Table 4 Summary of clinical trials investigating the combination of ADCs and radiotherapy
From: The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors
NCT number | Start | Type of study | No | RT site | RT type | RT prescription | Drug | Timing | Treatment setting | Toxicity (Radiation-related) | Efficacy |
|---|---|---|---|---|---|---|---|---|---|---|---|
NCT01196052 [34] | 2010 | Phase II (subgroup) | 116 | Beast/chest wall/regional node | CFRT | RT prescription according to local standards | T-DM1 ± Trastuzumab | Con/Seq (pre/post-RT) | HER2 + early-stage BC received (neo)adjuvant | NR | NA |
NCT01772472 [35] | 2013 | Phase III (subgroup) | 624 | Beast/chest wall/regional node | CFRT | RT prescription according to local standards | T-DM1 | Con | HER2 + early BC patients undergoing breast-conserving surgery or that with T3N + or T4 and/or with N2-3 | RT-related skin injury, 13.2% grade 1; 10.8% grade 2; 1.4% grade 3 or more. Radiation pneumonitis, 0.41% grade 1; 0.82%grade 2; 0.27% grade3. Pulmonary radiation injury, 0.14% grade 1 | Positive |
Julie A. Carlson [36] | 2014 | Case series | 7 | Tumor | SRS | 16–24 Gy/1F | T-DM1 | Seq (3 d-49 d post-RT) | HER2 + BC patients with brain metastases | Radiation necrosis 57% | NA |
NCT02573324 [37] | 2015 | Phase III | 639 | Tumor/TB | CFRT | 60 Gy/30 F or 59.4 Gy/33 F | TMZ + Depatux-m | Con | EGFR-amplification newly diagnosed GBM | Seizure, 20.4% any grade; 5% grade 3; 0.6% grade 4. No specific radiation-related toxicity was reported | Negative |
NCT02590263 [38] | 2015 | Phase I/II | 15 | Tumor/TB | CFRT | 60 Gy/30 F in 42 days | TMZ + Depatux-m | Con | EGFR-amplification newly diagnosed WHO grade III/IV glioma | RT-related skin injury, 73% ≥ grade3. Headache, 20% ≥ grade3 |  |
NA | |||||||||||
A Géraud [39] | 2016 | Case series | 3 | Dorsal vertebras; sacrum; left shoulder | SRS | 15 Gy/5 F or 8 Gy/1 F | T-DM1 | Con | HER2 + metastatic BC | No side effects | Positive |
William Jacot [40] | 2016 | Retrospective study | 36 | Tumor/whole brain | SRS/WBRT | NR | T-DM1 | Seq (pre-RT) | HER2 + BC patients with brain metastases | NR | Positive |
Arthur Geraud [41] | 2017 | Retrospective study | 12 | Tumor ± whole brain | SRS ± WBRT | NR | T-DM1 | Con/Seq (pre-RT) | HER2 + BC patients with brain metastases | Radiation necrosis, 50% in Con group and 28.6% in Seq group. Other toxicity, alopecia; memory disorders; locomotor disorders; balance disorders; and visual disorders | NA |
Zita Zolcsák [42] | 2020 | Retrospective study | 14 | TB/Breast/ chest wall | CFRT | 50 Gy/25 F ± boost of 14.5 Gy-16 Gy to TB | T-DM1 | Con | Nonmetastatic HER + BC patients with residual invasive disease following neoadjuvant therapy | Radiodermatitis, 86% grade 1; 14% grade 2; RT-related fatigue, 14% grade 1; Pain in the irradiation zone, 7% grade 1; LVEF decrease, 14% grade 2 | NA |
Matthew N. Mills [43] | 2021 | Retrospective study | 16 | Tumor | SRS | 21 Gy (14 Gy-24 Gy)/1 F or 25 Gy (20 Gy-30 Gy)/13-5 F | T-DM1 | Con/Seq (pre/post-RT) | HER2 + BC patients with brain metastases | Radiation necrosis, 3%. Other toxicity, headaches and fatigue | Positive |
NCT05979740 (recruiting) | 2023 | Phase II | 6 | Bladder | CFRT |  ≥ 50 Gy in about 30 F | RC48 + PD-1 | Con | MIBRC with high HER2 expression (IHC 2 + or 3 +) and could be treated with bladder conserving therapy with maximum TURBT | NR | NA |