Contributions
Abstract: P686
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: A higher incidence rate (IR) of malignancies including female breast cancer was observed in ocrelizumab (OCR)-treated patients compared with pooled interferon beta-1a (IFN β-1a) or placebo (PBO)-treated patients.
Objective: To provide an update on the IR of malignancies in the OCR clinical trial programme, in the context of data from other multiple sclerosis (MS) trials (PBO only), epidemiological data sources (MS registries) and the general population (National Cancer Institute [NCI] Surveillance, Epidemiology, and End Results [SEER]).
Methods: Crude IR of first malignancies were calculated across the OCR MS development programme (Phase II: NCT00676715; OPERA I: NCT01247324; OPERA II: NCT01412333; ORATORIO: NCT01194570) in a primary analysis (clinical cut-off dates 22 January-24 July 2015) and updated as of 20 January 2016 and 17 February 2017. Results are contextualised using a meta-analysis of published data of PBO-treated patients from up to 10 MS clinical studies (PBO-MSCS), and data derived from other published MS-specific epidemiological sources (Danish, Swedish or Canadian British Columbia MS registries [DMSR, SMSR, CBCMSR]). Age- and sex-standardised IR of malignancies from the OCR MS programme and the SEER database are provided.
Results: IRs per 100 patient-years (95% confidence interval) for all malignancies and breast cancer in the primary analysis for OCR were 0.43 (0.26-0.66) and 0.26 (0.11-0.54); for the January 2016 update, IRs were 0.44 (0.29-0.65) and 0.23 (0.10-0.46). As of 17 February 2017, the IR of all malignancies was 0.45 (0.32-0.63) for OCR, 0.50 (0.36-0.67) for PBO-MSCS and 0.67 (0.63-0.71) for the DMSR. The rate of female breast cancer was 0.19 (0.09-0.37) for OCR, 0.16 (0.06-0.32) for PBO-MSCS, 0.21 (0.18-0.23) for DMSR, 0.20 (0.18-0.22) for SMSR and 0.14 (0.11-0.16) for CBCMSR. The standardised IR for malignancies excluding non-melanoma skin cancer was 0.24 (0.15-0.41) for OCR and 0.27 (0.27-0.27) for SEER, and for female breast cancer was 0.19 (0.08-0.42) for OCR and 0.12 (0.12-0.13) for SEER.
Conclusions: With additional exposure, the rate of malignancies in OCR-treated patients fall within the range of PBO data from clinical trials in MS and epidemiological data. It is noted that indirect comparisons have limitations, and ongoing data collection through post-approval safety studies are required to characterize the potential risk of malignancies, including breast cancer.
Disclosure: Data provided by LASER; sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
S.L. Hauser serves on the board of trustees for Neurona and on scientific advisory boards for Annexon, Symbiotix and Bionure; he has also received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd for CD20-related meetings and presentations.
L. Kappos's institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos's activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer HealthCare Pharmaceuticals, CLC Behring, Genentech, Inc., GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Ono Pharma, Pfizer, Receptos,
F. Hoffmann-La Roche Ltd, Sanofi, Santhera, Siemens, Teva, UCB and XenoPort; license fees for Neurostatus products; and research grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto Foundation, the Novartis Research Foundation and the Roche Research Foundation.
X. Montalban has received speaking honoraria and travel expense reimbursement for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Actelion, Almirall, Bayer, Biogen, Genzyme, Merck, Novartis, Octapharma, Receptos, F. Hoffmann-La Roche Ltd, Sanofi, Teva and Trophos.
P. Chin is an employee of Genentech, Inc. and shareholder of F. Hoffmann-La Roche Ltd.
M.C. Green is an employee of Genentech Inc.
H. Koendgen is an employee and shareholder of F. Hoffmann-La Roche Ltd.
C. Li is an employee of F. Hoffmann-La Roche Ltd.
B. Shi is an employee of F. Hoffmann-La Roche Ltd.
D. Wormser is an employee and shareholder of F. Hoffmann-La Roche Ltd.
J.S. Wolinsky has served on advisory boards, data monitoring or steering committees, has consulting agreements, or received speaker honoraria from the following entities: AbbVie, Academic CME, ACTRIMS, Alkermes, Bayer HealthCare, Biogen, Bionest, Celgene, Clene Nanomedicine, CMSC, ECTRIMS, Forward Pharma A/S, MedDay Pharmaceuticals, Novartis Pharmaceuticals, PRIME, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, Teva Pharmaceuticals and WebMD; royalties are received for outlicensed monoclonal antibodies through UTHealth from Millipore Corporation.
Abstract: P686
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: A higher incidence rate (IR) of malignancies including female breast cancer was observed in ocrelizumab (OCR)-treated patients compared with pooled interferon beta-1a (IFN β-1a) or placebo (PBO)-treated patients.
Objective: To provide an update on the IR of malignancies in the OCR clinical trial programme, in the context of data from other multiple sclerosis (MS) trials (PBO only), epidemiological data sources (MS registries) and the general population (National Cancer Institute [NCI] Surveillance, Epidemiology, and End Results [SEER]).
Methods: Crude IR of first malignancies were calculated across the OCR MS development programme (Phase II: NCT00676715; OPERA I: NCT01247324; OPERA II: NCT01412333; ORATORIO: NCT01194570) in a primary analysis (clinical cut-off dates 22 January-24 July 2015) and updated as of 20 January 2016 and 17 February 2017. Results are contextualised using a meta-analysis of published data of PBO-treated patients from up to 10 MS clinical studies (PBO-MSCS), and data derived from other published MS-specific epidemiological sources (Danish, Swedish or Canadian British Columbia MS registries [DMSR, SMSR, CBCMSR]). Age- and sex-standardised IR of malignancies from the OCR MS programme and the SEER database are provided.
Results: IRs per 100 patient-years (95% confidence interval) for all malignancies and breast cancer in the primary analysis for OCR were 0.43 (0.26-0.66) and 0.26 (0.11-0.54); for the January 2016 update, IRs were 0.44 (0.29-0.65) and 0.23 (0.10-0.46). As of 17 February 2017, the IR of all malignancies was 0.45 (0.32-0.63) for OCR, 0.50 (0.36-0.67) for PBO-MSCS and 0.67 (0.63-0.71) for the DMSR. The rate of female breast cancer was 0.19 (0.09-0.37) for OCR, 0.16 (0.06-0.32) for PBO-MSCS, 0.21 (0.18-0.23) for DMSR, 0.20 (0.18-0.22) for SMSR and 0.14 (0.11-0.16) for CBCMSR. The standardised IR for malignancies excluding non-melanoma skin cancer was 0.24 (0.15-0.41) for OCR and 0.27 (0.27-0.27) for SEER, and for female breast cancer was 0.19 (0.08-0.42) for OCR and 0.12 (0.12-0.13) for SEER.
Conclusions: With additional exposure, the rate of malignancies in OCR-treated patients fall within the range of PBO data from clinical trials in MS and epidemiological data. It is noted that indirect comparisons have limitations, and ongoing data collection through post-approval safety studies are required to characterize the potential risk of malignancies, including breast cancer.
Disclosure: Data provided by LASER; sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK.
S.L. Hauser serves on the board of trustees for Neurona and on scientific advisory boards for Annexon, Symbiotix and Bionure; he has also received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd for CD20-related meetings and presentations.
L. Kappos's institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for Prof Kappos's activities as principal investigator and member or chair of planning and steering committees or advisory boards in trials sponsored by Actelion, Addex, Almirall, Bayer HealthCare Pharmaceuticals, CLC Behring, Genentech, Inc., GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Ono Pharma, Pfizer, Receptos,
F. Hoffmann-La Roche Ltd, Sanofi, Santhera, Siemens, Teva, UCB and XenoPort; license fees for Neurostatus products; and research grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto Foundation, the Novartis Research Foundation and the Roche Research Foundation.
X. Montalban has received speaking honoraria and travel expense reimbursement for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Actelion, Almirall, Bayer, Biogen, Genzyme, Merck, Novartis, Octapharma, Receptos, F. Hoffmann-La Roche Ltd, Sanofi, Teva and Trophos.
P. Chin is an employee of Genentech, Inc. and shareholder of F. Hoffmann-La Roche Ltd.
M.C. Green is an employee of Genentech Inc.
H. Koendgen is an employee and shareholder of F. Hoffmann-La Roche Ltd.
C. Li is an employee of F. Hoffmann-La Roche Ltd.
B. Shi is an employee of F. Hoffmann-La Roche Ltd.
D. Wormser is an employee and shareholder of F. Hoffmann-La Roche Ltd.
J.S. Wolinsky has served on advisory boards, data monitoring or steering committees, has consulting agreements, or received speaker honoraria from the following entities: AbbVie, Academic CME, ACTRIMS, Alkermes, Bayer HealthCare, Biogen, Bionest, Celgene, Clene Nanomedicine, CMSC, ECTRIMS, Forward Pharma A/S, MedDay Pharmaceuticals, Novartis Pharmaceuticals, PRIME, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, Teva Pharmaceuticals and WebMD; royalties are received for outlicensed monoclonal antibodies through UTHealth from Millipore Corporation.