Efficacy and Adverse Events of Apatinib Salvage Treatment for Refractory Diffuse Malignant Peritoneal Mesothelioma: A Pilot Study

Our plain-English summary of Efficacy and Adverse Events of Apatinib Salvage Treatment for Refractory Diffuse Malignant Peritoneal Mesothelioma: A Pilot Study, by Z.R. Yang, Y.D. Su, R. Ma, et al (Frontiers in Oncology, 2022).

The study

• Authors: Z.R. Yang, Y.D. Su, R. Ma, H.L. Wu, Y. Li
• Journal: Frontiers in Oncology
• Published: 2022;12:811800
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: To investigate the clinical efficacy and adverse events (AEs) of apatinib salvage treatment for diffuse malignant peritoneal mesothelioma (DMPM) that has failed to respond to the recommended treatments.

Methods: 27 patients with refractory DMPM were treated with apatinib at our center from April 2014 to October 2020, at the initial dose of 250 mg/d. The dose was reduced to 125 mg/d when serious adverse events (SAEs) occurred. 28-day was set as a treatment cycle. The frequency of follow up was once every 28 days. The efficacy evaluation was conducted according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and the serum tumor markers before and after apatinib treatment. The safety assessment was performed with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the secondary endpoints were AEs.

Results: The 27 patients completed a median treatment-cycle of 15.0, ranging from 5.1 to 39.4 cycles. At the median follow-up of 14.3 (4.8-51.8) months, median overall survival (OS) was 59.4 months, median apatinib-treatment-related survival (ATRS) was 14.0 (4.8-36.8) months. Complete response (CR) was observed in 0 case (0.0%), partial response (PR) in 4 cases (14.8%), stable disease (SD) in 12 cases (44.4%), and progression disease (PD) in 11 cases (40.7%). The ORR was 14.8%, and DCR was 59.3%. The median serum CA125 values before and after apatinib treatment were 32.9 (7.0-4592.4) U/mL and 29.7 (6.1-4327.4) U/mL, respectively (P=0.009). The common AEs were hypertension (6/27; 22.2%), hand-foot syndrome (5/27; 18.5%), albuminuria (4/27; 14.8%), anemia (4/27; 14.8%), leukopenia (4/27; 14.8%), rash (2/27; 7.4%), fatigue (2/27; 7.4%), oral ulcers (2/27; 7.4%), hoarseness (2/27; 7.4%), nausea/vomiting (2/27; 7.4%), diarrhea (2/27; 7.4%), headache (1/27; 3.7%), and fever (1/27; 3.7%). The incidence rate of grade III/IV AEs was 16.2%.

Conclusions: Apatinib is effective in treating refractory DMPM, with promising efficacy and acceptable safety.

Copyright © 2022 Yang, Su, Ma, Wu and Li.

In plain English

This pilot study, from one center in Beijing, China, looked at 27 patients with diffuse malignant peritoneal mesothelioma (DMPM, a cancer of the abdominal lining) whose disease had not responded to recommended treatments. Between April 2014 and October 2020 they took the oral drug apatinib, starting at 250 mg a day and lowered to 125 mg a day when serious side effects occurred. Three of the 27 patients (11.1%) had a history of asbestos exposure. On scans, no patient's tumors disappeared. Tumors shrank in 4 patients (14.8%), stayed stable in 12 (44.4%) and grew in 11 (40.7%), a disease control rate of 59.3%. The blood marker CA125 fell slightly, from a median of 32.9 to 29.7 U/mL (P=0.009). Two other markers did not change significantly. Nine patients died during follow-up. The most common side effects were high blood pressure (6 of 27) and hand-foot syndrome (5 of 27). The authors reported a 16.2% rate of grade III or IV side effects and no fatal ones. The authors concluded that apatinib could be effective for the epithelioid type of DMPM. They noted that the small sample size limits the strength of the evidence.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-center pilot study in which all patients received apatinib salvage treatment; no comparison group is described
• Who was studied: 27 patients with refractory diffuse malignant peritoneal mesothelioma treated at the Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, China, from April 2014 to October 2020. There were 10 males and 17 females with a median age of 56 (range 24-77). By tumor type, 24 were epithelioid, 2 biphasic and 1 sarcomatoid. 3 (11.1%) had a history of asbestos exposure.
• Exposure: Oral apatinib (a drug that targets VEGFR-2), 250 mg daily, reduced to 125 mg daily when serious adverse events occurred, in 28-day cycles. Asbestos exposure was not studied; only the number of patients with an exposure history is reported.
• Main results:
  • Among the 27 patients, there were no complete responses. 4 (14.8%) had a partial response, 12 (44.4%) stable disease and 11 (40.7%) progressive disease. The objective response rate was 14.8% and the disease control rate was 59.3%.
  • Median serum CA125 was 32.9 (7.0-4592.4) U/mL before apatinib and 29.7 (6.1-4327.4) U/mL after (P=0.009).
  • The changes in CA199 (P=0.499) and CEA (P=0.085) before versus after treatment were not statistically significant.
  • At a median follow-up of 14.3 months, 9 of the 27 patients (33.3%) had died and 18 (66.7%) were alive. Median overall survival, counted from diagnosis, was 59.4 months. Median survival counted from the start of apatinib was 14.0 months.
  • Overall survival did not differ significantly between patients with and without prior CRS+HIPEC (cytoreductive surgery plus heated chemotherapy in the abdomen), or between those with and without prior chemotherapy.
  • The most common adverse events were hypertension (6/27; 22.2%) and hand-foot syndrome (5/27; 18.5%). Albuminuria, anemia and leukopenia each occurred in 4/27 (14.8%).
  • The incidence rate of grade III/IV adverse events was 16.2%. There were no grade V (fatal) adverse events.
  • One example patient, a 55-year-old woman with epithelioid DMPM, started apatinib in May 2018 as third-line treatment. Her disease remained stable at follow-up in June 2021.
• The authors' conclusion: The authors concluded that apatinib could be effective for epithelioid DMPM. Their abstract states that it is effective in refractory DMPM with acceptable safety.
• Limitations the authors state:
  • The small sample size of this pilot study limits the strength of the evidence.
  • The study only suggests effectiveness for epithelioid DMPM; the biphasic and sarcomatoid types need further study.
  • Other treatment patterns and the molecular mechanisms need further investigation.

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Tumor Marker, Median Overall Survival, Incidence.

Related studies

• Apatinib for salvage treatment of advanced malignant pleural mesothelioma: A case report — Z. Du, Y. Yu, et al. (2018)
• Expert guidance on prophylaxis and treatment of dermatologic adverse events with Tumor Treating Fields (TTFields) therapy in the thoracic region — M.J. Anadkat, M. Lacouture, et al. (2022)
• Apatinib Mesylate Inhibits the Proliferation and Metastasis of Epithelioid Malignant Peritoneal Mesothelioma In Vitro and In Vivo — Z.R. Yang, Z.G. Chen, et al. (2020)
• Analysis on the efficacy and safety of chemotherapy combined with or without bevacizumab after CRS+HIPEC in patients with malignant peritoneal mesothelioma: a single-center retrospective study — Z.R. Yang, X.L. Liang, et al. (2026)
• Lurbinectedin in Refractory Diffuse Malignant Peritoneal Mesothelioma: Report of Two Cases — L. Gros, P. Szturz, et al. (2021)
• Prevention and Management of Dermatologic Adverse Events Associated With Tumor Treating Fields in Patients With Glioblastoma — M.E. Lacouture, M.J. Anadkat, et al. (2020)

Browse more research in Frontiers in Oncology, or return to medical research.