Abstract:
Background: Retrospective studies have suggested the potential of apatinib, an anti-angiogenesis tyrosine kinase inhibitor, plus ifosfamide and etoposide (IE) over IE in advanced osteosarcoma. This trial aimed to further compared apatinib plus IE versus IE alone in patients with advanced osteosarcomas post first-line chemotherapy failure.
Methods: In this multicenter, randomized controlled trial (OAIE/PKUPH-sarcoma 11), patients with histologically confirmed osteosarcoma, progressing after at least one prior line of chemotherapy, were randomized (2:1) to either apatinib plus IE or IE alone. The apatinib plus IE group received oral apatinib 500mg daily along with ifosfamide (1.8 g/m2/d) and etoposide (100 mg/m2/d) on days 1-3, every 3 weeks. The IE group received IE on days 1-5, every 3 weeks. Apatinib continued for a maximum of one year, and IE was administered for up to 10 cycles. The primary endpoint was progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1.
Results: A total of 81 patients were enrolled, with 53(65.4%) receiving apatinib and IE, while 28(34.6%) were treated with IE alone. The median follow-up period was 9.5 (95%CI?) months. The apatinib plus IE group showed a median PFS of 5.5 months (95% confidence interval [CI], 4.0 to 6.4), compared to 3.9 months (95% CI, 1.6 to 4.6) in the IE group, yielding a hazard ratio of 0.43 (95% CI, 0.25 to 0.75), P=0.0023. Objective response rates were 20.8% (95% CI, 10.8 to 34.1) for the apatinib plus IE group and 21.4% (95% CI, 8.3 to 41.0) for the IE group. Disease control rates were numerically higher in the apatinib plus IE group at 79.2% (95% CI, 65.9 to 89.2), compared to 53.6% (95% CI, 33.9 to 72.5) in the IE group. The median time to response was 1.3 months (95% CI, 1.1 to 2.6) for the apatinib plus IE group and 1.5 months (95% CI, 1.3 to not estimated [NE]) for the IE group. Duration of response also favored the apatinib plus IE group, with a median of 6.1 months (95% CI, 1.9 to 8.0) compared to 4.1 months (95% CI, 1.7 to NE) in the IE group. The median overall survival has not yet been reached in either group. Grade 3-4 treatment-related adverse events occurred in 71.2% of patients in the apatinib plus IE group and 62.1% in the IE group, with the most common events being white blood cell count decreased, anemia, and neutrophil count decreased.
Conclusions: Apatinib plus IE demonstrated a significant improvement in PFS in patients with advanced osteosarcomas, with an acceptable safety profile.
Table. Efficacy endpoints
| Endpoints | Apatinib+IE (n=53) | IE (n=28) |
| PFS, months, median, 95%CI | 5.5 (4.0-6.4) | 3.9 (1.6-4.6) |
| HR (95%CI) | 0.43 (0.25, 0.75) | |
| P | 0.0023 | |
| ORR, n, %, 95%CI | 11 (20.8) (10.8, 34.1) | 6 (21.4) (8.3, 41.0) |
| DCR, n, %, 95%CI | 42 (79.2) (65.9, 89.2) | 15 (53.6) (33.9, 72.5) |
| TTR, months, median, 95%CI | 1.3 (1.1-2.6) | 1.5 (1.3-NE) |
| DOR, months, median, 95%CI | 6.1 (1.9-8.0) | 4.1 (1.7-NE) |
Abstract:
In recent years, the molecular genetic mechanisms of bone and soft tissue tumors have been gradually revealed. As a result, opportunities have arisen for chemotherapies that are tailored to the genetic abnormalities and mutations of each histologic subtype of sarcoma. These chemotherapies are expected to serve not only as chemotherapy for advanced cases but also as neoadjuvant chemotherapy to facilitate surgery. In this lecture, I will present cases with an intermediate malignant or malignant bone and soft tissue tumor who were successfully treated with histology-tailored neoadjuvant chemotherapy and surgery, based on molecular biological findings.
Abstract:
Systemic cytotoxic agents remain the cornerstone of soft tissue sarcoma(STS) tr eatment. However, the advent of molecularly guided therapies marks a new era in STS management. Dermatofibrosarcoma protuberans, characterized by the pathognomonic COL1A1::PDGFB fusion gene, responds well to imatinib, which inhibits the PDGF-PDGFR signaling axis. Inflammatory myofibroblastic tumors exhibit distinct gene fusions with ALK, ROS1, and NTRK, and their respective targeted therapies demonstrated successful outcomes. Epithelioid sarcoma, defined by the loss of INI-1/SMARCB1 protein, shows sensitivity to the EZH2 inhibitor tazemetostat in advanced stage patients. Additionally, the aberrant activation of the mammalian target of rapamycin (mTOR) pathway in perivascular epithelioid cell tumors (PEComa) has been addressed through mTOR inhibitors like sirolimus and everolimus. The AMPECT study further substantiates the efficacy of nab-sirolimus, a nanoparticle, albumin-bound, intravenously administered sirolimus, providing excellent outcomes for malignant PEComa patients. This lecture will delve into these molecularly targeted approaches, highlighting their clinical implications and integration into contemporary STS treatment paradigms
Tom Wei-Wu Chen, MD
Attending physician
Department of Oncology
National Taiwan University Hospital
Taipei, Taiwan
Dr. Tom W. Chen is currently an attending physician at the Department of Oncology, National Taiwan University Hospital (NTUH) in Taipei, Taiwan. Dr. Chen received internal medicine training followed by a fellowship course as a medical oncologist in NTUH. Afterwards, he joined Drug Development Program (DDP) in Princess Margaret Cancer Centre in Toronto, Canada as a clinical fellow to study early phase clinical trials with Dr. Lillian Siu and Dr. Phil Bedard. During his stay in Princess Margaret, he gained more experience with next-generation sequencing and precision medicine, as well as interest in sarcoma patients.
