Combo demonstrates superior PFS in relapsed MM

Cancer patient receives therapy

Photo by Rhoda Baer

Interim results of the phase 3 ENDEAVOR trial suggest that carfilzomib given in combination with low-dose dexamethasone may be more effective than bortezomib plus low-dose dexamethasone for certain patients with relapsed multiple myeloma (MM).

Patients who received the carfilzomib combination had a higher overall response rate and nearly twice the median progression-free survival (PFS) of patients who received the bortezomib combination.

Those who received carfilzomib had higher rates of cardiac and renal failure but lower rates of neuropathy. And rates of treatment discontinuation and on-study death were similar between the treatment arms.

Onyx Pharmaceuticals, the company developing carfilzomib (as Kyprolis), announced these results yesterday. The company plans to submit complete trial data for presentation at the 2015 ASCO Annual Meeting.

The ENDEAVOR trial included 929 MM patients who had relapsed after at least 1, but not more than 3, prior treatment regimens. They were randomized to receive carfilzomib or bortezomib, both in combination with low-dose dexamethasone.

Patients received carfilzomib as a 30-minute infusion, along with low-dose dexamethasone (20 mg). For cycle 1 only, carfilzomib was given at 20 mg/m² on days 1 and 2, followed by escalation to 56 mg/m² on days 8, 9, 15, and 16. Patients who tolerated 56 mg/m² in cycle 1 remained at this dose for subsequent cycles on days 1, 2, 8, 9, 15, and 16 on a 28-day cycle.

Patients who received bortezomib (1.3 mg/m²) with low-dose dexamethasone (20 mg) received bortezomib subcutaneously or intravenously at the discretion of the investigator and in accordance with the regulatory approval of bortezomib. More than 75% of the patients in the control arm received bortezomib subcutaneously.

The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death. The median PFS in the carfilzomib arm was roughly double that of the bortezomib arm—18.7 months and 9.4 months, respectively (hazard ratio=0.53).

The carfilzomib combination also demonstrated superiority over the bortezomib combination for secondary endpoints of higher overall response rate and lower neuropathy events.

However, the rates for cardiac and renal failure were higher in the carfilzomib arm than the bortezomib arm. The same was true for hypertension and dyspnea.

Rates of cardiac and renal failure with carfilzomib in this trial were similar to those observed in the phase 3 ASPIRE trial, but rates of hypertension and dyspnea were higher in ENDEAVOR than ASPIRE.

Cancer patient receives therapy

Photo by Rhoda Baer

Interim results of the phase 3 ENDEAVOR trial suggest that carfilzomib given in combination with low-dose dexamethasone may be more effective than bortezomib plus low-dose dexamethasone for certain patients with relapsed multiple myeloma (MM).

Patients who received the carfilzomib combination had a higher overall response rate and nearly twice the median progression-free survival (PFS) of patients who received the bortezomib combination.

Those who received carfilzomib had higher rates of cardiac and renal failure but lower rates of neuropathy. And rates of treatment discontinuation and on-study death were similar between the treatment arms.

Onyx Pharmaceuticals, the company developing carfilzomib (as Kyprolis), announced these results yesterday. The company plans to submit complete trial data for presentation at the 2015 ASCO Annual Meeting.

The ENDEAVOR trial included 929 MM patients who had relapsed after at least 1, but not more than 3, prior treatment regimens. They were randomized to receive carfilzomib or bortezomib, both in combination with low-dose dexamethasone.

Patients received carfilzomib as a 30-minute infusion, along with low-dose dexamethasone (20 mg). For cycle 1 only, carfilzomib was given at 20 mg/m² on days 1 and 2, followed by escalation to 56 mg/m² on days 8, 9, 15, and 16. Patients who tolerated 56 mg/m² in cycle 1 remained at this dose for subsequent cycles on days 1, 2, 8, 9, 15, and 16 on a 28-day cycle.

Patients who received bortezomib (1.3 mg/m²) with low-dose dexamethasone (20 mg) received bortezomib subcutaneously or intravenously at the discretion of the investigator and in accordance with the regulatory approval of bortezomib. More than 75% of the patients in the control arm received bortezomib subcutaneously.

The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death. The median PFS in the carfilzomib arm was roughly double that of the bortezomib arm—18.7 months and 9.4 months, respectively (hazard ratio=0.53).

The carfilzomib combination also demonstrated superiority over the bortezomib combination for secondary endpoints of higher overall response rate and lower neuropathy events.

However, the rates for cardiac and renal failure were higher in the carfilzomib arm than the bortezomib arm. The same was true for hypertension and dyspnea.

Rates of cardiac and renal failure with carfilzomib in this trial were similar to those observed in the phase 3 ASPIRE trial, but rates of hypertension and dyspnea were higher in ENDEAVOR than ASPIRE.

Cancer patient receives therapy

Photo by Rhoda Baer

Interim results of the phase 3 ENDEAVOR trial suggest that carfilzomib given in combination with low-dose dexamethasone may be more effective than bortezomib plus low-dose dexamethasone for certain patients with relapsed multiple myeloma (MM).

Patients who received the carfilzomib combination had a higher overall response rate and nearly twice the median progression-free survival (PFS) of patients who received the bortezomib combination.

Those who received carfilzomib had higher rates of cardiac and renal failure but lower rates of neuropathy. And rates of treatment discontinuation and on-study death were similar between the treatment arms.

Onyx Pharmaceuticals, the company developing carfilzomib (as Kyprolis), announced these results yesterday. The company plans to submit complete trial data for presentation at the 2015 ASCO Annual Meeting.

The ENDEAVOR trial included 929 MM patients who had relapsed after at least 1, but not more than 3, prior treatment regimens. They were randomized to receive carfilzomib or bortezomib, both in combination with low-dose dexamethasone.

Patients received carfilzomib as a 30-minute infusion, along with low-dose dexamethasone (20 mg). For cycle 1 only, carfilzomib was given at 20 mg/m² on days 1 and 2, followed by escalation to 56 mg/m² on days 8, 9, 15, and 16. Patients who tolerated 56 mg/m² in cycle 1 remained at this dose for subsequent cycles on days 1, 2, 8, 9, 15, and 16 on a 28-day cycle.

Patients who received bortezomib (1.3 mg/m²) with low-dose dexamethasone (20 mg) received bortezomib subcutaneously or intravenously at the discretion of the investigator and in accordance with the regulatory approval of bortezomib. More than 75% of the patients in the control arm received bortezomib subcutaneously.

The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death. The median PFS in the carfilzomib arm was roughly double that of the bortezomib arm—18.7 months and 9.4 months, respectively (hazard ratio=0.53).

The carfilzomib combination also demonstrated superiority over the bortezomib combination for secondary endpoints of higher overall response rate and lower neuropathy events.

However, the rates for cardiac and renal failure were higher in the carfilzomib arm than the bortezomib arm. The same was true for hypertension and dyspnea.

Rates of cardiac and renal failure with carfilzomib in this trial were similar to those observed in the phase 3 ASPIRE trial, but rates of hypertension and dyspnea were higher in ENDEAVOR than ASPIRE.