Apatinib Plus Pegylated Liposomal Doxorubicin vs Pegylated Liposomal Doxorubicin Alone for Platinum-Resistant Recurrent Ovarian Cancer
abstract
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There are substantial unmet therapeutic needs in patients with platinum-resistant recurrent ovarian cancer (PROC), and novel therapeutic strategies should be explored.
Objective
To evaluate the efficacy and safety of treatment with apatinib (a vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor) plus pegylated liposomal doxorubicin (PLD) for PROC.
Design, Setting, and Participants
The APPROVE trial was performed as an open-label, randomized clinical trial at 11 hospitals in China between March 22, 2018, and November 16, 2020. Patients with histologically confirmed ovarian cancer who had experienced disease progression during or within 6 months of discontinuing any prior line of treatment with platinum-based chemotherapy were eligible. This primary analysis was based on data that were current as of January 28, 2021.
Interventions
Patients received PLD alone (40 mg/m2, intravenously, every 4 weeks, for up to 6 cycles) or PLD plus apatinib (250 mg, orally, daily).
Main Outcomes and Measures
The primary end point was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1, in the intent-to-treat population.
Results
In total, 152 female patients were randomized, with 78 (51.3%) in the apatinib plus PLD group (median age, 54 years; range, 22-76 years) and 74 (48.7%) in the PLD group (median age, 56 years; range, 33-72 years). The median follow-up duration was 8.7 months (IQR, 4.7-14.1 months). The median PFS was 5.8 months (95% CI, 3.8-8.8) for treatment with apatinib plus PLD vs 3.3 months (95% CI, 2.1-3.8) for PLD (hazard ratio, 0.44; 95% CI, 0.28-0.71; P < .001). The median overall survival was 23.0 months (95% CI, 18.9 to not reached) with treatment with apatinib plus PLD vs 14.4 months (95% CI, 12.1-23.4) with PLD (hazard ratio, 0.66; 95% CI, 0.40-1.09). The most frequent grade 3 or higher treatment-emergent adverse events were decreased neutrophil counts (11 [14.9%] in the apatinib plus PLD group vs 6 [8.3%] in the PLD group), hypertension (6 [8.1%] vs none), and decreased white blood cell count (5 [6.8%] vs 3 [4.2%]). Two patients receiving treatment with apatinib plus PLD experienced grade 2 fistulas.
Conclusions and Relevance
This randomized clinical trial found that treatment with apatinib plus PLD showed promising efficacy and manageable toxic effects in patients with PROC and may be a new alternative treatment option in this setting.
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Additional Info
Disclosure statements are available on the authors' profiles:
Effect of Apatinib Plus Pegylated Liposomal Doxorubicin vs Pegylated Liposomal Doxorubicin Alone on Platinum-Resistant Recurrent Ovarian Cancer: The APPROVE Randomized Clinical Trial
JAMA Oncol 2022 Jun 30;[EPub Ahead of Print], T Wang, J Tang, H Yang, R Yin, J Zhang, Q Zhou, Z Liu, L Cao, L Li, Y Huang, K Jiang, W Wang, F She, N Guan, Z Hou, N Li, L WuFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Ovarian cancer is the gynecological tumor with the highest mortality rate. After surgery and adjuvant therapy, more than 50% of patients will relapse and develop platinum resistance. In this setting, monotherapy with pegylated liposomal doxorubicin (PLD), docetaxel, paclitaxel, or topotecan is the recommended option; however, this has only a short-term effect.
As angiogenesis plays a role in ovarian physiology and the progression of ovarian cancer during metastatic spread and its inhibition has been proven to have clinical benefit, apatinib, an oral small-molecule tyrosine kinase inhibitor that selectively binds to and inhibits VEGF receptor 2, was combined with PLD. A total of 152 patients with disease progression during or within 6 months of any prior line of treatment with platinum-based chemotherapy were randomized to receive PLD alone (40 mg/m2, intravenously, every 4 weeks, for up to six cycles) or PLD plus apatinib (250 mg daily).
The median progression-free survival (PFS) was 5.8 months for treatment with apatinib plus PLD versus 3.3 months with PLD alone (HR, 0.44; P < .001). The median overall survival (OS) was 23.0 months with apatinib plus PLD versus 14.4 months with PLD alone (HR, 0.66).
Grade 3 or higher adverse events presented as decreased neutrophil counts (11 [14.9%] in the apatinib plus PLD group vs 6 [8.3%] in the PLD group), hypertension (6 [8.1%] vs none), and decreased white blood cell counts (5 [6.8%] vs 3 [4.2%]).
Conclusion: Patients receiving apatinib combined with PLD had improved PFS and OS, with manageable side effects. Therefore, this combination may offer an alternative option for patients with platinum-resistant ovarian cancer, and, in contrast to bevacizumab, apatinib can be administered orally.