Results of randomized phase 3 trials in early-stage unfavorable HL
| . | N/arm . | Clinical characteristic, % . | Treatment . | PFS, % (95% CI) . | OS, % (95% CI) . | Reason for death, % . | SN, %(95% CI) . | SN SIR (95% CI) . | Reference . |
|---|---|---|---|---|---|---|---|---|---|
| Non–PET-guided therapy | |||||||||
| HD.6 | 196 | CS I, 33 CS II, 67 BSs, 0 Bulk/LMM, 0 EN, NR | 4×-6×ABVD | 12-y FFDP, 87 | 12 y, 94 | HL (3), SN (2), CVasc (1) | 5.1 (NR) | NR | 32 |
| 64 | 35-Gy STNI | 87 | 98 | SN (<1) | 11.3 (NR) | NR | |||
| 139 | 2×ABVD + 35-Gy STNI | 94 | 81 | SN (6.4), HL (3), CVasc (1), other (5.7) | NR | ||||
| HD8 | 532 | CS I, 8 CS II, 90 CS III, 2 BSs, 26 Bulk/LMM, 18 EN, 7 >60 y, 8 | 2×COPP/ABVD + 30-Gy EFRT | 15 y, 72.7 (8.2-77.2) | 15 y, 80.5 (76.7-84.3) | SN (6), HL (3), CVasc (2) | 17 (13-21) | 3.6 (2.9-4.5) | 5 |
| 532 | 2×COPP/ABVD + 30-Gy IFRT | 73.8 (69.2-78.3) | 82.4 (78.7-86.0) | SN (5), HL (3), CVasc (3) | 14 (10-18) | 2.6 (2.0-3.3) | |||
| HD11 | 356 | CS I, 6 CS II, 94 BSs, 29 Bulk/LMM, 20 EN, 10 >60 y, 7 | 4×ABVD + 30-Gy IFRT | 10 y, 83.3 (78.9-87.6) | 10 y, 90.8 (87.5-94.2) | HL (3), SN (1) | 6 (3-9) | 1.4 (0.8-2.3) | 5 |
| 347 | 4×BVD + 20-Gy IFRT | 74.6 (69.3-79.9) | 89.5 (86.1-93.0) | HL (3), SN (2) | 7 (4-9) | 2.4 (1.5-3.7) | |||
| 341 | 4×BEACOPPb + 30-Gy IFRT | 82.9 (78.4-87.3) | 90.5 (87.2-93.9) | HL (3), SN (2) | 7 (4-10) | 2.2 (1.4-3.3) | |||
| 351 | 4×BEACOPPb + 30-Gy IFRT | 81.9 (77.3-86.5) | 91.4 (88.2-94.7) | HL (3), SN (2) | 5 (3-8) | 1.7 (1-2.6) | |||
| HD14 | 765 | CS I, 4.8 CS II, 95.2 BSs, 29.9 Bulk/LMM, 18.7 EN, 8.1 >50 y, 9.3 >60 y, 0 | 4×ABVD + 30-Gy IFRT | 5 y, 89.1 (86.3-91.9) | 5 y, 96.8 (95.2-98.4) | HL, SN, toxicity second line (<1 each) | 2.2 (NR) | NR | 2 |
| 763 | 2×BEACOPPesc + 2×ABVD + 30 Gy IFRT | 95.4 (93.7-97.1) | 97.2 (95.8-98.6) | HL, SN (<1 each) | 2.0 (NR) | NR | |||
| E2496 | 135 | CS I, 11 CS II, 89 BSs, 52 Bulk/LMM, 100 EN, 12.5 >60 y, NR | 6×-8×ABVD + 36-Gy IFRT | 5-y FFS, 85 (NR) | 5 y, 96 (NR) | Respiratory, HL (<1 each) | NR | NR | 37 |
| 129 | 6×-8×Stanford V + 36-Gy IFRT | 79 (NR) | 92 (NR) | Toxicity of second line (3), HL (1.5) | NR | NR | |||
| PET-guided therapy | |||||||||
| H10U | PET-2−, 292 | CS I, 14 CS II, 86 BSs, 40.3 Bulk/LMM, 42.2 EN, NR >60 y, NR | 4×ABVD + 30(+6)-Gy INRT | 5 y, 92.1 (88.0-94.8) | 5 y, 96.7 (93.7-98.3) | HL, SN, CVasc (<1 each) | 3.4 (NR) | NR | 6,26 |
| PET-2−, 302 | 6×ABVD | 89.6 (85.5-92.6) | 98.3 (96.0-99.3) | HL, SN (<1 each) | 2.9 (NR) | NR | |||
| 320* | 4×ABVD + 30(+6)-Gy INRT | 3 y, 95.5 (92.5-97.3) | 3 y, 99.7 (97.7-100) | HL, unknown (<1 each) | 1.2 (NR) | NR | |||
| PET-2+, 192† | 4×ABVD + 30(+6)-Gy INRT | 77.4 (70-4-82.9) | 89.3 (83.4-93.2) | HL, SN (<1 each) | 2.1 (NR) | NR | |||
| PET-2+, 169† | 2×ABVD + 2×BEACOPPesc + 30(+6)-Gy INRT | 90.6 (84.7-94.3) | 96.0 (91.1-98.2) | HL (6), SN (<1), toxicity of second line (<1) | 2.4 (NR) | NR | |||
| PET-3−, 211 | 3×ABVD + 30-Gy IFRT | 90.8 (86.9-94.8) | 99.0 (97.6-100) | HL (0.9) | NR | NR | |||
| PET-3+, 145 | 4×ABVD + 30-Gy IFRT | 87.6 (NR) | 95.5 (NR) | HL (3.4) | NR | NR | |||
| . | N/arm . | Clinical characteristic, % . | Treatment . | PFS, % (95% CI) . | OS, % (95% CI) . | Reason for death, % . | SN, %(95% CI) . | SN SIR (95% CI) . | Reference . |
|---|---|---|---|---|---|---|---|---|---|
| Non–PET-guided therapy | |||||||||
| HD.6 | 196 | CS I, 33 CS II, 67 BSs, 0 Bulk/LMM, 0 EN, NR | 4×-6×ABVD | 12-y FFDP, 87 | 12 y, 94 | HL (3), SN (2), CVasc (1) | 5.1 (NR) | NR | 32 |
| 64 | 35-Gy STNI | 87 | 98 | SN (<1) | 11.3 (NR) | NR | |||
| 139 | 2×ABVD + 35-Gy STNI | 94 | 81 | SN (6.4), HL (3), CVasc (1), other (5.7) | NR | ||||
| HD8 | 532 | CS I, 8 CS II, 90 CS III, 2 BSs, 26 Bulk/LMM, 18 EN, 7 >60 y, 8 | 2×COPP/ABVD + 30-Gy EFRT | 15 y, 72.7 (8.2-77.2) | 15 y, 80.5 (76.7-84.3) | SN (6), HL (3), CVasc (2) | 17 (13-21) | 3.6 (2.9-4.5) | 5 |
| 532 | 2×COPP/ABVD + 30-Gy IFRT | 73.8 (69.2-78.3) | 82.4 (78.7-86.0) | SN (5), HL (3), CVasc (3) | 14 (10-18) | 2.6 (2.0-3.3) | |||
| HD11 | 356 | CS I, 6 CS II, 94 BSs, 29 Bulk/LMM, 20 EN, 10 >60 y, 7 | 4×ABVD + 30-Gy IFRT | 10 y, 83.3 (78.9-87.6) | 10 y, 90.8 (87.5-94.2) | HL (3), SN (1) | 6 (3-9) | 1.4 (0.8-2.3) | 5 |
| 347 | 4×BVD + 20-Gy IFRT | 74.6 (69.3-79.9) | 89.5 (86.1-93.0) | HL (3), SN (2) | 7 (4-9) | 2.4 (1.5-3.7) | |||
| 341 | 4×BEACOPPb + 30-Gy IFRT | 82.9 (78.4-87.3) | 90.5 (87.2-93.9) | HL (3), SN (2) | 7 (4-10) | 2.2 (1.4-3.3) | |||
| 351 | 4×BEACOPPb + 30-Gy IFRT | 81.9 (77.3-86.5) | 91.4 (88.2-94.7) | HL (3), SN (2) | 5 (3-8) | 1.7 (1-2.6) | |||
| HD14 | 765 | CS I, 4.8 CS II, 95.2 BSs, 29.9 Bulk/LMM, 18.7 EN, 8.1 >50 y, 9.3 >60 y, 0 | 4×ABVD + 30-Gy IFRT | 5 y, 89.1 (86.3-91.9) | 5 y, 96.8 (95.2-98.4) | HL, SN, toxicity second line (<1 each) | 2.2 (NR) | NR | 2 |
| 763 | 2×BEACOPPesc + 2×ABVD + 30 Gy IFRT | 95.4 (93.7-97.1) | 97.2 (95.8-98.6) | HL, SN (<1 each) | 2.0 (NR) | NR | |||
| E2496 | 135 | CS I, 11 CS II, 89 BSs, 52 Bulk/LMM, 100 EN, 12.5 >60 y, NR | 6×-8×ABVD + 36-Gy IFRT | 5-y FFS, 85 (NR) | 5 y, 96 (NR) | Respiratory, HL (<1 each) | NR | NR | 37 |
| 129 | 6×-8×Stanford V + 36-Gy IFRT | 79 (NR) | 92 (NR) | Toxicity of second line (3), HL (1.5) | NR | NR | |||
| PET-guided therapy | |||||||||
| H10U | PET-2−, 292 | CS I, 14 CS II, 86 BSs, 40.3 Bulk/LMM, 42.2 EN, NR >60 y, NR | 4×ABVD + 30(+6)-Gy INRT | 5 y, 92.1 (88.0-94.8) | 5 y, 96.7 (93.7-98.3) | HL, SN, CVasc (<1 each) | 3.4 (NR) | NR | 6,26 |
| PET-2−, 302 | 6×ABVD | 89.6 (85.5-92.6) | 98.3 (96.0-99.3) | HL, SN (<1 each) | 2.9 (NR) | NR | |||
| 320* | 4×ABVD + 30(+6)-Gy INRT | 3 y, 95.5 (92.5-97.3) | 3 y, 99.7 (97.7-100) | HL, unknown (<1 each) | 1.2 (NR) | NR | |||
| PET-2+, 192† | 4×ABVD + 30(+6)-Gy INRT | 77.4 (70-4-82.9) | 89.3 (83.4-93.2) | HL, SN (<1 each) | 2.1 (NR) | NR | |||
| PET-2+, 169† | 2×ABVD + 2×BEACOPPesc + 30(+6)-Gy INRT | 90.6 (84.7-94.3) | 96.0 (91.1-98.2) | HL (6), SN (<1), toxicity of second line (<1) | 2.4 (NR) | NR | |||
| PET-3−, 211 | 3×ABVD + 30-Gy IFRT | 90.8 (86.9-94.8) | 99.0 (97.6-100) | HL (0.9) | NR | NR | |||
| PET-3+, 145 | 4×ABVD + 30-Gy IFRT | 87.6 (NR) | 95.5 (NR) | HL (3.4) | NR | NR | |||
Lower RT dose administered in case of complete or partial response after systemic therapy.
b, baseline; CVasc, cardiovascular; esc, escalated; FFDP, freedom from disease progression; NR, not reported; SIR, standardized incidence ratio.
Treated without PET stratification after safety amendment of the H10 trial.
Including 97 patients with early-stage favorable disease.