Most Read Articles
Prof Winnie Yeo, 13 Aug 2020
Despite the availability of antiemetics, a substantial proportion of patients receiving chemotherapy experience chemotherapy-induced nausea and vomiting (CINV), significantly impacting treatment compliance and quality of life (QoL). At the 24th Annual Scientific Symposium of the Hong Kong Cancer Institute, Professor Winnie Yeo of the Department of Clinical Oncology, Chinese University of Hong Kong, presented results of a local study showing superior efficacy of the fixed-dose netupitant/palonosetron (NEPA) combination regimen vs aprepitant-based regimen in controlling CINV in breast cancer patients receiving highly emetogenic anthracycline-cyclophosphamide (AC) chemotherapy.
Prof. Charlie Gourley, 30 Sep 2020

First-line poly(ADP-ribose)polymerase (PARP) inhibitor maintenance therapy significantly increases progression-free survival (PFS) in high-grade ovarian cancer patients. However, questions remain regarding the ability of PARP inhibitors to increase the cure rate, the types of patients most likely to benefit from them, and when it is best to employ them. In a virtual small-group meeting with experts in Hong Kong, Professor Charlie Gourley of the University of Edinburgh, Edinburgh, UK discussed the criteria for optimal patient selection and the positioning of PARP inhibitors in the patient journey.

Dr. Kathleen Moore, 30 Sep 2020
Most patients with advanced ovarian cancer (OC) relapse after standard cytoreductive surgery and platinum-based chemotherapy. At a webcast organized by the Hong Kong Society of Clinical Oncology, Dr Kathleen Moore of the University of Oklahoma in Norman, Oklahoma, US, discussed the results of the SOLO-1 trial, which demonstrated significant progression-free survival (PFS) benefits associated with maintenance therapy using the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitor, olaparib, in patients with newly diagnosed, advanced BRCA-mutated OC who had complete or partial response (CR/PR) to first-line platinum-based chemotherapy. 
05 Aug 2020
With ageing populations, many countries face increasing healthcare demands associated with the management of diseases and comorbidities common among the elderly, such as cancer, osteoarthritis and rheumatoid arthritis, and the pain associated with these conditions. In recent years, there has been growing evidence supporting the use of sustained-release (SR) oxycodone (OxyContin®, Mundipharma) as a pain management option for elderly patients, particularly those experiencing chronic cancer-related pain. This article summarizes the key points and evidence from two seminal papers – a consensus statement of an international expert panel on opioids and the management of chronic severe pain in the elderly as well as a multicentre, open-label randomized controlled trial investigating the efficacy and safety of SR oxycodone in cancer pain treatment. 

Role of ponatinib in management of CML and Ph+ ALL

Dr. Herman Sung-Yu Liu
Specialist in Haematology & Haematological Oncology
Private practice
Hong Kong
03 Aug 2020
Although first- and second-generation tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL), resistance or intolerance to these agents has limited their effectiveness, particularly in patients who harbour the BCR-ABLT315I mutation. In an interview with MIMS Oncology, Dr Herman Sung-Yu Liu, Specialist in Haematology & Haematological Oncology in private practice in Hong Kong, discussed the management of CML and Ph+ ALL using the third-generation TKI, ponatinib, the only agent in its class with activity against the T315I mutation. 

Efficacy of ponatinib in CML and Ph+ ALL

Ponatinib is a potent TKI that binds to native and mutant forms of BCR-ABL, including the BCR-ABLT315I mutant. It is indicated for patients with CML or Ph+ ALL who are resistant or intolerant to prior TKIs, or who have the T315I mutation. [Iclusig Hong Kong Prescribing Information, Jan 2019]

“The introduction of ponatinib has been a major breakthrough for TKI-refractory patients harbouring the T315I mutation,” noted Liu. “Transplantation was the only viable option for these patients. With ponatinib becoming available, these patients can now be spared from transplant-related morbidity and mortality.”

The pivotal phase II PACE trial demonstrated deep and durable molecular responses to ponatinib at a starting dose of 45 mg/day in 449 patients with CML or Ph+ ALL who were resistant or intolerant to dasatinib or nilotinib, or who had the T315I mutation. [N Engl J Med 2013;369:1783-1796; Blood 2018;132:393-404]

In a retrospective analysis of trials comparing ponatinib with earlier-generation TKIs, with all agents being used in combination with chemotherapy, complete molecular response (CMR) was achieved in 79 percent of patients on ponatinib vs 34 percent of patients on other TKIs. [Clin Lymphoma Myeloma Leuk 2018;18:257-265]

In the phase III EPIC trial, 307 newly diagnosed CML patients in chronic phase were randomized to receive ponatinib (45 mg/day) or imatinib (400 mg/day). The study was terminated prematurely due to safety concerns about vascular occlusive events associated with ponatinib in other trials. [Lancet Oncol 2016;17:612-621]

“Despite the short duration of median follow-up [5.1 months] and the small number of evaluable patients, preliminary results showed higher molecular response rates with ponatinib vs imatinib,” highlighted Liu. (Figure)

OTS-020_01

“Reaching major molecular response [MMR] is a major landmark in CML treatment as it represents a ‘safe haven’ where the probability of subsequent progression to accelerated or blast phase is very low. These results should translate to better progression-free survival or overall response,” commented Liu.

Managing CV toxicities of ponatinib

At a median follow-up of 12 months, 5 percent of patients in the PACE trial experienced myocardial ischaemic serious adverse events, but the majority of these patients had pre-existing cardiovascular (CV) disease or risk factors. [J Clin Oncol 2013;31(15 suppl):7048]

“Patients with CV risk factors, such as smoking, hyperlipidaemia, hypertension and diabetes, should be closely monitored during treatment,” cautioned Liu. “Ponatinib should be avoided in patients with a history of stroke, deep vein thrombosis or ischaemic heart disease. However, if these patients are T315I mutation-positive, I would consider commencing ponatinib at a lower dose of 15 mg/day or 30 mg/day, along with concomitant antiplatelet therapy as recommended by a cardiologist.”

“Ponatinib treatment has also been associated with deranged liver function, but this can be reversed with dose modification in most patients,” said Liu. [N Engl J Med 2012;367:2075-2088]

When to de-escalate ponatinib dose?

“In patients who achieved satisfactory disease control, de-escalation of ponatinib dose from 45 mg/day to 30 mg/day, or 15 mg/day with regular monitoring, can be considered. This should be implemented on a case-by-case basis as there are no guidelines to direct such decisions,” said Liu.

“In Hong Kong, the decision to de-escalate ponatinib dose is typically based on achievement of MMR rather than major cytogenetic response, because monitoring for MMR is less invasive than bone marrow cytogenetic testing,” he added.

OTS-020mo_02r

Summary

Ponatinib is currently the only approved TKI with clinical activity against the T315I mutation. Initiation of ponatinib therapy should be carefully guided by weighing the risks and benefits for each patient, particularly in those already at increased risk of vascular events. Monitoring and management of pre-existing CV comorbidities, as well as appropriate dose reductions or interruptions, are important for reducing risk and optimizing treatment outcomes.

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Most Read Articles
Prof Winnie Yeo, 13 Aug 2020
Despite the availability of antiemetics, a substantial proportion of patients receiving chemotherapy experience chemotherapy-induced nausea and vomiting (CINV), significantly impacting treatment compliance and quality of life (QoL). At the 24th Annual Scientific Symposium of the Hong Kong Cancer Institute, Professor Winnie Yeo of the Department of Clinical Oncology, Chinese University of Hong Kong, presented results of a local study showing superior efficacy of the fixed-dose netupitant/palonosetron (NEPA) combination regimen vs aprepitant-based regimen in controlling CINV in breast cancer patients receiving highly emetogenic anthracycline-cyclophosphamide (AC) chemotherapy.
Prof. Charlie Gourley, 30 Sep 2020

First-line poly(ADP-ribose)polymerase (PARP) inhibitor maintenance therapy significantly increases progression-free survival (PFS) in high-grade ovarian cancer patients. However, questions remain regarding the ability of PARP inhibitors to increase the cure rate, the types of patients most likely to benefit from them, and when it is best to employ them. In a virtual small-group meeting with experts in Hong Kong, Professor Charlie Gourley of the University of Edinburgh, Edinburgh, UK discussed the criteria for optimal patient selection and the positioning of PARP inhibitors in the patient journey.

Dr. Kathleen Moore, 30 Sep 2020
Most patients with advanced ovarian cancer (OC) relapse after standard cytoreductive surgery and platinum-based chemotherapy. At a webcast organized by the Hong Kong Society of Clinical Oncology, Dr Kathleen Moore of the University of Oklahoma in Norman, Oklahoma, US, discussed the results of the SOLO-1 trial, which demonstrated significant progression-free survival (PFS) benefits associated with maintenance therapy using the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitor, olaparib, in patients with newly diagnosed, advanced BRCA-mutated OC who had complete or partial response (CR/PR) to first-line platinum-based chemotherapy. 
05 Aug 2020
With ageing populations, many countries face increasing healthcare demands associated with the management of diseases and comorbidities common among the elderly, such as cancer, osteoarthritis and rheumatoid arthritis, and the pain associated with these conditions. In recent years, there has been growing evidence supporting the use of sustained-release (SR) oxycodone (OxyContin®, Mundipharma) as a pain management option for elderly patients, particularly those experiencing chronic cancer-related pain. This article summarizes the key points and evidence from two seminal papers – a consensus statement of an international expert panel on opioids and the management of chronic severe pain in the elderly as well as a multicentre, open-label randomized controlled trial investigating the efficacy and safety of SR oxycodone in cancer pain treatment.