[Beacon Staff]

Kyprolis vs. Velcade in relapsed myeloma - trial results

by Beacon Staff on Sun Mar 01, 2015 8:34 pm

Hello everyone,

Amgen just issued a press release this evening with initial results of its Phase 3, head-to-head clinical trial comparing Kyprolis to Velcade in relapsed multiple myeloma.

We're posting the main part of the press release here for everyone to review and comment on. We have not yet reviewed it in detail, so we'll let forum members share their thoughts on it as we also process it.

Phase 3 Head-to-Head ENDEAVOR Study Demonstrates Superiority Of Kyprolis® (Carfilzomib) Over Velcade® (Bortezomib) In Patients With Relapsed Multiple Myeloma

Study Met Primary Endpoint of Progression-Free Survival
Patients Receiving Kyprolis Lived Twice as Long Without Disease Progression

Amgen (NASDAQ: AMGN) and its subsidiary Onyx Pharmaceuticals, Inc., today announced the results from a planned interim analysis showing that the Phase 3 head-to-head clinical trial ENDEAVOR evaluating Kyprolis® (carfilzomib) for Injection in combination with low-dose dexa­meth­a­sone versus Velcade® (bortezomib) and low-dose dexa­meth­a­sone met the primary endpoint of progression-free survival (PFS). Patients with relapsed multiple myeloma treated with Kyprolis lived twice as long without their disease worsening, demonstrating statistically and clinically significant superiority over Velcade (median PFS 18.7 months versus 9.4 months, HR=0.53, 95 percent CI, 0.44 – 0.65).

The Kyprolis combination demonstrated superiority over the Velcade combination for secondary objectives of higher overall response rate and lower neuropathy events. Overall survival data are not yet mature and continue to be monitored.

Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. The rates of cardiac failure and renal failure for Kyprolis were comparable to those observed in the Phase 3 ASPIRE study. In ENDEAVOR, the rates for cardiac and renal failure were higher in the Kyprolis arm versus the Velcade arm. There was an increase in the incidence of hypertension and dyspnea in the Kyprolis arm compared to Velcade and that observed in the ASPIRE study.

Full data will be submitted for presentation at the American Society of Clinical Oncology 2015 Annual Meet­ing.

"We are excited about the results with Kyprolis in the ENDEAVOR and ASPIRE studies and the potential positive impact for patients with relapsed multiple myeloma," said Robert A. Bradway, chairman and chief executive officer at Amgen.

"As new treatment options become available to patients with relapsed multiple myeloma, comparative trials, like ENDEAVOR, are becoming increasingly important to help physicians make informed decisions about the optimal care for patients," said Pablo J. Cagnoni, M.D., president, Onyx Pharmaceuticals, Inc. "Demonstrating superiority over Velcade in this head-to-head trial supports our goal of ensuring continued improvement of patient outcomes and potentially establishing Kyprolis as the backbone of therapy for patients with multiple myeloma."

The ENDEAVOR study is the first of two head-to-head studies for Kyprolis versus Velcade, an established proteasome inhibitor, currently approved to treat multiple myeloma.

About ENDEAVOR

The randomized ENDEAVOR (RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExa­methA­­sone Vs Bortezomib Plus Dexa­metha­sOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated Kyprolis in combination with low-dose dexa­meth­a­sone, versus Velcade with low-dose dexa­meth­a­sone in patients whose multiple myeloma has relapsed after at least one, but not more than three prior thera­peutic regimens. The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death.

Patients received Kyprolis as a 30 minute infusion along with low-dose dexa­meth­a­sone (20 mg). For Cycle 1 only, Kyprolis was administered 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 were kept at this dose for subsequent cycles on days 1, 2, 8, 9, 15, and 16 on a 28 day cycle. Patients who received Velcade (1.3 mg/m2) with low-dose dexa­meth­a­sone (20 mg) were administered Velcade subcutaneously or intravenously at the discretion of the investigator and in accordance with regulatory approval of Velcade. More than 75 percent of the patients in the control arm received Velcade subcutaneously. This study was conducted at 235 sites worldwide. For information about this trial, please visit http://www.clinicaltrials.gov under trial identification number NCT01568866.

Complete press release:

"Phase 3 Head-to-Head ENDEAVOR Study Demonstrates Superiority Of Kyprolis® (Carfilzomib) Over Velcade® (Bortezomib) In Patients With Relapsed Multiple Myeloma," March 1, 2015.

[coachhoke]

Re: Kyprolis vs. Velcade in relapsed myeloma - trial results

by coachhoke on Mon Mar 02, 2015 12:07 am

Please explain PFS in this trial:

1.  From time first relapse is discovered, until second relapse is discovered?
     a. And their definition of relapse?

2. Or, from the start of new treatment with Velcade or Kyprolis until second relapse?

3. Or what?

Thanks,
Coach Hoke

[Beacon Staff]

Re: Kyprolis vs. Velcade in relapsed myeloma - trial results

by Beacon Staff on Mon Mar 02, 2015 7:32 am

Hi Coach Hoke,

Thanks for your questions.

We won't know for certain the definition of PFS used in this trial until more data from the trial are published.

However, more than likely, the starting point for the calculation of PFS will be either the start of treatment with Velcade or Kyprolis, or the time at which the patient entered the trial.

Progression usually is measured based on changes in a patient's M-spike (paraprotein level). If the M-spike increases by more than 25 percent (but at least by 0.5 g/dL), and this change is confirmed by two consecutive M-spike measurements, then progression has occurred.

For further information and a link with detailed information, please see this previous forum discussion where we posted feedback in response to a similar question that you asked.

Note that "relapse" and "progression" are not exactly the same thing. This is mentioned by Beacon Medical Advisors Dr. Kaufman and Dr. Valent in this forum discussion on the topic of the definition of relapse.

[coachhoke]

Re: Kyprolis vs. Velcade in relapsed myeloma - trial results

by coachhoke on Mon Mar 02, 2015 9:34 am

Thank you for bearing with me, but I think how PFS is measured is very important. As you have pointed out, it seems that progression and relapse are used almost interchangeably, which needs to be clarified, and so I will try to be patient until further details are available.

Bottom line, however, is good news; Kyprolis seems to work even better than Velcade.

[DallasGG]

Re: Kyprolis vs. Velcade in relapsed myeloma - trial results

by DallasGG on Mon Mar 02, 2015 11:12 am

My question is ...

Could a patient take Velcade until it stops working, using up the benefit of that drug, and only then start taking Kyprolis and still get the full benefit from Kyprolis? Or does the multiple myeloma change so that it will not respond as well to Kyprolis after taking Velcade?

[Nancy Shamanna]

Re: Kyprolis vs. Velcade in relapsed myeloma - trial results

by Nancy Shamanna on Mon Mar 02, 2015 5:30 pm

Thanks for this information regarding the 'Endeavor' study. Results of Phase 3 trial data are what is needed for a drug company such as Onyx (owned by Amgen) to apply for approval to Health Canada. It seems that the trial data are quite positive for carflilzomib (Kyprolis), so probably they would apply to HC in the near future! When would the final results of the phase 3 trial be known? Is it at 2015 ASH that they would be released, do you think?

[cindylouise]

Re: Kyprolis vs. Velcade in relapsed myeloma - trial results

by cindylouise on Tue Mar 03, 2015 8:46 am

So it sounds like Kyprolis may not be the best choice, tho, if you have kidney and cardiac issues? That was my take, so someone please correct me if I'm wrong. I'm often wondering what my husband's options will be, should he relapse.

[Tracy J]

Re: Kyprolis vs. Velcade in relapsed myeloma - trial results

by Tracy J on Tue Mar 03, 2015 9:22 am

Anecdotally, I can say that Dr. Laubach at Dana Farber recommended Krypolis (carfilzomib) for me after I relapsed on Velcade (bortezomib). AND I'm responding to carfilzomib, with complete resolution of the active bone tumors.

[JimNY]

Re: Kyprolis vs. Velcade in relapsed myeloma - trial results

by JimNY on Tue Mar 03, 2015 10:20 am

Coachhoke,

The Amgen press release included in the first posting in the thread says that "The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death."

[coachhoke]

Re: Kyprolis vs. Velcade in relapsed myeloma - trial results

by coachhoke on Tue Mar 03, 2015 10:53 am

Thanks JimNY,

Now I understand when the clock started ticking, but not when it ended (other than death).
What I'm waiting to hear is their definition of disease progression. I'm still struggling with their difference between relapse and disease progression (are we just using M-spike as a gauge or do we need a CRAB feature?)

Coach Hoke