Probability of Perifosine success in Multiple Myeloma.
If anyone wants to understand the probability of Perifosine working in the current population of bortezamib relapsed patients, then you should read this recent paper. This is the most contemporary study of how such patients behave, which can be compared to the Perifosine-Bortezamib Phase II data.
Br J Haematol. 2013 Mar;160(5):649-59. doi: 10.1111/bjh.12198. Epub 2013 Jan 7.
A prospective, international phase 2 study of bortezomib retreatment in patients with relapsed multiple myeloma.
Petrucci MT, Giraldo P, Corradini P, Teixeira A, Dimopoulos MA, Blau IW, Drach J, Angermund R, Allietta N, Broer E, Mitchell V, Bladé J.
Department of Cellular Biotechnology and Haematology, Sapienza University of Rome, Rome, Italy.
According to the Phase II paper by Richardson et al., 45/73 (62%) patient received dex. with the bortezamib/perifosine. Whereas, in the Petrucci paper, 92/126 (73%). So actually, overall the Petrucci study received more dex.
There are some important things to point out.
In the Petrucci study, the progression free survival for the 40% of patients that were responders (CR and PR) was 8.4 months. Whereas, for the relapsed patients in the perifosine study it was 8.8 months for all of the patients, not just the best responding 40% - that is an important difference.
The important thing to remember is that the Petrucci study patients were much healthier. By definition of that study, the patients had only received one treatment phase with Bortezamib. Whereas in the perifosine phase II, many had received 2 prior treatments with Bortezamib (although the median was still 1).
In the Petrucci study, patients had received a median number of 2 prior therapies, whereas for the relapsed patients in the perifosine phase II, they had received a median of 4 prior therapies. The Petrucci study also nicely showed that the response rate for patients with = 4 or more therapies was 64% of that for patients with 2 prior therapies. So again, the perifosine study is doing much better than expected.
In the perifosine phase study 3/73 (4%) had a complete response, and 53 of these were bortezamib refractory (2/20 of the relapsed patients had a complete response). Whereas, out of the 126 in the relapsed (and healthier) Petrucci study patients only 1 (
Right. The previous Phase II study gave us information on how the patients responded to Bortezamib/dexamethasone/Perifosine. But this study was just a single arm. What was missing was a good understanding of how patients would of responded if they were just given Bortezamib and Dexamethasone. This paper now gives us that missing information.