MedicalResearch.com Interview with:
David S. Siegel, MD, PhD
Chief, Myeloma Division
John Theurer Cancer Center
Hackensack University Medical Center
Hackensack, NJ 07601
MedicalResearch.com: What is the background for this study? What are the main findings?
- We reported results from the prospectively planned final analysis of overall survival (OS) from the Phase 3 ASPIRE trial, an international, randomized study evaluating KYPROLIS (carfilzomib) in combination with lenalidomide and dexamethasone (KRd) versus lenalidomide and dexamethasone alone (Rd) in patients with relapsed or refractory multiple myeloma following treatment with one to three prior regimens. Overall survival was a secondary endpoint in the trial.
- Data published last week in the Journal of Clinical Oncology demonstrated that the addition of KYPROLIS to Rd reduced the risk of death by 21 percent versus Rd alone and extended OS by 7.9 months (median OS 48.3 months for KRd versus 40.4 months for Rd, HR = 0.79, 95 percent CI, 0.67 – 0.95; one-sided p=0.0045).
- Notably, an OS improvement of 11.4 months was observed for patients at first relapse (47.3 versus 35.9 months [HR = 0.81, 95 percent CI, 0.62 – 1.06]), supporting early use of KRd.
- The safety data from ASPIRE was consistent with the known safety profile of KYPROLIS. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were diarrhea, anemia, neutropenia, fatigue, upper respiratory tract infection, pyrexia, cough, hypokalemia, thrombocytopenia, muscle spasms, pneumonia, nasopharyngitis, nausea, constipation, insomnia and bronchitis.
MedicalResearch.com: What should readers take away from your report?
- Based on these data, KRd should be considered a preferred treatment option in relapsed or refractory multiple myeloma.
- In addition, KRd is a highly effective therapy for patients at first relapse, which should be reflected in future treatment algorithms.
- Lastly, ASPIRE is the second Phase 3 trial in patients with relapsed or refractory multiple myeloma to demonstrate a statistically significant OS advantage for a KYPROLIS-based therapy against a recent standard of care.
- The first Phase 3 study was ENDEAVOR, a head-to-head comparison of two proteasome inhibitors (KYPROLIS and Velcade [bortezomib]). ENDEAVOR demonstrated that patients who received KYPROLIS and dexamethasone (Kd) had a statistically significant and clinically meaningful OS improvement versus those who received Velcade and dexamethasone (Vd) (median OS 47.6 for Kd versus 40.0 months for Vd, HR = 0.79, 95 percent CI, 0.65 – 0.96; one-sided p= .010).
- Taken together, the OS results from ASPIRE and ENDEAVOR support the importance of proteasome inhibition with KYPROLIS for relapsed or refractory multiple myeloma.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
- Studies evaluating other modern therapies are ongoing, with OS data not yet mature. Those results will provide additional information regarding the clinical benefit of other modern therapies for relapsed or refractory multiple myeloma.
- We have not yet seen combinations of carfilzomib with daratumumab or with i/o assets such as the checkpoint inhibitors.
Disclosures: I’ve listed my disclosures below.
o Speakers’ Bureau: Celgene, Amgen, Janssen Oncology, Takeda Pharmaceuticals, Bristol-Myers Squibb
Citations: DOI: 10.1200/JCO.2017.76.5032 Journal of Clinical Oncology – published online before print January 17, 2018
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