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4. Estimating health-state utility values for patients with recurrent ovarian cancer using Functional Assessment of Cancer Therapy – General mapping algorithms

Author

Hettle R, Borrill J, Suri G, and Wulff J

Subjects
Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Robert Hettle,1 John Borrill,2 Gaurav Suri,1 Jerome Wulff1 1Parexel Consulting, London, 2AstraZeneca, Macclesfield, UK Objectives: In the absence of EuroQol 5D data, mapping algorithms can be used to predict health-state utility values (HSUVs) for use in economic evaluation. In a placebo-controlled Phase II study of olaparib maintenance therapy (NCT00753545), health-related quality of life was measured using the Functional Assessment of Cancer Therapy – Ovarian (FACT-O) questionnaire. Our objective was to generate HSUVs from the FACT-O data using published mapping algorithms. Materials and methods: Algorithms were identified from a review of the literature. Goodness-of-fit and patient characteristics were compared to select the best-performing algorithm, and this was used to generate base-case HSUVs for the intention-to-treat population of the olaparib study and for patients with breast cancer antigen mutations. Results: Four FACT – General (the core component of FACT-O) mapping algorithms were identified and compared. Under the preferred algorithm, treatment-related adverse events had no statistically significant effect on HSU (P>0.05). Discontinuation of the study treatment and breast cancer antigen mutation status were both associated with a reduction in HSUVs (–0.06, P=0.0009; and –0.03, P=0.0511, respectively). The mean HSUV recorded at assessment visits was 0.786. Conclusion: FACT – General mapping generated credible HSUVs for an economic evaluation of olaparib. As reported in other studies, different algorithms may produce significantly different estimates of HSUV. For this reason, it is important to test whether the choice of a specific algorithm changes the conclusions of an economic evaluation. Keywords: platinum sensitive ovarian cancer, EQ 5D, maintenance therapy, olaparib

Published
2015

6. Population-adjusted indirect treatment comparison of the SOLO1 and PAOLA-1/ENGOT-ov25 trials evaluating maintenance olaparib or bevacizumab or the combination of both in newly diagnosed, advanced BRCA-mutated ovarian cancer

Author

Vergote, I, Ray-Coquard, I, Anderson, D, Cantuaria, G, Colombo, N, Garnier-Tixidre, C, Gilbert, L, Harter, P, Hettle, R, Lorusso, D, Maenpaa, J, Marth, C, Matsumoto, K, Ouwens, M, Poveda, A, Raspagliesi, F, Rhodes, K, Rubio Perez, M, Shapira-Frommer, R, Shikama, A, Sikorska, M, Moore, K, Disilvestro, P, Vergote I., Ray-Coquard I., Anderson D. M., Cantuaria G., Colombo N., Garnier-Tixidre C., Gilbert L., Harter P., Hettle R., Lorusso D., Maenpaa J., Marth C., Matsumoto K., Ouwens M., Poveda A., Raspagliesi F., Rhodes K., Rubio Perez M. J., Shapira-Frommer R., Shikama A., Sikorska M., Moore K., DiSilvestro P., Vergote, I, Ray-Coquard, I, Anderson, D, Cantuaria, G, Colombo, N, Garnier-Tixidre, C, Gilbert, L, Harter, P, Hettle, R, Lorusso, D, Maenpaa, J, Marth, C, Matsumoto, K, Ouwens, M, Poveda, A, Raspagliesi, F, Rhodes, K, Rubio Perez, M, Shapira-Frommer, R, Shikama, A, Sikorska, M, Moore, K, Disilvestro, P, Vergote I., Ray-Coquard I., Anderson D. M., Cantuaria G., Colombo N., Garnier-Tixidre C., Gilbert L., Harter P., Hettle R., Lorusso D., Maenpaa J., Marth C., Matsumoto K., Ouwens M., Poveda A., Raspagliesi F., Rhodes K., Rubio Perez M. J., Shapira-Frommer R., Shikama A., Sikorska M., Moore K., and DiSilvestro P.

Abstract

Background: In the absence of randomised head-to-head trials, we conducted a population-adjusted indirect treatment comparison (PA-ITC) of phase III trial data to evaluate the relative efficacy and safety of maintenance olaparib and bevacizumab alone and in combination in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation (BRCAm). Methods: An unanchored PA-ITC was performed on investigator-assessed progression-free survival (PFS) data. Individual patient data from SOLO1 (olaparib versus placebo) and from BRCA-mutated patients in PAOLA-1/ENGOT-ov25 (olaparib plus bevacizumab versus placebo plus bevacizumab) were pooled. Each arm of PAOLA-1 was weighted so that key baseline patient characteristics were similar to the SOLO1 cohort. Analyses were performed in patients with complete baseline data. Weighted Cox regression analysis was used to estimate the comparative efficacy of different maintenance therapy strategies, supplemented by weighted Kaplan–Meier analyses. Results: Data from SOLO1 patients (olaparib, n = 254; placebo, n = 126) were compared with data from BRCA-mutated PAOLA-1 patients (olaparib plus bevacizumab, n = 151; placebo plus bevacizumab, n = 71). Adding bevacizumab to olaparib was associated with a numerical improvement in PFS compared with olaparib alone (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.45–1.09). Statistically significant improvements in PFS were seen with olaparib alone versus placebo plus bevacizumab (HR 0.48; 95% CI 0.30–0.75), olaparib plus bevacizumab versus placebo (0.23; 0.14–0.34), and placebo plus bevacizumab versus placebo (0.65; 0.43–0.95). Conclusions: Results of this hypothesis-generating PA-ITC analysis support the use of maintenance olaparib alone or with bevacizumab in patients with newly diagnosed, advanced ovarian cancer and a BRCAm.

Published
2021

7. 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

Author

Friedlander, M, Moore, K, Colombo, N, Scambia, G, Kim, B, Oaknin, A, Lisyanskaya, A, Sonke, G, Gourley, C, Banerjee, S, Oza, A, Gonzalez-Martin, A, Aghajanian, C, Bradley, W, Liu, J, Mathews, C, Selle, F, Lortholary, A, Lowe, E, Hettle, R, Flood, E, Parkhomenko, E, Disilvestro, P, Friedlander M., Moore K. N., Colombo N., Scambia G., Kim B. -G., Oaknin A., Lisyanskaya A., Sonke G. S., Gourley C., Banerjee S., Oza A., Gonzalez-Martin A., Aghajanian C., Bradley W. H., Liu J., Mathews C., Selle F., Lortholary A., Lowe E. S., Hettle R., Flood E., Parkhomenko E., DiSilvestro P., Friedlander, M, Moore, K, Colombo, N, Scambia, G, Kim, B, Oaknin, A, Lisyanskaya, A, Sonke, G, Gourley, C, Banerjee, S, Oza, A, Gonzalez-Martin, A, Aghajanian, C, Bradley, W, Liu, J, Mathews, C, Selle, F, Lortholary, A, Lowe, E, Hettle, R, Flood, E, Parkhomenko, E, Disilvestro, P, Friedlander M., Moore K. N., Colombo N., Scambia G., Kim B. -G., Oaknin A., Lisyanskaya A., Sonke G. S., Gourley C., Banerjee S., Oza A., Gonzalez-Martin A., Aghajanian C., Bradley W. H., Liu J., Mathews C., Selle F., Lortholary A., Lowe E. S., Hettle R., Flood E., Parkhomenko E., and DiSilvestro P.

Abstract

Background: In the phase 3 SOLO1 trial, maintenance olaparib provided a significant progression-free survival benefit versus placebo in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation in response after platinum-based chemotherapy. We analysed health-related quality of life (HRQOL) and patient-centred outcomes in SOLO1, and the effect of radiological disease progression on health status. Methods: SOLO1 is a randomised, double-blind, international trial done in 118 centres and 15 countries. Eligible patients were aged 18 years or older; had an Eastern Cooperative Oncology Group performance status score of 0–1; had newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with a BRCA mutation; and were in clinical complete or partial response to platinum-based chemotherapy. Patients were randomly assigned (2:1) to either 300 mg olaparib tablets or placebo twice per day using an interactive voice and web response system and were treated for up to 2 years. Treatment assignment was masked for patients and for clinicians giving the interventions, and those collecting and analysing the data. Randomisation was stratified by response to platinum-based chemotherapy (clinical complete or partial response). HRQOL was a secondary endpoint and the prespecified primary HRQOL endpoint was the change from baseline in the Functional Assessment of Cancer Therapy–Ovarian Cancer Trial Outcome Index (TOI) score for the first 24 months. TOI scores range from 0 to 100 (higher scores indicated better HRQOL), with a clinically meaningful difference defined as a difference of at least 10 points. Prespecified exploratory endpoints were quality-adjusted progression-free survival and time without significant symptoms of toxicity (TWiST). HRQOL endpoints were analysed in all randomly assigned patients. The trial is ongoing but closed to new participants. This trial is registered with ClinicalTrials.go

Published
2021

10. Assessing the long-term effectiveness of cladribine vs. placebo in the relapsing-remitting multiple sclerosis CLARITY randomized controlled trial and CLARITY extension using treatment switching adjustment methods

Author

Bell Gorrod, H., Latimer, N.R., Damian, D., Hettle, R., Harty, G.T., and Wong, S.L.

Abstract

Objectives: Treatment switching adjustment methods are often used to adjust for switching in oncology randomized controlled trials (RCTs). In this exploratory analysis, we apply these methods to adjust for treatment changes in the setting of an RCT followed by an extension study in relapsing-remitting multiple sclerosis.\ud \ud Methods: The CLARITY trial evaluated cladribine tablets versus placebo over 96 weeks. In the 96-week CLARITY Extension, patients who received placebo in CLARITY received cladribine tablets; patients who received cladribine tablets in CLARITY were re-randomized to placebo or cladribine tablets. Endpoints were time to first qualifying relapse (FQR) and time to 3- and 6-month confirmed disability progression (3mCDP, 6mCDP). We aimed to compare the effectiveness of cladribine tablets to placebo over CLARITY and the extension. The rank preserving structural failure time model (RPSFTM) and Iterative Parameter Estimation (IPE) were used to estimate what would have happened if patients had received placebo in CLARITY and the extension, versus patients that received cladribine tablets and switched to placebo. To gauge whether treatment effect waned after the 96 weeks of CLARITY, we compared hazard ratios (HRs) from the adjustment analysis with HRs from CLARITY.\ud \ud Results: The RPSFTM resulted in a HR of 0.48 (95% confidence interval [CI] 0.36-0.62) for FQR, 0.62 (95% CI 0.46-0.84) for 3mCDP, and 0.62 (95% CI 0.44-0.88) for 6mCDP. IPE algorithm results were similar. CLARITY HRs were 0.44 (95% CI 0.34-0.58), 0.60 (95% CI 0.41-0.87) and 0.58 (95% CI 0.40-0.83) for FQR, 3mCDP and 6mCDP respectively.\ud \ud Conclusions: Treatment switching adjustment methods are applicable in non-oncology settings. Adjusted CLARITY plus CLARITY Extension HRs were similar to the CLARITY HRs, demonstrating significant treatment benefits associated with cladribine tablets versus placebo.

Published
2020

13. Cost-effectiveness analysis of olaparib as a maintenance monotherapy for patients with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation: A United States payer perspective

Author

Muston, D.R.G., primary, Monberg, M.J., additional, McLaurin, K., additional, Sackeyfio, A., additional, Hettle, R., additional, Signorovitch, J., additional, Swallow, E., additional, Gao, W., additional, Zhang, S., additional, Kalemaj, I., additional, and Moore, K.N., additional

Published
2020
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18. Patient-centred outcomes with maintenance olaparib in newly diagnosed patients with advanced ovarian cancer (OC) and a BRCA mutation in the phase III SOLO1 trial to support the clinical benefit of prolongation of progression-free survival (PFS)

Author

Friedlander, M.L., primary, Moore, K.N., additional, Colombo, N., additional, Scambia, G., additional, Kim, B.-G., additional, Oaknin, A., additional, Lisyanskaya, A., additional, Floquet, A., additional, Leary, A., additional, Sonke, G.S., additional, Gourley, C., additional, Banerjee, S., additional, Oza, A., additional, González-Martín, A., additional, Aghajanian, C., additional, Bradley, W., additional, Lowe, E., additional, Hettle, R., additional, Flood, E., additional, and Disilvestro, P., additional

Published
2019
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21. Patient-centred outcomes with maintenance olaparib in newly diagnosed patients with advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) in the phase III SOLO1 trial to support the clinical benefit of prolongation of progression-free survival (PFS)

Author

Friedlander, M.L., primary, Moore, K., additional, Colombo, N., additional, Scambia, G., additional, Kim, B.-G., additional, Oaknin, A., additional, Lisyanskaya, A., additional, Floquet, A., additional, Leary, A., additional, Sonke, G.S., additional, Gourley, C., additional, Banerjee, S., additional, Oza, A., additional, González-Martín, A., additional, Aghajanian, C., additional, Bradley, W., additional, Lowe, E., additional, Hettle, R., additional, Flood, E., additional, and DiSilvestro, P., additional

Published
2019
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28. A MATCHING‐ADJUSTED INDIRECT COMPARISON OF THE EFFICACY AND SAFETY OF ACALABRUTINIB VERSUS ZANUBRUTINIB IN RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA.

Author

Ghia, P., Skarbnik, A., Miranda, M., Yong, A. S., Roos, J., Hettle, R., Palazuelos‐Munoz, S., Shetty, V., and Kittai, A.

Subjects
CHRONIC lymphocytic leukemia, BRUTON tyrosine kinase
Abstract

B Introduction: b Next-generation Bruton tyrosine kinase inhibitors (BTKis) acalabrutinib (acala) and zanubrutinib (zanu) were compared with the standard of care BTKi ibrutinib in relapsed/refractory chronic lymphocytic leukemia (RR CLL) in the head-to-head randomized clinical trials (RCTs) ELEVATE-RR and ALPINE, respectively. A safety analysis assessed odds ratios (ORs) of adverse events (AEs) in treated patients with baseline data (acala, n = 148; zanu, n = 324). An efficacy analysis assessed investigator-assessed PFS (INV PFS) in randomized patients with baseline data (acala, n = 149; zanu, n = 327). [Extracted from the article]

Published
2023
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34. Cost Effectiveness of Ribociclib Plus Letrozole Versus Palbociclib Plus Letrozole for The Treatment of Post-Menopausal Women with Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Advanced or Metastatic Breast Cancer from A US Private Third-Party Payer Perspective

Author

Suri, G, primary, Mistry, R, additional, Young, KC, additional, Hettle, R, additional, May, JR, additional, Brixner, D, additional, Oderda, G, additional, Biskupiak, J, additional, Tang, D, additional, Bhattacharyya, D, additional, Bhattacharyya, S, additional, Mishra, D, additional, and Dalal, A, additional

Published
2017
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38. Budget Impact of Ribociclib Plus Letrozole For The Treatment of Post-Menopausal Women With Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2- Negative (HER2-) Advanced or Metastatic Breast Cancer From A US Private Third-Party Payer Perspective

Author

Mistry, R, primary, Suri, G, additional, Young, KC, additional, Hettle, R, additional, May, JR, additional, Brixner, D, additional, Oderda, G, additional, Biskupiak, J, additional, Tang, D, additional, Bhattacharyya, D, additional, Bhattacharyya, S, additional, Mishra, D, additional, and Dalal, A, additional

Published
2017
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40. 224O - Patient-centred outcomes with maintenance olaparib in newly diagnosed patients with advanced ovarian cancer (OC) and a BRCA mutation in the phase III SOLO1 trial to support the clinical benefit of prolongation of progression-free survival (PFS)

Author

Friedlander, M.L., Moore, K.N., Colombo, N., Scambia, G., Kim, B.-G., Oaknin, A., Lisyanskaya, A., Floquet, A., Leary, A., Sonke, G.S., Gourley, C., Banerjee, S., Oza, A., González-Martín, A., Aghajanian, C., Bradley, W., Lowe, E., Hettle, R., Flood, E., and Disilvestro, P.

Published
2019
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43. 996PD - Patient-centred outcomes with maintenance olaparib in newly diagnosed patients with advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) in the phase III SOLO1 trial to support the clinical benefit of prolongation of progression-free survival (PFS)

Author

Friedlander, M.L., Moore, K., Colombo, N., Scambia, G., Kim, B.-G., Oaknin, A., Lisyanskaya, A., Floquet, A., Leary, A., Sonke, G.S., Gourley, C., Banerjee, S., Oza, A., González-Martín, A., Aghajanian, C., Bradley, W., Lowe, E., Hettle, R., Flood, E., and DiSilvestro, P.

Published
2019
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48. PCN133 - Cost Effectiveness of Ribociclib Plus Letrozole Versus Palbociclib Plus Letrozole for The Treatment of Post-Menopausal Women with Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Advanced or Metastatic Breast Cancer from A US Private Third-Party Payer Perspective

Author

Suri, G, Mistry, R, Young, KC, Hettle, R, May, JR, Brixner, D, Oderda, G, Biskupiak, J, Tang, D, Bhattacharyya, D, Bhattacharyya, S, Mishra, D, and Dalal, A

Published
2017
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