Table 1.
Characteristics of included studies reporting on concurrent antiangiogenic-antiresorptive therapy, MRONJ, and summary of outcome parameters
|
Study ID (Last name, year of publication)
|
Study design
|
Total study sample
|
Study duration
|
AA drug
|
Dose, route, frequency (AA drug)
|
MRONJ cases/
total sample
(AA only) |
Exposure time to MRONJ, median (range)
|
AR drug
|
Dose, route frequency (AR only)
|
MRONJ cases/ total sample (AR onlu)
|
Exposure time to MRONJ, median (range)
|
MRONJ cases/ total sample (AA+AR)
|
Exposure time to MRONJ, median (range)
|
Additional chemotherapy
|
| Aragon-Ching (2009)51 | Retrospective (Phase II trial) | 60 | Apr 2005– Sep 2007 | BEV | 15 mg/kg IVI Q3W | – | NA | BP (ZOL) | 3.5–4 mg/ Q3–Q4W IVI | – | NA | 11/55 | AR- 19 (3–36)* AA- 10 (3–17)* | THAL, TXT, PDN |
| Beuselinck (2012)2 | Retrospective cohort | 76 | Nov 2005– May 2012 | SUN, SOR | NR | – | NA | BP (ZOL, PAM, IBAN) | NR Q4W | – | NA | 5/52 | AR- 18 (4–60) AA- 6 (2–39) | NR |
| Broom (2015)3 | Prospective RCT | 30 | Feb 2010– Oct 2011 | EVE | 10 mg daily | 0/15 | NA | BP (ZOL) | 4 mg/Q4W IVI | – | NA | 0/15 | NA | NR |
| Christodoulou (2009)46 | Retrospective cohort | 116 | Jun 2007– Jun 2008 | BEV, SUN, SOR | NR | – | NA | BP (ZOL, IBAN) | ZOL: 4 mg/ Q4W 15-– min IVI | 1/91 | 18 | 4/25 | AR- 2 9(15–78) AA-11.5 (1–20)* | NR |
| Francini (2011)54 | Prospective cohort | 59 | Jul 2007– Dec 2009 | BEV | 15 mg/kg IVI Q3W | – | NA | BP (ZOL) | 4 mg/Q4W 15-min IVI | – | NA | 0/59 | NA | MBC: TXT/T/EC NSCLC: GC/EP |
| Guarneri (2010a)52† | Retrospective RCTs (AVADO, RIBBON–1) | 1309 | NR | BEV | 7.5 or 15 mg/kg IVI Q3W | 2/1075 | 4.5 (2–7) | BP | NR | 0/99 | NA | 2/233 | AR- 3.2 (0.5–6) AAD- 3.5 (3–6) | AVADO:TXT RIBBON-1: CAPE/ TXT/T/EC/AC ± 5–FU |
| Guarneri (2010b)52† | Retrospective non– RCT (ATHENA) | 2251 | NR | BEV | NR | 0/1826 | NA | BP (ZOL, PAM, CLOD, IBAN) | NR | – | NA | 10/425 | AR- NR AA- 9 (5–15) | TXT/PTX ±5-FU/ VNB |
| Guillot (2018)47 | Retrospective cohort | 41 | Jan 2013– Nov 2016 | SUN, PAZ, EVE, TEM, AXT | NR | – | NA | Dmab | NR | – | NA | 7/41 | AR- 19.9 (NR) AA- NR | NR |
| McKay (2014)53 | Retrospective Phase II (n = 5), Phase III (n = 3) | 2749 | Jan 2003– Nov 2011 | SUN, SOR AXT, TEM | NR | 1/2464 | NR | BP | NR | – | NA | 6/285 | NR | NR |
| Pilanci (2015)48 | Retrospective cohort | 97 | Mar 2006– Dec 2013 | Tmab | NR | – | NA | BP (ZOL) | NR | 5/66 | 38 (13–55)* | 8/31 | AR- 42(26–78)* AA- NR | AI, CT |
| Smidt-Hansen (2013)49 | Retrospective cohort | 46 | Aug 2010– Dec 2011 | SUN, SOR, BEV, PAZ, EVE, TEM | SUN: 50 mg/d 4W on/2W off; SOR: 400 mg BD; BEV: 10 mg/kg Q2W; PAZ: 800 mg/d; EVE: 10 mg/d; TEM: 25 mg/wk IV | – | NA | BP (ZOL) | 4 mg/Q6W IVI | – | NA | 7/46 | AR- NR (3.7–26.2) AA-NR (3.7–17.7) | NR |
| van Cann (2018)50 | Retrospective cohort | 623 | Jan 2005– Jan 2017 | SUN, PAZ, AXT, SOR VAN, EG, TIVO | NR | – | NA | BP, Dmab | NR | 58/533 | 19 (1–144) | 10/90 | AR- 5 (1–55) AA- 4 (1–48) | NR |
Published as a combination study; raw data retrieved for analysis.
Computed from raw data.
MRONJ: medication-related osteonecrosis of the jaw; AA: antiangiogenic; AR: antiresorptive; ZOL: zoledronate; IBAN: ibandronate; PAM: pamidronate; CLOD: clodronate; BEV: bevacizumab; EVE: everolimus; SUN: sunitinib; SOR: sorafenib; PAZ: pazopanib; TEM: temsirolimus; Tmab: trastuzumab; AXT: axitinib; VAN: vandetanib; REG: regorafenib; TIVO: tivozanib; TXT: docetaxel; PTX: paclitaxel; THAL: thalidomide; PDN: prednisolone; VNB: vinorelbine; PBO: placebo; SC: subcutaneous; IVI: intravenous infusion; NR: not reported/not retrievable; MBC: metastatic breast cancer; NSCLC: non-small lung cell cancer; EC: epirubicin and cyclophosphamine; GC: gemcitabine and cisplatin: EP: etoposide and cisplatin; CAPE: capecitabine; AC: doxorubicin and cyclophosphamide; 5-FU: 5-fluorouracil; AI: aromatase inhibitor; CT: chemotherapy; W: week.