New optimism for patients New optimism for patients with cancer with cancer As cancer therapy evolves, new As cancer therapy evolves, new regimens and novel agents that regimens and novel agents that target specific cellular processes target specific cellular processes allow a more optimistic prognosis allow a more optimistic prognosis for many patients for many patients Bortezomib and tipifarnib are two Bortezomib and tipifarnib are two new targeted treatments for new targeted treatments for hematologic malignancies hematologic malignancies
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New optimism for patients with cancer n As cancer therapy evolves, new regimens and novel agents that target specific cellular processes allow a more optimistic.
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New optimism for patients with New optimism for patients with cancer cancer
As cancer therapy evolves, new regimens As cancer therapy evolves, new regimens and novel agents that target specific and novel agents that target specific cellular processes allow a more optimistic cellular processes allow a more optimistic prognosis for many patientsprognosis for many patients
Bortezomib and tipifarnib are two new Bortezomib and tipifarnib are two new targeted treatments for hematologic targeted treatments for hematologic malignancies malignancies
BortezomibBortezomib
A proteasome inhibitorA proteasome inhibitor
Has shown good efficacy as a single agent and in Has shown good efficacy as a single agent and in combination in patientscombination in patients
– with relapsed multiple myelomawith relapsed multiple myeloma
– as initial treatment, including prior to autologous as initial treatment, including prior to autologous stem cell transplantationstem cell transplantation
Has been studied as monotherapy and in combination Has been studied as monotherapy and in combination with standard treatments, such as dexamethasone, with standard treatments, such as dexamethasone, chemotherapy, and with newer agents such as the IMiDs, chemotherapy, and with newer agents such as the IMiDs, thalidomide and lenalidomide thalidomide and lenalidomide
Is well-tolerated, including in combination Is well-tolerated, including in combination
Diagnosis to death
Relapsed disease• Transient response
to therapy
Relapsed and refractory• Resistant to all therapy• Universally fatal
Survival (years)
1–2 years
3–4 years
0 51 2 3 4
6–9 months
Clinical course of multiple myelomaClinical course of multiple myeloma
Single-agent bortezomib active in Single-agent bortezomib active in newly diagnosed MMnewly diagnosed MM
Well tolerated: safety profile similar to previous studies Well tolerated: safety profile similar to previous studies – Neuropathy frequently prevalent at baselineNeuropathy frequently prevalent at baseline
*Stem cells successfully harvested from 13 patients: 12 received transplants*Stem cells successfully harvested from 13 patients: 12 received transplants
Richardson Richardson et alet al..
RR (CR+PR), n=28RR (CR+PR), n=28 45%45% (67% including MR) (67% including MR)
85%85% (after addition of Dex), (after addition of Dex), 20% CR+nCR 20% CR+nCR
Richardson et al. Blood 2004;104:100a (abstract 336)Jagannath et al. Haematologica 2005;90(Suppl 1):148 (abstract P0.725)
Bortezomib + dexamethasone Bortezomib + dexamethasone in newly in newly diagnosed MMdiagnosed MM Data available for 46/52 patientsData available for 46/52 patients
Stem cell collection adequate for all patients (median CD34+ cells Stem cell collection adequate for all patients (median CD34+ cells 6.7 x 106.7 x 1066/kg; range 2–33); median 2 collections required (range 1–4) /kg; range 2–33); median 2 collections required (range 1–4)
A specific inhibitor of farnesyltransferaseA specific inhibitor of farnesyltransferase
Clinical trials in patients with high-risk Clinical trials in patients with high-risk acute leukemias and myelodysplastic acute leukemias and myelodysplastic syndromes have demonstrated good syndromes have demonstrated good efficacy with tipifarnib, even in patients efficacy with tipifarnib, even in patients with poor prognosis and elderly, poor-risk with poor prognosis and elderly, poor-risk patients patients
Oral formulationOral formulation Potent and selective inhibitor of farnesylationPotent and selective inhibitor of farnesylation
– Key enzyme involved in multiple tumor-promoting pathwaysKey enzyme involved in multiple tumor-promoting pathways
– Essential for the functioning of signal transduction cascades Essential for the functioning of signal transduction cascades associated with cell proliferationassociated with cell proliferation
Potent inhibitor of malignant cell line proliferationPotent inhibitor of malignant cell line proliferation
NH2
Cl
N
Cl
ON N
FarnesyltransferaseFarnesyltransferase
Key enzyme in many pathwaysKey enzyme in many pathways
Phase II trial of tipifarnib: efficacyPhase II trial of tipifarnib: efficacy
Harousseau et al. Presented at ASH 2003
Targeted therapyTargeted therapy
Is among the most exciting new development in cancer treatment
Specifically attacks the malignancy for improved efficacy and overall safety
Underscores an important shift in the treatment paradigm for multiple myeloma and other hematologic malignancies – a shift from empirical chemotherapeutic regimens with significant side effects towards rational, targeted, effective therapies with improved tolerability