Perioperative Therapy for Non-Small Cell Lung Cancer with Immune Checkpoint Inhibitors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Current Status of Perioperative Therapy
3. Initiation of Clinical Trials for Perioperative Therapy by ICI
4. Neoadjuvant vs. Adjuvant
5. Clinical Trials of Neoadjuvant Mono- or Dual ICI Therapy
Registration # | Trial & Stage | Neoadjuvant Therapy | N (Plan) | N (Reported) | Delay of Surgery (%) | Failure to Surgery (%) | R0 Resection (%) | TRAE (≥G3) (%) | MPR (%) | pCR (%) | Survival | Status | Ref |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
NCT02259621 | Johns Hopkins Univ. (p2) IB (>4 cm) to IIIA | nivolumab (twice) | 30 | 22 | 0 | 0 | 95 | Preope: 4.5 | 45 | 15 | Median RFS: NR 18 m RFS: 73% | On going | [31] |
NCT02927301 | LCMC3 (p2) IB to IIIA, IIIB (T3N2, T4 (size)) | atezolizumab (twice) | 180 | 181 | 12 | 12 | 92 | Preope: 6 Postope: 14 | 21 | 7 | 1 y DFS: 85% 1 y OS: 95% | On going | [32] |
NCT02994576 | PRINCEPS (p2) IA (≥2 cm) to IIIA(non-N2) | atezolizumab (once) | 60 | 30 | 0 | 0 | 97 | 0 | 0 | No data | No data | On going | [29] |
NCT03030131 | IONESCO (p2) IB to IIIA | durvalumab (3 times) | 81 | 46 | No data | 0 | 90 | ICI-related: 0 (Death:9) | No data | No data | Median OS/DFS: NR/NR 18 m OS/DFS: 89%/70% | Terminated (mortality *) | [33] |
NCT03158129 | NEOSTAR (p2) I to IIIA | nivolumab (3 times) or nivolumab (3 times) + ipilimumab | 44 | 44 | 22 | Nivo: 4 N + I: 19 | 100 | Nivo: 13 N + I: 10 | Nivo: 22 N + I: 38 | Nivo: 9 N + I: 29 | Median OS/RFS: NR/NR | On going | [30] |
6. Clinical Trials for ICI Combination Therapy with Chemotherapy or Chemoradiotherapy
Registration # | Trial & Stage | Neoadjuvant Therapy | N (Plan) | N (Reported) | Delay of Surgery (%) | Failure to Surgery (%) | R0 Resection (%) | TRAE (≥G3) (%) | MPR (%) | pCR (%) | Survival | Status | Ref |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
NCT02998528 | Checkmate 816 (p3) IB to IIIA | Nivolumab + PT-DC vs. PT-DC | 358 | 358 | 21 vs. 18 | 16 vs. 21 | 83 vs. 78 | G3–4: 19 vs. 21 | 36.9 vs. 8.9 (p < 0.0001) | 24 vs. 2.2 (p < 0.0001) | No data | On going | [35] |
NCT02716038 | Columbia Univ. (p2) IB to IIIA | atezolizumab + CBDCA/Nab-PTX | 30 | 30 | 0 | 3 | 87 | ≥50 | 57 | 33 | Median OS/DFS: NR/17.9 m | On going | [43] |
NCT02572843 | SAKK16/14 (p2) IIIA (pN2) | durvalumab + CDDP/DTX | 68 | 68 | No data | 19 | No data | Any: 88.1 | 60 | 18.2 | Median OS/EFS: NR/NR 1 y EFS: 73.3% | On going | [44] |
NCT03081689 | NADIM (p2) IIIA (pN2) | nivolumab + CBDCA/PTX | 46 | 46 | 0 | 11 | 100 | 30 | 83 | 63 | Median PFS/OS: NR/NR 1 y PFS:95.7% 2 y PFS:77.1% | On going | [36] |
NCT03480230 | American Univ. of Beirut Medical Center (p2) II or IIIA | avelumab + PT-DC | 60 | 15 | No data | 27 | No data | 27 | No data | 9 | Median OS/RFS: NR/NR | Terminated (lower response *) | [45] |
NCT03694236 | Yonsei Univ. (p2) III (N2) | durvalumab + CBDCA/PTX + RT 45 Gy | 39 | 14 | No data | 8 | 100 | 7 | 72.7 | 36.4 | No data | On going | [41] |
7. Identification and Monitoring of MRD
8. New ICI Agents
9. Conclusions and Future Perspectives
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Registration # | Trial | Therapy | N | Pretreatment | Experimental Arm | Control Arm | Primary Endpoint | Stage | Country |
---|---|---|---|---|---|---|---|---|---|
NCT02273375 | BR.31 | ICI mono | 1360 | Yes/No PT-DC | durvalumab 1 year | Placebo | DFS | pIB to IIIA | Global |
NCT02486718 | IMpower010 | ICI mono | 1280 | Yes/No PT-DC | Atezolizumab 1 year | BSC | DFS | pIB to IIIA | Global |
NCT02504372 | PEARLS/KEYNOTE-091 | ICI mono | 1177 | Yes/No PT-DC t | pembrolizumab 1 year | Placebo | DFS | pIB to IIIA | Global |
NCT02595944 | ANVIL | ICI mono | 714 | Yes/No PT-DC | nivolumab 1 year | Observation | DFS/OS | pIB to IIIA | US |
NCT04642469 | MeRmaiD-2 | ICI mono | 284 | Yes/No PT-DC | durvalumab | Placebo | DFS in PD-L1 TC ≥ 1% | II to III without positive EGFR/ALK | Global |
NCT04385368 | MeRmaiD-1 | ICI chemo | 322 | No | durvalumab + standard of care chemotherapy | Placebo + standard of care chemotherapy | DFS | II to III without positive EGFR/ALK | Global |
NCT04564157 | NADIM-ADJUVANT | ICI chemo | 210 | No | Nivolumab + CBDCA/PTX (4 times) Maintenance: nivolumab (6 times) | Nivolumab + CBDCA/PTX (4 times) Maintenance: Observation | DFS | pIB (≥4 cm) to IIIA | Spain |
Registration # | Trial | Therapy | Phase | N | Stage | New Agents (Target) | Experimental Arm | Primary Endpoint | Country |
---|---|---|---|---|---|---|---|---|---|
NCT04205552 | NEOpredict-Lung | ICI dual | 2 | 60 | IB to selected IIIA | relatlimab (Lag-3) | Arm A: nivolumab(twice) Arm B: nivolumab + relatlimab (twice) | Feasibility | Belgium Germany Netherlands |
NCT03794544 | NeoCOAST | ICI dual | 2 | 80 | I (>2 cm) to IIIA (single N2 ≤ 3 cm) | oleclumab (CD73) monalizumab (NKG2A) | Arm A: durvalumab Arm B: durvalumab + oleclumab Arm C: durvalumab + monalizumab Arm D: durvalumab + danvatirsen | MPR | Global (Western Countries) |
NCT04832854 | GO42501 | ICI dual + Chemo | 2 | 82 | II to IIIB(T3N2) | tiragolumab (TIGIT/RVR) | PD-L1 high: Atezolizumab + tiragolumab (4 times) PD-L1 All comers: Atezolizumab + tiragolumab + PT-DC (4 times) | 1. Surgical delays, 2. Complications, 3. Cancellations of surgery, 4. AE, 5. MPR | US Spain Switzerland |
NCT03968419 | CANOPY-N | ICI + IM | 2 | 110 | IB to IIIA (non-N2 nor T4) | canakinumab (IL-1β) | Arm A: canakinumab Arm B: canakinumab + pembrolizumab Arm C: pembrolizumab | MPR | Global |
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Soh, J.; Hamada, A.; Fujino, T.; Mitsudomi, T. Perioperative Therapy for Non-Small Cell Lung Cancer with Immune Checkpoint Inhibitors. Cancers 2021, 13, 4035. https://doi.org/10.3390/cancers13164035
Soh J, Hamada A, Fujino T, Mitsudomi T. Perioperative Therapy for Non-Small Cell Lung Cancer with Immune Checkpoint Inhibitors. Cancers. 2021; 13(16):4035. https://doi.org/10.3390/cancers13164035
Chicago/Turabian StyleSoh, Junichi, Akira Hamada, Toshio Fujino, and Tetsuya Mitsudomi. 2021. "Perioperative Therapy for Non-Small Cell Lung Cancer with Immune Checkpoint Inhibitors" Cancers 13, no. 16: 4035. https://doi.org/10.3390/cancers13164035