Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial

F. Trillsch, Sven Mahner, F. Hilpert, L. Davies, E. García-Martínez, G. Kristensen, A. Savarese, P. Vuylsteke, M. Los, F. Zagouri, L. Gladieff, J. Sehouli, C. Khoon Lee, V. Gebski, E. Pujade-Lauraine

Research output: Contribution to journalArticle

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Abstract

Background: Progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PROs) were significantly improved by adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) in the phase III AURELIA trial. We explored treatment outcomes according to primary platinum resistance (PPR) versus secondary platinum resistance (SPR). Patients and methods: Patients were categorized as PPR (disease progression <6 months after completing first-line platinum therapy) or SPR (progression ≥6 months after first platinum but <6 months after second). The exploratory Cox and logistic regression analyses correlated PFS, ORR, overall survival (OS), and PROs with the time to development of platinum resistance. Results: Baseline characteristics were similar in patients with PPR (n = 262; 73%) and SPR (n = 99; 27%), although ascites were more common in the PPR subgroup. In bevacizumab-treated patients (n = 179), SPR was associated with improved PFS (median 10.2 versus 5.6 months in PPR patients; P < 0.001) and OS (median 22.2 versus 13.7 months, respectively; P < 0.001) but not PROs (22% versus 22% with improved abdominal/gastrointestinal symptoms at week 8/9). In multivariate analyses, SPR remained an independent prognostic factor for better PFS [adjusted hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.25-0.67; P < 0.001] and OS (HR 0.49, 95% CI 0.30-0.80; P = 0.005) in bevacizumab-treated patients, but was not statistically significant for either end point in the chemotherapy-alone subgroup. The magnitude of PFS benefit from bevacizumab appeared greater in SPR than PPR patients (HR 0.30 versus 0.55, respectively; interaction P = 0.07) with a similar direction of effect for OS (interaction P = 0.18). Conclusions: In bevacizumab-treated patients, PFS and OS were more favorable in SPR than PPR patients with equally improved PROs. The PFS and OS benefit from combining bevacizumab with chemotherapy was more pronounced in SPR than PPR PROC. PPR versus SPR should be a stratification factor in future trials evaluating anti-angiogenic therapy for PROC.

Original languageEnglish
Article numbermdw236
Pages (from-to)1733-1739
Number of pages7
JournalAnnals of Oncology
Volume27
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

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Platinum
Ovarian Neoplasms
Disease-Free Survival
Therapeutics
Bevacizumab
Survival
Drug Therapy
Confidence Intervals

Keywords

  • Anti-angiogenic therapy
  • Bevacizumab
  • Platinum resistance
  • Prognostic factors
  • Recurrent ovarian cancer
  • Response rates

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Trillsch, F., Mahner, S., Hilpert, F., Davies, L., García-Martínez, E., Kristensen, G., ... Pujade-Lauraine, E. (2016). Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial. Annals of Oncology, 27(9), 1733-1739. [mdw236]. https://doi.org/10.1093/annonc/mdw236

Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial. / Trillsch, F.; Mahner, Sven; Hilpert, F.; Davies, L.; García-Martínez, E.; Kristensen, G.; Savarese, A.; Vuylsteke, P.; Los, M.; Zagouri, F.; Gladieff, L.; Sehouli, J.; Khoon Lee, C.; Gebski, V.; Pujade-Lauraine, E.

In: Annals of Oncology, Vol. 27, No. 9, mdw236, 01.09.2016, p. 1733-1739.

Research output: Contribution to journalArticle

Trillsch, F, Mahner, S, Hilpert, F, Davies, L, García-Martínez, E, Kristensen, G, Savarese, A, Vuylsteke, P, Los, M, Zagouri, F, Gladieff, L, Sehouli, J, Khoon Lee, C, Gebski, V & Pujade-Lauraine, E 2016, 'Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial', Annals of Oncology, vol. 27, no. 9, mdw236, pp. 1733-1739. https://doi.org/10.1093/annonc/mdw236
Trillsch, F. ; Mahner, Sven ; Hilpert, F. ; Davies, L. ; García-Martínez, E. ; Kristensen, G. ; Savarese, A. ; Vuylsteke, P. ; Los, M. ; Zagouri, F. ; Gladieff, L. ; Sehouli, J. ; Khoon Lee, C. ; Gebski, V. ; Pujade-Lauraine, E. / Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial. In: Annals of Oncology. 2016 ; Vol. 27, No. 9. pp. 1733-1739.
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title = "Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial",
abstract = "Background: Progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PROs) were significantly improved by adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) in the phase III AURELIA trial. We explored treatment outcomes according to primary platinum resistance (PPR) versus secondary platinum resistance (SPR). Patients and methods: Patients were categorized as PPR (disease progression <6 months after completing first-line platinum therapy) or SPR (progression ≥6 months after first platinum but <6 months after second). The exploratory Cox and logistic regression analyses correlated PFS, ORR, overall survival (OS), and PROs with the time to development of platinum resistance. Results: Baseline characteristics were similar in patients with PPR (n = 262; 73{\%}) and SPR (n = 99; 27{\%}), although ascites were more common in the PPR subgroup. In bevacizumab-treated patients (n = 179), SPR was associated with improved PFS (median 10.2 versus 5.6 months in PPR patients; P < 0.001) and OS (median 22.2 versus 13.7 months, respectively; P < 0.001) but not PROs (22{\%} versus 22{\%} with improved abdominal/gastrointestinal symptoms at week 8/9). In multivariate analyses, SPR remained an independent prognostic factor for better PFS [adjusted hazard ratio (HR) 0.41, 95{\%} confidence interval (CI) 0.25-0.67; P < 0.001] and OS (HR 0.49, 95{\%} CI 0.30-0.80; P = 0.005) in bevacizumab-treated patients, but was not statistically significant for either end point in the chemotherapy-alone subgroup. The magnitude of PFS benefit from bevacizumab appeared greater in SPR than PPR patients (HR 0.30 versus 0.55, respectively; interaction P = 0.07) with a similar direction of effect for OS (interaction P = 0.18). Conclusions: In bevacizumab-treated patients, PFS and OS were more favorable in SPR than PPR patients with equally improved PROs. The PFS and OS benefit from combining bevacizumab with chemotherapy was more pronounced in SPR than PPR PROC. PPR versus SPR should be a stratification factor in future trials evaluating anti-angiogenic therapy for PROC.",
keywords = "Anti-angiogenic therapy, Bevacizumab, Platinum resistance, Prognostic factors, Recurrent ovarian cancer, Response rates",
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T1 - Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial

AU - Trillsch, F.

AU - Mahner, Sven

AU - Hilpert, F.

AU - Davies, L.

AU - García-Martínez, E.

AU - Kristensen, G.

AU - Savarese, A.

AU - Vuylsteke, P.

AU - Los, M.

AU - Zagouri, F.

AU - Gladieff, L.

AU - Sehouli, J.

AU - Khoon Lee, C.

AU - Gebski, V.

AU - Pujade-Lauraine, E.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background: Progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PROs) were significantly improved by adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) in the phase III AURELIA trial. We explored treatment outcomes according to primary platinum resistance (PPR) versus secondary platinum resistance (SPR). Patients and methods: Patients were categorized as PPR (disease progression <6 months after completing first-line platinum therapy) or SPR (progression ≥6 months after first platinum but <6 months after second). The exploratory Cox and logistic regression analyses correlated PFS, ORR, overall survival (OS), and PROs with the time to development of platinum resistance. Results: Baseline characteristics were similar in patients with PPR (n = 262; 73%) and SPR (n = 99; 27%), although ascites were more common in the PPR subgroup. In bevacizumab-treated patients (n = 179), SPR was associated with improved PFS (median 10.2 versus 5.6 months in PPR patients; P < 0.001) and OS (median 22.2 versus 13.7 months, respectively; P < 0.001) but not PROs (22% versus 22% with improved abdominal/gastrointestinal symptoms at week 8/9). In multivariate analyses, SPR remained an independent prognostic factor for better PFS [adjusted hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.25-0.67; P < 0.001] and OS (HR 0.49, 95% CI 0.30-0.80; P = 0.005) in bevacizumab-treated patients, but was not statistically significant for either end point in the chemotherapy-alone subgroup. The magnitude of PFS benefit from bevacizumab appeared greater in SPR than PPR patients (HR 0.30 versus 0.55, respectively; interaction P = 0.07) with a similar direction of effect for OS (interaction P = 0.18). Conclusions: In bevacizumab-treated patients, PFS and OS were more favorable in SPR than PPR patients with equally improved PROs. The PFS and OS benefit from combining bevacizumab with chemotherapy was more pronounced in SPR than PPR PROC. PPR versus SPR should be a stratification factor in future trials evaluating anti-angiogenic therapy for PROC.

AB - Background: Progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PROs) were significantly improved by adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) in the phase III AURELIA trial. We explored treatment outcomes according to primary platinum resistance (PPR) versus secondary platinum resistance (SPR). Patients and methods: Patients were categorized as PPR (disease progression <6 months after completing first-line platinum therapy) or SPR (progression ≥6 months after first platinum but <6 months after second). The exploratory Cox and logistic regression analyses correlated PFS, ORR, overall survival (OS), and PROs with the time to development of platinum resistance. Results: Baseline characteristics were similar in patients with PPR (n = 262; 73%) and SPR (n = 99; 27%), although ascites were more common in the PPR subgroup. In bevacizumab-treated patients (n = 179), SPR was associated with improved PFS (median 10.2 versus 5.6 months in PPR patients; P < 0.001) and OS (median 22.2 versus 13.7 months, respectively; P < 0.001) but not PROs (22% versus 22% with improved abdominal/gastrointestinal symptoms at week 8/9). In multivariate analyses, SPR remained an independent prognostic factor for better PFS [adjusted hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.25-0.67; P < 0.001] and OS (HR 0.49, 95% CI 0.30-0.80; P = 0.005) in bevacizumab-treated patients, but was not statistically significant for either end point in the chemotherapy-alone subgroup. The magnitude of PFS benefit from bevacizumab appeared greater in SPR than PPR patients (HR 0.30 versus 0.55, respectively; interaction P = 0.07) with a similar direction of effect for OS (interaction P = 0.18). Conclusions: In bevacizumab-treated patients, PFS and OS were more favorable in SPR than PPR patients with equally improved PROs. The PFS and OS benefit from combining bevacizumab with chemotherapy was more pronounced in SPR than PPR PROC. PPR versus SPR should be a stratification factor in future trials evaluating anti-angiogenic therapy for PROC.

KW - Anti-angiogenic therapy

KW - Bevacizumab

KW - Platinum resistance

KW - Prognostic factors

KW - Recurrent ovarian cancer

KW - Response rates

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DO - 10.1093/annonc/mdw236

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VL - 27

SP - 1733

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JO - Annals of Oncology

JF - Annals of Oncology

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