Clinical study of apatinib in the treatment of stage IV osteogenic sarcoma after failure of chemotherapy

Zhichao Liao; Ting Li; Chao Zhang; Xinyue Liu; Ruwei Xing; Sheng Teng; Yun Yang; Gang Zhao; Xu Bai; Jun Zhao; Jilong Yang

doi:10.20892/j.issn.2095-3941.2019.0397

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Figure 1
Patient inclusion and exclusion flow chart.
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Figure 2
Maximum and whole-course changes in sizes of target lesions vs. baseline after apatinib treatment of stage IV osteogenic sarcoma that did not respond to chemotherapy. (A) Maximum changes in sizes of target lesions vs. baseline after apatinib treatment of stage IV osteogenic sarcoma that did not respond to chemotherapy. (B) Whole-course changes in sizes of target lesions vs. baseline after apatinib treatment for stage IV osteogenic sarcoma that did not respond to chemotherapy.
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Figure 3
Efficacy and toxicity of apatinib in stage IV oesteogenic sarcoma. (A) Overall responses of 33 patients with stage IV osteogenic sarcoma treated with apatinib. Among 33 patients, 31 had measurable lesions, and 2 patients had unmeasurable lesions. Responses at 12 weeks were PR in 2 (6.06%, 2/33), SD in 24 (72.73%, 24/33), and PD in 7 (21.21%, 7/33). (B) PFS after apatinib treatment of stage IV osteogenic sarcoma that did not respond to chemotherapy (mPFS: 7.89 months). (C) OS after apatinib treatment of stage IV osteogenic sarcoma that did not respond to chemotherapy (mOS: 17.61 months). (D) Frequencies and grades of adverse events to apatinib.
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Figure 4
Comparison of imaging findings between 2 patients treated with apatinib for stage IV osteogenic sarcoma that did not respond to chemotherapy. (A-F) Efficacy in patients who were diagnosed with stage IV osteosarcoma at the first visit and received apatinib after they did not respond to first-line chemotherapy. (A, C, E) Imaging findings before treatment with apatinib (January 23, 2017). (B, D, F) Positron emission tomography-CT showed significant decreases in the sizes and metabolic activity of the tumors after treatment with apatinib (April 10, 2017). (G-H) Effects of apatinib in patients with metastatic Ewing’s sarcoma in the lungs who did not respond to first-line chemotherapy. (G) CT images of the chest before treatment with apatinib (May 25, 2017). (H) The lesions in the lungs remained stable from initiation of oral use of apatinib on May 25, 2017 to re-examination on November 24, 2017.

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Table 1

Recent clinical trial for advanced osteosarcoma or bone sarcoma

	Year	Cases	mPFS (month)	mOS (month)	ORR	DCR
Pazopanib¹⁰	2019	18	–	–	0	27.8% (7/18)
Regorafenib¹¹	2019	22	3.6	11.1	13.6% (3/22)	–
Apatinib¹²	2019	37	4.5	9.9	43.2% (16/37)	–
Lenvatinib¹³	2018	26	3.4	–	7.7% (2/26)	–
Cabozantinib¹⁴	2018	42	6.2	–	11.9% (5/42)	–
Apatinib¹⁵	2018	10	7.5	14	20.0% (2/10)	70.0% (7/10)
Sorafenib¹⁶	2012	35	4	7	8.6% (3/35)	48.6% (17/35)

mPFS, median progression-free survival; mOS, median overall survival; ORR, objective response rate; DCR, disease control rate.

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Table 2

Clinical characteristics of stage IV osteogenic sarcoma patients who did not respond to chemotherapy and were treated with apatinib

Characteristics	Value
Gender
Male	23/34 (67.6%)
Female	11/34 (32.4%)
Age, years
Average	35.24
Range	11–73
Distribution
≤ 42	21/34 (61.8%)
> 42	13/34 (38.2%)
ECOG score
0	2/34 (5.9%)
1	17/34 (50%)
2	14/34 (41.2%)
3	1/34 (2.9%)
Subtype (%)
Osteosarcoma	18/34 (52.9%)
EWS/PNET	7/34 (20.6%)
Bone UPS	4/34 (11.8%)
Chondrosarcoma	3/34 (8.8%)
Chordoma	2/34 (5.9%)
Metastatic site
Lung	34/34 (100%)
Lung and others	8/34 (23.5%)

ECOG, Eastern Cooperative Oncology Group; EWS/PNET, Ewing’s sarcoma/primitive neuroectodermal tumor; UPS, undifferentiated pleomorphic sarcoma.

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Table 3

Efficacy of apatinib for stage IV osteogenic sarcoma that did not respond to chemotherapy

Outcome	12-week efficacy analysis*	Final efficacy analysis**
CR	0	0
PR	2	0
Osteosarcoma	1	0
Bone UPS	1	0
SD	24	6
Osteosarcoma	14	3
EWS/PNET	5	1
Bone UPS	2	2
Chondrosarcoma	1	0
Chordoma	2	0
PD	7	27
Osteosarcoma	3	15
EWS/PNET	2	6
Bone UPS	1	2
Chondrosarcoma	1	2
Chordoma	0	2
Excluded case	1 (chondrosarcoma)	1 (chondrosarcoma)
ORR	6.06% (2/33)	0
DCR	78.79% (26/33)	18.18% (6/33)
	PFR_12W = 82%	mPFS = 7.89 m
	OSR_12W = 100%	mOS = 17.61 m

CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate; PFR, progression free survival rate; mPFS, median progression-free survival; OSR, overall survival rate; mOS, median overall survival. *Fisher’s exact test = 0.761, **Fisher’s exact test = 0.589.

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Table 4

Adverse events of apatinib in the treatment of stage IV osteogenic sarcoma that did not respond to chemotherapy

Adverse event*	Grade 1	Grade 2	Grade 3	Total
Hand-foot syndrome	8	4	0	12 (35.29%)
Proteinuria	9	1	1	11 (32.35%)
Hypertension	8	3	0	11 (32.35%)
Mucositis	3	1	0	4 (11.76%)
Fatigue	3	1	0	4 (11.76%)
Anemia	4	0	0	4 (11.76%)
Transaminase increase	4	0	0	4 (11.76%)
Hiccups	4	0	0	4 (11.76%)
Pain	0	3	0	3 (8.82%)
Diarrhea	3	0	0	3 (8.82%)
Skin pigmentation	3	0	0	3 (8.82%)
Periodontal disease	3	0	0	3 (8.82%)
Rash	3	0	0	3 (8.82%)
Bilirubin increase	3	0	0	3 (8.82%)
Pneumothorax	2	0	0	2 (5.88%)
Dysgeusia	0	0	1	1 (2.94%)
Apositia	0	1	0	1 (2.94%)
Hematuria	1	0	0	1 (2.94%)
Dyspnea	1	0	0	1 (2.94%)
Total	62	14	2	78