European Journal of Cancer (2014) xxx, xxx– xxx
Available at www.sciencedirect.com
ScienceDirect journal homepage: www.ejcancer.com
Letter to the Editor
Updated results from OCTAVIA (front-line bevacizumab, carboplatin and weekly paclitaxel therapy for ovarian cancer) Antonio Gonzalez-Martin a,⇑, Laurence Gladieff b, Bengt Tholander c, Daniel Stroyakovsky d, Martin Gore e, Giovanni Scambia f, Ana Oaknin g, Vesna Sneller h, Ulrich Freudensprung h, Sandro Pignata i, on behalf of the OCTAVIA investigators a
GEICO and MD Anderson Cancer Center Spain, Madrid, Spain GINECO and Institut Claudius Regaud, Toulouse, France c NSGO and Uppsala University Hospital, Uppsala, Sweden d Moscow Oncology Hospital No. 62, Moscow, Russian Federation e The Royal Marsden Hospital, London, UK f Universita` Cattolica Roma, Rome, Italy g Vall d’Hebron University Hospital, Barcelona, Spain h F. Hoffmann-La Roche Ltd, Basel, Switzerland i MITO and Department of Urology and Gynecology, Istituto Nazionale Tumori Fondazione G. Pascale, IRCCS, Naples, Italy b
Received 15 November 2013; accepted 1 December 2013
Sir, Recently in this journal, we reported the primary efficacy and safety results from the single-arm OCTAVIA study evaluating the combination of bevacizumab, carboplatin and weekly paclitaxel as front-line treatment for ovarian cancer [1]. At the primary PFS analysis, median progression-free survival (PFS) was 23.7 months (90% confidence interval [CI] 19.9–26.4 months; 95% CI 19.8–26.4 months; PFS events in 52% of patients) in the overall population and 18.1 months (95% CI 16.0– 19.6 months; PFS events in 69% of patients) in the subgroup at high risk of progression (original ICON7 definition [2]). ⇑ Corresponding author: Tel.: +34 917878605; fax: +34 917680687.
E-mail address: [email protected] (A. Gonzalez-Martin).
Here we report the prespecified analysis of overall survival (OS; a secondary end-point) and updated PFS results 1 year after the primary PFS analysis. At the data cutoff for this updated, end-of-study analysis (29th July 2013; median follow-up 35.7 months), 105 of the 189 treated patients (56%) had experienced a PFS event, including 32 deaths (17%). This represents six additional PFS events and 13 deaths, all from disease progression, since the primary PFS analysis. In both the overall and the high-risk populations, median PFS was consistent with results from the primary PFS analysis (Table 1). In some subgroups, the PFS results are immature with PFS events in fewer than 50% of patients. For assessment of the secondary endpoint, OS, the very limited number of events (17% of patients) at the planned end-of-study analysis means
0959-8049/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejca.2013.12.001
Please cite this article in press as: Gonzalez-Martin A. et al., Updated results from OCTAVIA (front-line bevacizumab, carboplatin and weekly paclitaxel therapy for ovarian cancer), Eur J Cancer (2014), http://dx.doi.org/10.1016/j.ejca.2013.12.001
2
A. Gonzalez-Martin et al. / European Journal of Cancer xxx (2014) xxx–xxx
Table 1 Summary of PFS at end of study. Subgroup
No. of events/no. of patients (%)
Median PFS, months (95% CI)
All patients Age, years
0–61 >1
22/60 (37) 17/32 (53) 50/69 (72)
36.4 (34.9–36.4) 26.4 (17.5–NR) 18.1 (16.0–22.5)
High risk of progressionc
No Yes
49/112 (44) 56/77 (73)
36.4 (27.2–36.4) 17.8 (14.9–19.5)
CI = confidence interval; ECOG PS = Eastern Cooperative Oncology Group performance status; FIGO = International Federation of Gynaecology and Obstetrics; NR = not reached; PFS = progression-free survival. a Missing in one patient. b No debulking in nine patients, optimal unknown in 19 patients. c FIGO stage IV/FIGO stage III and >1.0 cm residual disease after debulking surgery or no debulking surgery (modified ICON7 definition) [3].
that OS results are not mature. One- and 2-year OS rates are 97.8% (95% CI 95.7–99.9%) and 92.3% (95% CI 88.4–96.2%), respectively. Of note, there were no additional adverse events. In summary, the regimen of bevacizumab, weekly paclitaxel and 3-weekly carboplatin evaluated in OCTAVIA is active and tolerable and we believe it can be considered in patients for whom weekly paclitaxel is preferred to the 3-weekly schedule. Conflict of interest statement Antonio Gonzalez-Martin has acted as a Consultant/ Advisor for PharmaMar, Roche and Janssen. Laurence Gladieff, Martin Gore and Sandro Pignata have received honoraria from Roche. Martin Gore and Sandro Pignata have acted as Consultants/Advisors for Roche. Vesna Sneller and Ulrich Freudensprung are employees
of F. Hoffmann-La Roche Ltd. Sandro Pignata has received research funding from Roche.
References [1] Gonzalez-Martin A, Gladieff L, Tholander B, Stroyakovsky D, Gore M, Scambia G, et al. on behalf of the OCTAVIA Investigators. Efficacy and safety results from OCTAVIA, a single-arm phase II study evaluating front-line bevacizumab, carboplatin and weekly paclitaxel for ovarian cancer. Eur J Cancer 2013;49(18):3831–8. [2] Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, et al, ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 2011;365:2484–96. [3] Oza AM, Perren TJ, Swart AM, Schro¨der W, Pujade-Lauraine E, Havsteen H, et al. ICON7: final overall survival results in the GCIG phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer. Eur J Cancer 2013;49(Suppl. 3):S4 (abstract LBA6).
Please cite this article in press as: Gonzalez-Martin A. et al., Updated results from OCTAVIA (front-line bevacizumab, carboplatin and weekly paclitaxel therapy for ovarian cancer), Eur J Cancer (2014), http://dx.doi.org/10.1016/j.ejca.2013.12.001
Available at www.sciencedirect.com
ScienceDirect journal homepage: www.ejcancer.com
Letter to the Editor
Updated results from OCTAVIA (front-line bevacizumab, carboplatin and weekly paclitaxel therapy for ovarian cancer) Antonio Gonzalez-Martin a,⇑, Laurence Gladieff b, Bengt Tholander c, Daniel Stroyakovsky d, Martin Gore e, Giovanni Scambia f, Ana Oaknin g, Vesna Sneller h, Ulrich Freudensprung h, Sandro Pignata i, on behalf of the OCTAVIA investigators a
GEICO and MD Anderson Cancer Center Spain, Madrid, Spain GINECO and Institut Claudius Regaud, Toulouse, France c NSGO and Uppsala University Hospital, Uppsala, Sweden d Moscow Oncology Hospital No. 62, Moscow, Russian Federation e The Royal Marsden Hospital, London, UK f Universita` Cattolica Roma, Rome, Italy g Vall d’Hebron University Hospital, Barcelona, Spain h F. Hoffmann-La Roche Ltd, Basel, Switzerland i MITO and Department of Urology and Gynecology, Istituto Nazionale Tumori Fondazione G. Pascale, IRCCS, Naples, Italy b
Received 15 November 2013; accepted 1 December 2013
Sir, Recently in this journal, we reported the primary efficacy and safety results from the single-arm OCTAVIA study evaluating the combination of bevacizumab, carboplatin and weekly paclitaxel as front-line treatment for ovarian cancer [1]. At the primary PFS analysis, median progression-free survival (PFS) was 23.7 months (90% confidence interval [CI] 19.9–26.4 months; 95% CI 19.8–26.4 months; PFS events in 52% of patients) in the overall population and 18.1 months (95% CI 16.0– 19.6 months; PFS events in 69% of patients) in the subgroup at high risk of progression (original ICON7 definition [2]). ⇑ Corresponding author: Tel.: +34 917878605; fax: +34 917680687.
E-mail address: [email protected] (A. Gonzalez-Martin).
Here we report the prespecified analysis of overall survival (OS; a secondary end-point) and updated PFS results 1 year after the primary PFS analysis. At the data cutoff for this updated, end-of-study analysis (29th July 2013; median follow-up 35.7 months), 105 of the 189 treated patients (56%) had experienced a PFS event, including 32 deaths (17%). This represents six additional PFS events and 13 deaths, all from disease progression, since the primary PFS analysis. In both the overall and the high-risk populations, median PFS was consistent with results from the primary PFS analysis (Table 1). In some subgroups, the PFS results are immature with PFS events in fewer than 50% of patients. For assessment of the secondary endpoint, OS, the very limited number of events (17% of patients) at the planned end-of-study analysis means
0959-8049/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejca.2013.12.001
Please cite this article in press as: Gonzalez-Martin A. et al., Updated results from OCTAVIA (front-line bevacizumab, carboplatin and weekly paclitaxel therapy for ovarian cancer), Eur J Cancer (2014), http://dx.doi.org/10.1016/j.ejca.2013.12.001
2
A. Gonzalez-Martin et al. / European Journal of Cancer xxx (2014) xxx–xxx
Table 1 Summary of PFS at end of study. Subgroup
No. of events/no. of patients (%)
Median PFS, months (95% CI)
All patients Age, years
0–61 >1
22/60 (37) 17/32 (53) 50/69 (72)
36.4 (34.9–36.4) 26.4 (17.5–NR) 18.1 (16.0–22.5)
High risk of progressionc
No Yes
49/112 (44) 56/77 (73)
36.4 (27.2–36.4) 17.8 (14.9–19.5)
CI = confidence interval; ECOG PS = Eastern Cooperative Oncology Group performance status; FIGO = International Federation of Gynaecology and Obstetrics; NR = not reached; PFS = progression-free survival. a Missing in one patient. b No debulking in nine patients, optimal unknown in 19 patients. c FIGO stage IV/FIGO stage III and >1.0 cm residual disease after debulking surgery or no debulking surgery (modified ICON7 definition) [3].
that OS results are not mature. One- and 2-year OS rates are 97.8% (95% CI 95.7–99.9%) and 92.3% (95% CI 88.4–96.2%), respectively. Of note, there were no additional adverse events. In summary, the regimen of bevacizumab, weekly paclitaxel and 3-weekly carboplatin evaluated in OCTAVIA is active and tolerable and we believe it can be considered in patients for whom weekly paclitaxel is preferred to the 3-weekly schedule. Conflict of interest statement Antonio Gonzalez-Martin has acted as a Consultant/ Advisor for PharmaMar, Roche and Janssen. Laurence Gladieff, Martin Gore and Sandro Pignata have received honoraria from Roche. Martin Gore and Sandro Pignata have acted as Consultants/Advisors for Roche. Vesna Sneller and Ulrich Freudensprung are employees
of F. Hoffmann-La Roche Ltd. Sandro Pignata has received research funding from Roche.
References [1] Gonzalez-Martin A, Gladieff L, Tholander B, Stroyakovsky D, Gore M, Scambia G, et al. on behalf of the OCTAVIA Investigators. Efficacy and safety results from OCTAVIA, a single-arm phase II study evaluating front-line bevacizumab, carboplatin and weekly paclitaxel for ovarian cancer. Eur J Cancer 2013;49(18):3831–8. [2] Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, et al, ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 2011;365:2484–96. [3] Oza AM, Perren TJ, Swart AM, Schro¨der W, Pujade-Lauraine E, Havsteen H, et al. ICON7: final overall survival results in the GCIG phase III randomized trial of bevacizumab in women with newly diagnosed ovarian cancer. Eur J Cancer 2013;49(Suppl. 3):S4 (abstract LBA6).
Please cite this article in press as: Gonzalez-Martin A. et al., Updated results from OCTAVIA (front-line bevacizumab, carboplatin and weekly paclitaxel therapy for ovarian cancer), Eur J Cancer (2014), http://dx.doi.org/10.1016/j.ejca.2013.12.001
