e18710 Background: With the advent of poly(ADP-ribose) polymerase inhibitors (PARPi), options for first-line (1L) maintenance therapy in ovarian cancer (OC) have evolved in the US. This study described the use of 1L maintenance and assessed predictors of 1L maintenance use among PARPi-eligible patients (pts) with OC in a real-world setting. Methods: This retrospective cohort study included pts with newly diagnosed stage III/IV epithelial OC who received 6–9 cycles of 1L platinum-based chemotherapy (PBC) and primary or interval debulking surgery following neoadjuvant chemotherapy between Jan 1, 2016, and Feb 29, 2020, from the nationwide Flatiron Health electronic health record–derived deidentified database. The end of the last cycle of 1L PBC was defined as the index date. Those pts who started second-line chemotherapy within 2 months of the index date were excluded. Logistic regression was used to analyze variables with regard to 1L maintenance use. Results: In total, 463 pts were included; 21% received maintenance therapy, 79% received active surveillance. Baseline characteristics are shown in the table. Overall maintenance therapy use increased over the study period, from 7.7% to 37.7%. Pts with BRCA wild type were significantly less likely to receive maintenance therapy (odds ratio [OR]: 0.30; 95% CI, 0.16–0.59) than pts with BRCA mutation. Pts treated in 2018 (OR: 2.73; 95% CI, 1.25–5.98) and 2019 (OR: 8.78; 95% CI, 4.15–18.55) were significantly more likely to receive maintenance therapy than pts treated in 2017. Age, race, practice type, ECOG score, and residual disease status were not significant predictors of 1L maintenance use. Conclusions: Nearly 40% of pts with advanced stage OC received upfront maintenance therapy with an increasing trend over time, particularly in those with biomarker guidance. Research is warranted toward addressing barriers to the appropriate use of maintenance therapy.[Table: see text]


2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 294-294
Author(s):  
Jinan Liu ◽  
Premal H. Thaker ◽  
Janvi Sah ◽  
Eric M Maiese ◽  
Oscar Bee ◽  
...  

294 Background: With the advent of poly(ADP-ribose) polymerase inhibitors (PARPi), options for first-line (1L) maintenance therapy in ovarian cancer (OC) have evolved in the US. This study described the use of 1L maintenance and assessed predictors of 1L maintenance use among PARPi-eligible patients (pts) with OC in a real-world setting. Methods: This retrospective cohort study included pts with newly diagnosed stage III/IV epithelial OC who received 6–9 cycles of 1L platinum-based chemotherapy (PBC) and primary or interval debulking surgery following neoadjuvant chemotherapy between Jan 1, 2016, and Feb 29, 2020, from the nationwide Flatiron Health electronic health record–derived deidentified database. The end of the last cycle of 1L PBC was defined as the index date. Those pts who started second-line chemotherapy within 2 months of the index date were excluded. Logistic regression was used to analyze variables with regard to 1L maintenance use. Results: In total, 463 pts were included; 21% received maintenance therapy, 79% received active surveillance. Baseline characteristics are shown in the table. Overall maintenance therapy use increased over the study period, from 7.7% to 37.7%. Pts with BRCA wild type were significantly less likely to receive maintenance therapy (odds ratio [OR]: 0.30; 95% CI, 0.16–0.59) than pts with BRCA mutation. Pts treated in 2018 (OR: 2.73; 95% CI, 1.25–5.98) and 2019 (OR: 8.78; 95% CI, 4.15–18.55) were significantly more likely to receive maintenance therapy than pts treated in 2017. Age, race, practice type, ECOG score, and residual disease status were not significant predictors of 1L maintenance use. Conclusions: Nearly 40% of pts with advanced stage OC received upfront maintenance therapy with an increasing trend over time, particularly in those with biomarker guidance. Research is warranted toward addressing barriers to the appropriate use of maintenance therapy.[Table: see text]


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18707-e18707
Author(s):  
Jinan Liu ◽  
John Chan ◽  
Janvi Sah ◽  
Eric M. Maiese ◽  
Oscar Bee ◽  
...  

e18707 Background: Options for first-line (1L) maintenance therapy in ovarian cancer (OC) have evolved in the US in recent years, particularly with FDA approvals of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi). Olaparib was approved in 2018 for 1L maintenance treatment of patients (pts) with advanced OC with BRCA mutation and in 2020 as combination therapy with bevacizumab for 1L maintenance treatment of pts with homologous recombination deficient (HRd)–positive tumors. Additionally, the FDA approved niraparib in 2020 for maintenance treatment of pts with advanced OC regardless of tumor biomarker status. This study aimed to describe use and outcomes of 1L maintenance vs. active surveillance (AS) among PARPi-eligible pts with OC in a real-world setting prior to the most recent 2020 FDA approvals. Methods: This retrospective cohort study included pts with newly diagnosed stage III/IV OC who received 6–9 cycles of 1L platinum-based chemotherapy (PBC) and either primary debulking surgery or interval debulking surgery following neoadjuvant chemotherapy between January 1, 2016, and February 29, 2020, regardless of biomarker status, from the Flatiron Health database, a longitudinal electronic health record-derived database consisting of de-identified patient-level data that are curated via technology-enabled abstraction. The end of the last cycle of 1L PBC was defined as the index date. Pts who started second-line (2L) treatment within 2 months of the index date were excluded. Primary endpoint was time to initiation of 2L systemic therapy (as a surrogate for progression) or death. Inverse probability of treatment weighting and Cox proportional hazard model were used to adjust for baseline differences among pts on maintenance therapy and pts on AS. Results: A total of 463 pts were included in the study, 87.7% from community practices and 12.3% from academic institutions. Of the pts included, 21.0% received maintenance therapy, while 79.0% did not. Of those who received maintenance therapy, 48.5% received bevacizumab, 40.2% received PARPi (olaparib, rucaparib), and 11.3% received paclitaxel. Median progression-free survival (PFS) for pts who received 1L maintenance therapy was 16.1 months, compared with 12.2 months in pts who did not receive 1L maintenance therapy. After adjusting for baseline differences in characteristics and demographics, including age, race, stage of cancer, and BRCA status, pts on maintenance therapy had a statistically significant, 29% lower risk of progression or death than those receiving AS (hazard ratio: 0.71; 95% CI, 0.52–0.99; P= 0.04). Conclusions: In this real-world analysis, the majority of pts did not receive maintenance therapy; however, a PFS benefit was found in those receiving maintenance therapy. Further studies are needed to understand how biomarker status drives practice patterns.


2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 292-292
Author(s):  
Shiru Liu ◽  
Wing Chan ◽  
Genevieve Bouchard-Fortier ◽  
Stephanie Lheureux ◽  
Sarah Ferguson ◽  
...  

292 Background: Initial treatment of epithelial ovarian cancer (EOC) consists of combination of cytoreductive surgery (CSR) and/or chemotherapy. Targeted therapies such as bevacizumab have shown to improve outcomes in a subset population with high-risk features. Real-world patterns of systemic therapy delivery in EOC in the modern era are not well understood. Our objective is to evaluate the patterns of first-line systemic treatment of advanced EOC in Ontario, focusing on adoption of bevacizumab, which was approved for use in 2016. Methods: We conducted a retrospective, population cohort study using administrative databases held at the ICES in Ontario, Canada. Patients diagnosed with non-mucinous EOC between 2014 and 2018 were identified from the Ontario Cancer Registry; early-stage disease was excluded. Information on systemic therapy was obtained from Activity Level Reporting and New Drug Funding Program databases. Provider of care (gynecologic oncologist vs medical oncologist) information was obtained from billing codes. Academic cancer centers were identified using validated systemic facility codes from Cancer Care Ontario. Statistical analyses include descriptive statistics, t-tests, and multivariable logistic regression using SAS. Results: Out of 4,680 cases diagnosed with EOC during the study period, 3,632 (77.6%) were considered advanced stage. Median age of cohort was between 65-70, and the majority had Charlson score of 1-2 (97%) and are urban (91.8%). A total of 3,181 (87.6%) patients underwent CRS and 2,722(74.9%) patients underwent chemotherapy. Of those who received chemotherapy, 1,259 (46.2%) received neoadjuvant chemotherapy, 1,012 (37.2%) received upfront CRS, and 451(16.5%) received chemotherapy only. The majority of chemotherapy was delivered by gynecologic oncologists (60.6%) and in academic cancer centres (61.7%). There was no significant difference in use of neoadjuvant chemotherapy between medical oncologists and gynecologic oncologists (p = 0.67). Only 53 chemotherapy patients (1.9%) received bevacizumab containing-regimen in the first-line setting. Medical oncologists were 4 times more likely to administer bevacizumab-containing regimen compared to gynecologic oncologists (OR 4.03, 95% CI.29 – 7.36) after adjusting for age, stage, Charlson score and rurality score on logistic regression. Delivery of bevacizumab is relatively higher in non-academic cancer centres (OR 2.61, 95% CI 2.32- 2.94) while 83% of intraperitoneal chemotherapy is delivered in academic cancer centres. Conclusions: Patterns of care of EOC in Ontario remain heterogenous between care providers and institutions, while uptake of bevacizumab for first-line treatment of EOC remains low. Factors leading to low uptake and real-world outcomes should be explored.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5598-TPS5598 ◽  
Author(s):  
Philipp Harter ◽  
Mariusz Bidziński ◽  
Nicoletta Colombo ◽  
Anne Floquet ◽  
Maria Jesús Rubio Pérez ◽  
...  

TPS5598 Background: Ovarian cancer (OC) is the leading cause of death from gynecologic cancers in US women. Despite high response rates to first-line treatment, ~70% of patients (pts) relapse within 3 years and then remain largely incurable. First-line treatment needs to be improved to achieve long-term remission in pts and improve the cure rate. The Phase III SOLO1 trial showed a meaningful clinical benefit for olap maintenance therapy in newly diagnosed OC pts with a BRCA mutation (Moore et al N Engl J Med 2018). Preliminary data suggest that combining a PD-L1 inhibitor, anti-angiogenic and PARP inhibitor (triplet therapy) may achieve a synergistic antitumor effect. The DUO-O study (NCT03737643) evaluates the efficacy and safety of treatment combinations involving standard-of-care platinum-based chemotherapy (chemo), VEGF inhibitor bev, anti-PD-L1 antibody durva and PARP inhibitor olap, in women with newly diagnosed advanced OC. Methods: Eligible pts for this double-blind, randomized, Phase III study must have newly diagnosed, advanced, high-grade epithelial OC and either have completed primary surgery or plan to have interval debulking surgery. Depending on their tumor BRCA mutation (tBRCAm) status (determined by central test), pts will join one of two independent cohorts. Pts in the non-tBRCAm cohort (n~906) will be randomized (1:1:1) before cycle 2 to: a) chemo + bev + placebo (for 6 cycles) followed by bev (15 mg/kg [total 15 months]) + placebo maintenance treatment (IV and tablets); b) chemo + bev + durva (6 cycles) followed by bev + durva (1120 mg q3w [total 15 months]) + placebo (tablets) maintenance treatment; or c) chemo + bev + durva (6 cycles) followed by bev + durva + olap (300 mg bd tablets [24 months]) maintenance treatment. Pts in the open-label tBRCAm cohort (n~150) will receive 6 cycles of chemo + durva followed by durva + olap maintenance therapy, with optional use of bev. The primary endpoint of progression-free survival will be assessed by modified RECIST 1.1. Key secondary endpoints include overall survival, overall response rate and duration of response. Enrollment began in January 2019. Clinical trial information: NCT03737643.


2021 ◽  
Author(s):  
Shannon N Westin ◽  
Melinda Louie-Gao ◽  
Divya Gupta ◽  
Premal H Thaker

Aim: Patient chart data from the USA during the period of January 2011 through October 2018 were used to assess risk factors for progression in advanced ovarian cancer after response to first-line platinum-based chemotherapy. Patients & methods: Patients with stage III/IV ovarian cancer who completed first-line platinum-based chemotherapy after primary or interval debulking surgery were identified from the Flatiron Health database. Cox proportional hazards modeling was used to assess associations between baseline factors and time to next treatment (TTNT) or overall survival (OS). Results: Patients at stage IV or who received interval debulking surgery had shorter TTNT and OS than patients at stage III or who received primary debulking surgery, respectively. OS was worse in patients with residual disease and in BRCA wild-type. Conclusion: Multiple factors were associated with shorter TTNT or OS in this retrospective real-world analysis.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18087-e18087
Author(s):  
Elizabeth A. Szamreta ◽  
Matthew J. Monberg ◽  
Kaushal Desai ◽  
Xin Chen ◽  
Megan Othus

e18087 Background: A critical question in determining long-term prognosis for women with newly diagnosed ovarian cancer (OC) is whether or not their risk of death changes with time. The emergence of large, well-populated real-world datasets permits assessment of conditional survival (CS) given prior overall survival (OS) or progression-free survival (PFS). Methods: The Tempus EMR clinical dataset consists of patients from both National Cancer Institute designated centers and a sample of community oncology centers in the U.S. This study included adult women with a primary diagnosis of ovarian, fallopian tube, or peritoneal cancer from 1982 to 2018; women treated with a poly-ADP ribose polymerase (PARP) inhibitor were excluded due to low numbers & limited follow-up (final n = 2,031). The effects of patient attributes on OS were estimated using Cox regression. We calculated CS as the Kaplan-Meier probability of surviving an additional y years (from first line chemotherapy initiation), given no OS or PFS event in the previous x (< y) years. Results: Median age was 61 years and 68% of patients were Caucasian. The majority (92%) had epithelial histology, 58% were stage 3 or 4, and 49% were ECOG 0 or 1. Median OS was 37 months (95% CI: 36-39), and OS differed by age, stage, and performance status; adjusted hazard ratios (HRs) for OS were 1.3 (95% CI: 1.0, 1.5) for age > 65 versus < 45, 2.4 for stage 4 versus stage 1 (95% CI: 1.7, 3.4), and 1.4 for ECOG 2 to 4 versus 0 or 1 (95% CI: 1.2, 1.7). Conditional 1- or 5-year survival rate did not vary based on prior OS. However, CS rates among women alive without disease progression increased with time: 1-year and 5-year survival rates (with 95% CI) were 86% (84-87) and 28% (26-31), respectively, in women alive without progression at 6 months, but increased to 94% (89-97) and 53% (44-62) in women alive without progression at 3 years. Conclusions: Long-term prognosis, as shown by conditional survival rates, did not improve based on time alive since initiation of chemotherapy. However, women with longer time without disease progression had lower rates of death and a better prognosis. [Table: see text]


2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110073
Author(s):  
Jin Xu ◽  
Xinhui Zhang ◽  
Shanglong Feng ◽  
Na Zhao ◽  
Xin Hu ◽  
...  

Objective As first-line treatments for newly diagnosed adult immune thrombocytopenia (ITP), high-dose dexamethasone (HD-DXM) and conventional-dose prednisone achieve good initial responses, but their long-term efficacy is poor. To improve the long-term outcome of newly diagnosed ITP, we explored the efficacy and safety of HD-DXM with sequential prednisone maintenance therapy. Methods This retrospective study in a real-world setting assessed 72 consecutive newly diagnosed ITP patients administered first-line HD-DXM with sequential prednisone maintenance therapy from 1 June 2016 to 31 December 2019. Results Seventy patients obtained response (97.2%), and 55 achieved sustained response (SR) (76.4%). Fifty-three obtained complete remission (CR) (73.6%), and 39 achieved continuous CR at 6 months (54.2%). Among 36 anti-nuclear antibody-positive patients, 100% achieved response, and 28 achieved CR (77.8%). Among 24 antithyroid antibody-positive patients, 23 (95.8%) achieved response, and 20 achieved CR (83.3%). For patients with initial response, the 12-month probability of SR was 78.6%. For patients with initial CR, the 12-month probability of continuous CR was 64.2%. At 12 months, 21.4% of patients with initial response and 11.3% of patients with initial CR showed loss of treatment response. Conclusions HD-DXM with sequential prednisone as the first-line treatment for newly diagnosed ITP patients may achieve good clinical efficacy.


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