Background
Methods
Selection of investigated antineoplastic drugs
-
i) Drugs used for radiotherapy
-
ii) Drugs for which the incidence of ADRs could not be compared between the Japanese population and non-Japanese populations in the PMDA review reports because the clinical data package for new drug applications in Japan only consisted of the results of the Japanese population. The selection of investigated antineoplastic drugs was done by J.S. and S.U. together.
Analysis of PMDA review reports
-
• We classified drugs based on the mechanism of action into cytotoxic agents, tyrosine kinase inhibitors (TKIs), antibodies including antibody-drug conjugates (ADCs), immuno-oncology treatments (IOs), and hormones; then, we investigated whether there were any ADRs characteristic to the Japanese population for each category.
-
• We determined whether there was any relationship between the higher incidence and dosage or pharmacokinetics in the Japanese population.
Analysis of safety information in labeling
-
• We compared the Japanese and U.S. labeling and examined whether the Japanese labeling contains descriptions based on a higher incidence, including descriptions only in the Japanese labeling. The comparison of the labeling between Japan and the U.S. was based on the Japanese labeling at the time the Japanese review report was finalized and the latest version of the U.S. labeling before the PMDA review report was finalized. The “Warning”, “Important Precautions” and “Serious ADRs” contents in the labeling in Japan were checked to see if they were included in corresponding parts of the labeling in the U.S.
-
• We investigated whether there were any drugs for which the labeling had been revised because of serious ADRs within EPPV (six months of launch). For any with revised labeling, we checked safety data related to the ADRs in the labeling of the drugs.
Results
Status of drugs for which the labeling was revised because of serious ADRs in the early post-marketing phase
Cabazitaxel acetate
Abemaciclib
ADRs with a higher incidence in the Japanese population
Fix date of review report | Drug name | Drug category | Indication | Comparison between Japanese and non-Japanese population | Reference | |
---|---|---|---|---|---|---|
ADRsa | PKb | |||||
Feb 2010 | Panitumumab | Ab | Colorectal carcinoma | NO | Low | [16] |
May 2010 | Temsirolimus | TKI | Renal cell carcinoma | High | NM | [17] |
Jan 2011 | Eribulin mesilate | Ct | Breast cancer | High | ND | [18] |
Aug 2011 | Fulvestrant | Hr | Breast cancer | NO | High | [19] |
Mar 2012 | Crizotinib | TKI | NSCLC | High | High | [20] |
May 2012 | Axitinib | TKI | Renal cell carcinoma | NO | ND | [21] |
Aug 2012 | Pazopanib hydrochloride | TKI | Soft tissue cancer | NO | ND | [22] |
Mar 2013 | Regorafenib | TKI | Colorectal cancer | High | Low | [23] |
Apr 2013 | Pertuzumab | Ab | Breast cancer | High | ND | [24] |
Aug 2013 | Trastuzumab emtansin | Ab | Breast cancer | NO | ND | [25] |
Oct 2013 | Afatinib maleate | TKI | NSCLC | High | ND | [26] |
Jan 2014 | Enzalutamide | Hr | Prostate cancer | NO | ND | [27] |
Apr 2014 | Abiraterone acetate | Hr | Prostate cancer | High | ND | [28] |
Apr 2014 | Cabazitaxel acetate | Ct | Prostate cancer | High | ND | [13] |
Jun 2014 | Nivolumab | IO | Melanoma | High | ND | [29] |
Nov 2014 | Vemurafenib | TKI | Melanoma | High | ND | [30] |
Mar 2015 | Ramucirumab | Ab | Gastric cancer | High | ND | [31] |
May 2015 | Ipilimumab | IO | Melanoma | High | ND | [32] |
Jul 2015 | Vandetanib | TKI | Medullary thyroid cancer | High | High | [33] |
Aug 2015 | Trabectedin | Ct | Soft tissue tumor | High | NM | [34] |
Jan 2016 | Dabrafenib mesilate | TKI | Melanoma | High | NM | [35] |
Feb 2016 | Osimertinib mesilate | TKI | NSCLC | High | ND | [36] |
Mar 2016 | Ceritinib | TKI | NSCLC | High | ND | [37] |
Aug 2016 | Pembrolizumab | IO | Melanoma | NO | ND | [38] |
Jan 2017 | Afliberceot Beta | Ab | Colorectal cancer | High | NM | [39] |
Jul 2017 | Palbociclib | TKI | Breast cancer | High | ND | [40] |
Aug 2017 | Avelumab | IO | Merkel cell carcinoma | High | NM | [41] |
Oct 2017 | Atezolizumab | IO | NSCLC | NO | NM | [42] |
Nov 2017 | Olaparib | TKI | Ovarian cancer | High | ND | [43] |
Apr 2018 | Durvalumab | IO | NSCLC | High | Low | [44] |
Jul 2018 | Abemaciclib | TKI | Breast cancer | High | NM | [15] |
Aug 2018 | Lorlatinib | TKI | NSCLC | NO | ND | [45] |
Nov 2018 | Ebcorfenib/ Binimetinib | TKI | Melanoma | High | ND | |
Nov 2018 | Dacomitinib | TKI | NSCLC | NO | ND | [48] |
Jan 2019 | Apalutamide | Hr | Prostate cancer | NO | ND | [49] |
Apr 2019 | Necitumumab | Ab | Squamous NSCLC | High | ND | [50] |
May 2019 | Entrectinib | TKI | Solid tumors | High | ND | [51] |
Nov 2019 | Darolutamide | Hr | Prostate cancer | NO | ND | [52] |
Jan 2020 | Cabozantinib malate | TKI | Renal cell carcinoma | High | High | [53] |
Feb 2020 | Tepotinib hydrochloride hydrate | TKI | NSCLC | High | ND | [54] |
Feb 2020 | Irinotecan hydrochloride hydrate (liposome injection) | Ct | Pancreatic cancer | High | ND | [55] |
Feb 2020 | Trastuzumab deruxtecan | Ab | Breast cancer | High | NM | [56] |
May 2020 | Capmatinib hydrochloride hydrate | TKI | NSCLC | High | ND | [57] |
Aug 2020 | Niraparib tosilate hydrate | TKI | Ovarian cancer | High | ND | [58] |
Myelosuppression- | ILD | Hepatic impairment | Renal impairment | |
---|---|---|---|---|
Antibody (7 drugs) | 4 (57.1%) | 2 (28.6%) | 2 (28.6%) | 0 (00.0%) |
Cytotoxic (4 drugs) | 4 (100.0%) | 0 (00.0%) | 3 (75.0%) | 0 (00.0%) |
Hormone (5 drugs) | 0 (00.0%) | 0 (00.0%) | 1 (20.0%) | 0 (00.0%) |
IO (6 drugs) | 1 (16.7%) | 1 (16.7%) | 2 (33.3%) | 0 (00.0%) |
TKI (22 drugs) | 11 (50.0%) | 3 (13.6%) | 11 (50.0%) | 7 (31.8%) |
Total (44 drugs) | 20 (45.5%) | 6 (13.6%) | 18 (40.9%) | 7(15.9%) |
Dosage regimen | Higher incidence | Similar incidence | Total |
---|---|---|---|
Same and Fix dose | 19 | 10 | 29 |
Same but adjusted by BW/BSA | 8 | 2 | 10 |
Different | 5 | 0 | 5 |
Description of the incidence of ADRs in the Japanese population in labeling
ADRs with higher incidence in the Japanese population | Description in labeling | |
---|---|---|
Temsirolimus | ILD: JP. 11/20(55%), nJP. 52/178 (29.2%) | ND |
Eribulin mesilate | Neutropenia: JP. 80/81 (98.8%), nJP. 481/827 (58.2%) | a) |
Crizotinib | Neutropenia: JP. 3/15 (20%), nJP. 3/104 (2.9%) | a) |
Regorafenib | ALT increased: JP. 13/65 (20%), nJP. 15/433 (3.4%) | ND |
Pertuzumab | ILD: JP. 2/26 (7.7%), nJP. 7/381 (1.8%) | b) |
Afatinib maleate | ILD: JP. 4/54 (7.4%), nJP. 3/175 (1.7%) | a) |
Abiraterone acetate | Hepatotoxicity: JP. 20/48 (41.7%), nJP. 90/543 (16.6%) | a) |
Cabazitaxel acetate | Myelosuppression: JP. 44/44 (100%), nJP. 130/371 (35%) AST increased: JP. 6/47 (12.5%), nJP. 4 (1.1%) | ND |
Nivolumab | AST increased: JP. 14/52 (26.9%), nJP. 28/345 (8.1%) | a) |
Vemurafenib | Hepatic impairment: JP. 5/11 (45.5%), nJP. 91/337 (27.5%) | ND |
Ramucirumab | Neutropenia: JP. 58/68 (85.3%), nJP. 120/259 (27.5%) | b) |
Ipilimumab | AST increased: JP. 4/20 (20%), nJP. 1/131 (0.8%) | ND |
Vandetanib | ILD: JP. 1/14 (7.1%), nJP. 2/231 (0.9%) Renal impairment: JP. 5/14 (35.7%), nJP. 49/231(21.2%) Hepatic impairment: JP. 3/14 (21.4%), nJP. 29/231 (8.2%) | b) (Hepatic impairment) |
Trabectedin | Neutropenia: JP. 64/73 (87.7%), nJP. (75/130 (57.7%) ALT increased: JP. 52/73 (71.2%), NJP. 72/130 (55.4%) | a) |
Dabrafenib mesilate | Hepatic impairment: JP. 6/12 (50%), nJP. 39/398 (9.8) Myelosuppression: JP. 8 (66.7%), nJP. 48/398 (12.1%) | b) for hepatic impairment |
Osimertinib mesilate | White blood cell count decreased: JP. 21/80 (26.3%), nJP. 10/331 (3%) | ND |
Ceritinib | Blood ALP increased: JP. 11/19 (57.9%), nJP. 14/105 (13.3%) Blood creatinine increased: JP. 9/19 (47.4%), nJP. 17/105 (16.2%) White blood cell count decreased: JP. 4/19 (21.1%), nJP. 2/105 (1.9%) | ND |
Afliberceot Beta | Neutropenia: JP. 46/62 (74.2%), nJP. 238/611 (39.0%) | a) |
Palbociclib | White blood cell count decreased: JP. 17/27 (63.0%), nJP. 88/318 (27.7%) ALT increased: JP. 7/32 (21.9%), nJP. 37/412 (9.0%) | ND |
Avelumab | Anemia: JP. 8/43 (18.6%), nJP. 105/1764 (6.0%) | ND |
Olaparib | White blood cell count decreased: JP. 5/8 (62.5%), nJP. 6/187 (3.2%) | b) |
Durvalumab | ILD: JP. 53/72 (73.6%), nJP. 108/403 (26.8%) | ND |
Abemaciclib | Neutrophil count decreased: JP. 34/43 (79.1%), nJP. 103/277 (37.2%) ALT increased: JP. 15/43 (34.9%), nJP 24/277 (8.7%) Blood creatinine increased: JP. 13/43 (30.2%), nJP. 24/277 (8.7%) | ND |
Ebcorfenib/ Binimetinib | Anemia: JP. 3/10 (30%), nJP. 50/439 (11.4%) | ND |
Necitumumab | Neutrophil count decreased: JP. 53/90 (58.9%), nJP. 8/538 (1.5%) ALT increased: JP. 17/90 (18.9%), NJP 27/538 (5.0%) | ND |
Entrectinib | Blood creatinine increased: JP. 11/16 (68.8%), nJP. 48/190 (25.3%) AST increased: JP. 9/16 (56.3%), nJP. 32/190 (16.8%) White blood cell count decreased: JP. 4/16 (25.0%), nJP. 9/190 (4.7%) | ND |
Cabozantinib malate | Renal impairment: JP. 15/35 (42.9%), nJP. 70/331 (21.1%) Hepatic impairment: JP. 25/35 (71.4%), nJP. 93/331 (28.1%) | b) for hepatic impairment |
Tepotinib hydrochloride hydrate | Blood creatinine increased: JP. 9/17 (52.9%), nJP. 22/113 (19.5%) | b) |
Irinotecan hydrochloride hydrate (liposome injection) | Hepatic impairment: JP. 19/46 (41.3%), nJP. 20/117 (17.1%) Myelosuppression: JP. 38/46 (82.6%), nJP. 76/117 (65.0%) | b) for hepatic impairment |
Trastuzumab deruxtecan | Neutrophil count decreased: JP. 22/30 (73.3%), nJP. 35/154 (22.7%) ILD: JP. 51/316 (16.1%), nJP. 21/329 (6.4%) AST increased: JP. 7/21 (33.3%), nJP. 2/29 (6.9%) | ND |
Capmatinib hydrochcrolide hydrate | Blood creatinine increased: JP. 25/45 (55.6%), nJP. 60/289 (20.8%) ALT increased: JP. 10/45 (22.2%), nJP. 32/289 (11.1%) Platelet count decreased: 8/45 (17.8%), nJP. 6/289 (2.1%) | b) for renal impairment |
Niraparib tosilate hydrate | Platelet count decreased: JP. 12/19 (63.2%), nJP. 77/367 (21.0%) | ND |