Table S1.
EMA/PDCO PIP decisions oncology
| Substance | Indication | PIP number | Decision year | Until | Classification |
|---|---|---|---|---|---|
| Aut T-Cells ag CD19 | CT-resistant CD19+ leukemia or lymphoma | EMEA-001654-PIP01-14 | 2015 | DEC 2021 | Leukemia |
| TH-302 | Ewing and soft tissue sarcoma | EMEA-001483-PIP01-13 | 2015 | DEC 2026 | Solid tumor |
| MK-8669,/AP23573 | Solid malignant tumors | EMEA-000458-PIP01-08 | 2010 | JUN 2019 | Solid tumor |
| HSV-TK gene | Operable supratentorial HGG | EMEA-000140-PIP01-07 | 2008 | 4y after ini | Solid tumor |
| MAB (MPDL3280A) | PD-L1 pos malignant neoplasms | EMEA-001638-PIP01-14 | 2015 | JUN 2015 | Solid tumor |
| MAB (MK-3475) | Melanoma or PD-L1+ tumor/lymphoma | EMEA-001474-PIP01-13 | 2014 | OCT 2023 | Solid tumor |
| Aprepitant | Nausea and vomiting in chemo/after OP | EMEA-000144-PIP01-07-M05 | 2014 | OCT 2014 | Adjuvant to CT/SCT |
| Navitoclax (ABT | ALL, NHL | EMEA-000478-PIP01-08-M01 | 2011 | DEC 2019 | Leukemia |
| Bevacizumab | HGG | EMEA-000056-PIP03-10-M02 | 2014 | SEP 2016 | Solid tumor |
| Bevacizumab | RMS and non-RMS soft tissue sarcoma | EMEA-000056-PIP01-07-M02 | 2014 | SEP 2016 | Solid tumor |
| Blinatumomab | ALL | EMEA-000574-PIP02-12 | 2014 | JUL 2023 | Leukemia |
| Bosutinib | CML | EMEA-000727-PIP01-09 | 2010 | DEC 2016 | Leukemia |
| Brentuximab | Anaplastic LCL and HL | EMEA-000980-PIP01-10-M02 | 2014 | DEC 2018 | Lymphoma |
| Cabozantinib | Solid tumors w/MET, VEGFR, and/or RET PA | EMEA-001143-PIP01-11 | 2012 | DEC 2016 | Solid tumor |
| Casopitant | CT related and post OP nausea and vomiting | EMEA-000154-PIP01-07 | 2009 | MAY 2013 | Adjuvant to CT/SCT |
| Cediranib maleate | HGG | EMEA-000477-PIP01-08 | 2010 | DEC 2015 | Solid tumor |
| MAB (NSC764038) | Neuroblastoma | EMEA-001285-PIP01-12-M01 | 2013 | JAN 2014 | Solid tumor |
| MAB (APN311) | Neuroblastoma | EMEA-001314-PIP01-12 | 2014 | DEC 2016 | Solid tumor |
| Cilengitide | HGG | EMEA-000550-PIP02-10-M01 | 2013 | NOV 2018 | Solid tumor |
| Cobimetinib | Malignancies w/Ras, Raf or MEK pathway activation | EMEA-001425-PIP01-13-M01 | 2014 | JUN 2026 | Solid tumor |
| Cyclophosphamide | Malignant diseases | EMEA-000530-PIP02-11 | 2012 | MAR 2015 | Malignant diseases |
| Dabrafenib | BRAF V600-mutant melanomas and solid tumors | EMEA-001147-PIP01-110M02 | 2014 | JUL 2019 | Solid tumor |
| Dasatinib | Ph+ (BCR-ABL translocation)-positive ALL and AML | EMEA-000567-PIP01-09-M04 | 2013 | JUN 2018 | Leukemia |
| Decitabine | AML | EMEA-000555-PIP01-09-M04 | 2013 | JUL 2021 | Leukemia |
| Denosumab | Giant cell tumor of bone and more, see below | EMEA-000145-PIP01-07-M07 | 2015 | NOV 2017 | Solid tumor |
| Dextran | Visualization of lymphatic drainage of solid malignant tumors for diagnostic purposes | EMEA-001255-PIP01-11 | 2012 | OCT 2015 | Diagnostic |
| Docetaxel | Nasopharyngeal carcinoma | EMEA-000029-PIP01-07 | 2008 | SEP 2009 | Solid tumor |
| Elacytarabine | AML | EMEA-001121-PIP01-10 | 2012 | SEP 2019 | Leukemia |
| Eltrombopag | TP due to treated M/L leukemia or solid tumors | EMEA-000170-PIP02-10-M02 | 2015 | DEC 2019 | Adjuvant to CT/SCT |
| Enzastaurin | High-risk B-cell NHL | EMEA-001033-PIP02-11 | 2013 | JUN 2022 | Lymphoma |
| Eribulin | RMS and non-RMS soft tissue sarcoma | EMEA-001261-PIP01-11-M01 | 2015 | NOV 2029 | Solid tumor |
| Febuxostat | Hyperuricemia tumor lysis syndrome | EMEA-001417-PIP01-12 | 2014 | DEC 2017 | Adjuvant to CT/SCT |
| Fosaprepitant | Nausea and vomiting in chemotherapy in R after FLT | EMEA-000406-PIP01-08-M04 | 2014 | OCT 2014 | Adjuvant to CT/SCT |
| Glucarpidase | Methotrexate toxicity | EMEA-001391-PIP01-12 | 2013 | JUN 2012 | Adjuvant to CT/SCT |
| HSV TK | Adjunctive treatment in HCT | EMEA-001370-PIP02-13 | 2014 | DEC 2022 | Adjuvant to CT/SCT |
| Idelalisib | Lymphomas | EMEA-001350-PIP02-13-M01 | 2014 | JUL 2021 | Lymphoma |
| Imatinib mesilate | Ph+ (BCR-ABL translocation)-positive ALL et al | EMEA-000463-PIP01-08-M03 | 2012 | JUN 2011 | Leukemia |
| Ipilimumab | Malignomas except melanoma, NS, H&L tissue | EMEA-000117-PIP01-07-M07 | 2015 | JUN 2018 | Solid tumor |
| Ipilimumab | Melanoma | EMEA-000117-PIP02-10-M03 | 2014 | JUN 2018 | Solid tumor |
| l-AGN in erys | ALL | EMEA-000341-PIP02-09-M01 | 2014 | DEC 2020 | Leukemia |
| Lenvatinib | Follicular or papillary thyroid cancer; osteosarcoma | EMEA-001119-PIP02-12-M02 | 2014 | DEC 2022 | Solid tumor |
| Mercaptopurine | ALL | EMEA-000350-PIP01-08 | 2009 | DEC 2009 | Leukemia |
| Midostaurin | AML, malignant mastocytosis, mast cell leukemia | EMEA-000780-PIP01-09-M01 | 2014 | DEC 2019 | Leukemia |
| ABT-869 | Solid malignant tumors (refractory to standard therapy) | EMEA-000389-PIP01-08-M01 | 2011 | JUN 2017 | Solid tumor |
| Nilotinib | Gastrointestinal stromal tumor, CML | EMEA-000290-PIP01-08-M03 | 2013 | SEP 2015 | Leukemia |
| Nivolumab | Malignomas except NS, haematopoiet and lymphoid tissue | EMEA-001407-PIP01-12 | 2014 | AUG 2024 | Solid tumor |
| Obinutuzumab | ALL, mature B-cell lymphoma | EMEA-001207-PIP01-11 | 2013 | JUN 2024 | Lymphoma |
| Ombrabulin | RMS and non-RMS soft tissue sarcoma | EMEA-000800-PIP01-09-M01 | 2011 | DEC 2018 | Solid tumor |
| Paclitaxel | Solid malignomas, CT-naïve metastasized melanoma | EMEA-001308-PIP01-12 | 2013 | DEC 2022 | Solid tumor |
| Pazopanib | RMS, non-RMS, soft tissue S, EwingS | EMEA-000601-PIP01-09-M02 | 2014 | SEP 2021 | Solid tumor |
| Pixantrone | NHL | EMEA-000713-PIP02-10-M03 | 2015 | NOV 2023 | Lymphoma |
| Plerixafor | Myelosuppression caused by chemotherapy | EMEA-000174-PIP01-07-M03 | 2013 | JUN 2017 | Adjuvant to CT/SCT |
| XM22 | Chemotherapy-induced febrile neutropenia | EMEA-001019-PIP01-10-M02 | 2014 | APR 2018 | Adjuvant to CT/SCT |
| Ponatinib | CML resistant or intolerant to prior TKI therapy | EMEA-001186-PIP01-11 | 2012 | DEC 2020 | Leukemia |
| Pralatrexate | NHL, HL, T-cell lymphoma | EMEA-000619-PIP02-10 | 2010 | MAR 2021 | Lymphoma |
| RO5185426 | BRAF V600 + unresectable melanoma | EMEA-000978-PIP01-10 | 2011 | MAR 2017 | Solid tumor |
| CSF/fusion protein | Prevention of chemotherapy-induced neutropenia | EMEA-001042-PIP02-11 | 2011 | DEC 2014 | Adjuvant to CT/SCT |
| MAB (RO4858696) | Ewing sarcoma | EMEA-000281-PIP01-08-M02 | 2009 | DEC 2016 | Solid tumor |
| Recombinant L-AGN | ALL and lymphoblastic lymphoma | EMEA-000013-PIP01-07-M03 | 2013 | NOV 2012 | Leukemia |
| Regorafenib | Solid malignant tumor(s) | EMEA-001178-PIP01-11-M01 | 2014 | DEC 2020 | Solid tumor |
| Rituximab | Autoimmune arthritis, diffuse large B-cell L | EMEA-000308-PIP01-08-M02 | 2012 | JUN 2019 | Leukemia |
| Sonidegib | Medulloblastoma | EMEA-000880-PIP02-11-M02 | 2013 | DEC 2024 | Solid tumor |
| Sunitinib | Gastrointestinal stromal tumor | EMEA-000342-PIP01-08-M04 | 2015 | JUN 2014 | Solid tumor |
| Talimogene | Solid malignant non-CNS tumors | EMEA-001251-PIP01-11 | 2013 | DEC 2024 | Solid tumor |
| Tivantinib | Hepatoblastoma | EMEA-001284-PIP01-12 | 2012 | Refused W | Solid tumor |
| Trametinib | Melanoma | EMEA-001177-PIP01-11-M01 | 2014 | OCT 2019 | Solid tumor |
| Treosulfan | Preparation of AHSCT | EMEA-000883-PIP01-10-M02 | 2014 | DEC 2016 | Adjuvant to CT/SCT |
| Vandetanib | Medullary thyroid carcinoma | EMEA-000052-PIP01-07-M03 | 2013 | OCT 2011 | Solid tumor |
| Veliparib | HGG | EMEA-000499-PIP02-10 | 2011 | DEC 2020 | Solid tumor |
| Volasertib | AML | EMEA-000674-PIP02-11 | 2013 | DEC 2023 | Leukemia |
| Vosaroxin | AML | EMEA-001450-PIP01-13 | 2014 | JUL 2023 | Leukemia |
Notes: Denosumab indications: 1) Bone loss associated with sex hormone ablative therapy; 2) Prevention of skeletal related events in patients with bone metastases; 3) Treatment of chronic idiopathic arthritis (including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis); and 4) Treatment of giant cell tumor of bone.
Abbreviations: l-AGN, l-Asparaginase; CT, chemotherapy; HGG, high grade glioma; LCL, large cell lymphoma; HL, Hodgkin lymphoma; NHL, Non-Hodgkin lymphoma; ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia; PA, pathway activation; Ph+, Philadelphia chromosome-positive; AHSCT, allogeneic hematopoietic stem cell transplant; TKI, tyrosine kinase inhibitor; TP, thrombocytopenia; R, remission; FLT, front line therapy; HCT, hematopoietic cell transplantation; H&L, hematopoietic and lymphoid tissue; S, sarcoma; L, lymphoma; CD19+, CD19 positive; PIP, pediatric investigation plan; JAN, January; MAR, March; APR, April; Jun, June; JUL, July, SEP, September; OCT, October; NOV, November; DEC, December; 4y after ini, 4 years after initiation; Refused W, refused waiver; MAB, monoclonal antibody; w/, with.