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Pazolimus: pazopanib plus sirolimus following progression on pazopanib, a retrospective case series analysis
1Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. danielakatz@hadassah.org.il.
Background:
To explore the activity of pazopanib (P) + sirolimus (S) in patients who progressed after previous clinical benefit on pazopanib.
Methods:
Eight patients with progressing metastatic high grade soft tissue sarcoma (STS) whose disease advanced on P following a response duration of at least 4 months were offered re-challenge of P supplemented by off-label S and a single patient with progressing metastatic chondrosarcoma was offered the combination as compassionate treatment. Patients were treated in two centers: Hadassah Medical Center and Tel Aviv Medical Center. Patients received oral P 200-600 mg once a day supplemented by S 3-4 mg taken separately, 12 h after the P dose.
Results:
Patients received treatment from December 2012 to February 2016. Four progressed on the combination and their treatment was terminated. Two patients were undergoing treatment when data was summarized. Best Response Evaluation Criteria in Solid Tumour (RECIST) responses were: one partial response (PR), four stable disease (SD), and four progressive disease (PD), corresponding to five PR and four PD on the Choi criteria. Median progression free survival was 5.5 months (range 4-17).
Conclusions:
Our series showed that the combination of P + S has activity in STS patients selected by previous response to P and in a patient with chondrosarcoma, suggesting this can serve as a mechanism to reverse resistance to P and extend the chemotherapy-free window.
Insights
Pazopanib plus sirolimus shows activity in patients with advanced soft tissue sarcoma (STS) who previously responded to pazopanib. This combination may help reverse pazopanib resistance and extend treatment-free intervals.
Area of Science:
- Oncology
- Pharmacology
- Medical Research
Background:
- Investigating pazopanib (P) plus sirolimus (S) in patients with metastatic high-grade soft tissue sarcoma (STS) who progressed after prior clinical benefit from pazopanib.
- Focus on patients with advanced STS and a single chondrosarcoma patient who experienced disease progression despite pazopanib treatment.
Purpose of the Study:
- To evaluate the efficacy of re-challenging with pazopanib combined with sirolimus in STS patients.
- To explore the potential of this combination therapy to overcome pazopanib resistance.
Main Methods:
- Eight patients with progressing metastatic STS and one with chondrosarcoma received pazopanib (200-600 mg/day) plus sirolimus (3-4 mg/day) between December 2012 and February 2016.
- Treatment involved oral pazopanib and separately administered sirolimus.
- Tumor response was assessed using RECIST and Choi criteria.
Main Results:
- Best responses included one partial response (PR), four stable disease (SD), and four progressive disease (PD) by RECIST criteria.
- Choi criteria showed five PR and four PD.
- Median progression-free survival was 5.5 months (range 4-17 months).
Conclusions:
- The combination of pazopanib plus sirolimus demonstrated activity in selected STS patients previously responsive to pazopanib.
- This therapeutic approach suggests a potential strategy to reverse pazopanib resistance.
- The combination may help extend chemotherapy-free intervals in patients with advanced STS.
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