2347 - Preoperative Radiotherapy with Anlotinib or Apatinib and Disease-Free Survival for Locally Advanced Soft Tissue Sarcoma: Results of Prospective Phase II Clinical Trials
Presenter(s)
N. N. Lu1, L. B. Xu2, Z. G. Zhao2, X. X. Zhang2, Z. Y. Yang3, Q. Chang4, L. Q. Wang5, M. Li6, L. H. Gong7, L. Li8, T. Yu1, S. Hu9, W. F. Liu10, F. J. Yang10, J. Y. Wang11, Y. X. Li12, S. L. Wang12, Q. Zhang13, and S. J. Yu2; 1Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 2Department of Orthopedics, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, Beijing, China, 3Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, 4Department of Ultrasonography, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, Beijing, China, 5Department of Orthopedics, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China., Beijing, China, 6Department of Diagnostic Imaging, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, Beijing, China, 7Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China., Beijing, China, 8Department of Pathology. JiShuiTan Hospital, Beijing, China, 9Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 10Department of Orthopedics, JiShuiTan Hospital, Beijing, China, 11Department of Medical Oncology. National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, Beijing, China, 12Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China., Beijing, China, Beijing, China, 13Department of Orthopedics. JiShuiTan Hospital., Beijing, China
Purpose/Objective(s): To investigate whether the addition of tyrosine-kinase inhibitor (TKI) to preoperative RT will improve the disease-free survival (DFS) rate for patients with locally advanced soft tissue sarcomas (LA-STSs).
Materials/Methods:
Three prospective studies enrolling extremity and trunk LA-STSs were analyzed. The TKI group employed concurrent Anlotinib or Apatinib. The non-TKI group utilized concurrent PARP inhibitor or RT alone. Both 50Gy/25f (CF-RT) and 43.5Gy/15f (MF-RT) was considered as standard RT regimen. The study endpoint was defined as survivals, MWCs, QOL (SF-36) and limb function (MSTS and TESS), respectively.Results:
In total, 269 patients were screened and 167 patients were enrolled for final analysis. All completed planned RT. There’re 81 and 86 patients in the non-TKI (54 with PARPi and 27 with RT alone) group and TKI group, respectively. Patients were well balanced between two groups, except more lower extremities (LE) (72.8% vs. 58.1%) in non-TKI group. Grade = 3 acute toxicity was observed in 29.4% and 15.3% of patients in the TKI and non-TKI groups, respectively, most of which were attributed to concurrent drugs. Except for 12 patients with no further surgery for patients’ refusal (9 all with TKI) or disease progression (3 all with non-TKI), 155 patients underwent surgery, with 152 having limb-conserving surgery and 3 having amputation. The MWCs rate for whole group, non-TKI group and TKI group was 23.7%, 26.3% and 21.1%, respectively. Late toxicities were rare, only 1.8% G3 fibrosis, 0.9% G3 joint stiffness and 1 patient having non-healing fistula; non-significant between two groups. With a median follow-up time of 18.4 (3.4-30.2) months in the non-TKI group and 37.2 (3–63.6) months in the TKI group, the 2-year OS, LC, DMFS, DFS and LSS were 90.5%, 88.1%, 80.4%, 77.1% and 94.7% in the non-TKI group and 97.1%, 93.4%, 90.7%, 86.0% (p=0.052) and 97.1% in the TKI group. Treatment with TKI reduced disease relapses in most subtypes excluding well-differentiated liposarcoma (WDLS) (2-y DFS: 84.1% vs. 73.9%, P=0.049). This DFS improvement was further amplified in the subset of patients with G2-3 tumors =5 cm (2-y DFS: 82.7% vs. 65.8%, P=0.027). Multivariate analysis showed that R1 resection (HR=15.02, p<0.001), G2-3 tumor =5 cm (HR=8.72, p=0.003) and non-TKI (HR=4.58, p=0.032) affected negatively DFS. Due to more LE tumors and more patients undergoing MF-RT with PARPi, the non-TKI group had a worse change in both the MSTS score (P = 0.0008) and SF-36 body pain domain scores (P = 0.011), although worse but no statistical significance observed in TESS (p=0.118) and SF-36 role physical (p=0.224) scores. Among only patients with LE tumors, the differences in MSTS (p=0.0032) and SF-36 pain scores (p=0.031) between two groups were still statistically significant.Conclusion:
Preoperative RT with or without TKI/PARPi enabled good survivals in most LA-STSs with similar MWC rates. Adding TKIs improved DFS, particularly in non-WDLS subtypes. Randomized trials are needed for confirmation.