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14 Sep 2020
Osteoarthritis (OA) is the most common condition affecting the joints. Dr Lee Eu Jin, an Orthopaedic Surgeon from Liberty Orthopaedic Clinic at Mount Elizabeth Medical Centre, Singapore, shares his insights with Pearl Toh on how to manage OA in the primary care setting.


27 Sep 2019
Quadrivalent influenza vaccine (split virion, inactivated) 0.5 mL inj
Stephen Padilla, 27 May 2020
Use of oral fluconazole in the first trimester does not lead to oral clefts or conotruncal malformations but is associated with musculoskeletal malformations, a study has shown.
Stephen Padilla, 17 Dec 2019
The use of aspirin for primary prevention in patients without known cardiovascular diseases (CVDs) significantly reduces the risk of myocardial infarction (MI) but increases that of major bleeding and haemorrhagic stroke, according to a meta-analysis.

Ivosidenib a ray of hope for rare biliary tract cancer?

Audrey Abella
22 Jul 2020

Ivosidenib, a potent targeted inhibitor of mutated IDH1*, provided benefit for patients with IDH1-mutant, chemotherapy(CT)-refractory cholangiocarcinoma (CC), the ClarIDHy study has shown.

IDH1 mutations occur in ~13 percent of patients with intrahepatic CC, a relatively uncommon cancer with poor clinical outcomes. [J Gastrointest Oncol 2019;10:751-765; Oncologist 2012;17:72-79] Surgery is the only curative option for localized CC, while CT is the main alternative for unresectable/metastatic disease. However, recurrence rates are high, noted the researchers.

“[The] global incidence of [CC] is increasing … Although CC-associated genetic alterations are now better defined, there are still no approved targeted therapies, [hence the growing unmet need],” they said. “[Our findings] establish the efficacy and safety of ivosidenib in [this setting, suggesting] the clinical benefit of targeting IDH1 mutations.”

A total of 185 patients were randomized 2:1 to receive oral ivosidenib 500 mg or placebo QD in continuous 28-day cycles. [Lancet Oncol 2020;21:796-807]

After a median follow up of 6.9 months, progression-free survival (PFS) was markedly improved with ivosidenib vs placebo (median, 2.7 vs 1.4 months; hazard ratio [HR], 0.37; one-sided p<0.0001). PFS rates with ivosidenib were 32 percent and 22 percent at 6 and 12 months, respectively, while none from the placebo arm were progression-free for ≥6 months.

“Although the absolute improvement in median PFS seems modest, the statistical strength of the HR reflects a high reduction in risk of progression, along with a substantial improvement in the proportion of patients progression-free at 6 and 12 months,” explained the researchers.

“The benefit is independent of [the] number of previous therapies and is consistent across most subgroups. This [PFS] improvement is important in the context of a favourable safety and tolerability profile in the CT-refractory setting,” they continued.

Despite more ivosidenib vs placebo recipients experiencing serious adverse events (AEs; 30 percent vs 22 percent), ivosidenib was generally well-tolerated. The most common treatment-emergent AEs (TEAEs) were low-grade nausea, diarrhoea, and fatigue. No treatment-related deaths were reported. There were low TEAE (6 percent) and treatment-related AE rates (2 percent) leading to ivosidenib withdrawal. These highlight the encouraging safety of ivosidenib, noted the researchers.

The EORTC QLQ-C30** physical functioning subscale decline from baseline at cycle 2 day 1 was markedly less with ivosidenib vs placebo (least squares mean, −3.4 vs –13.1; p=0.0059). “Despite small post-baseline sample sizes, [this implies] that patients receiving placebo had a significantly greater decline in physical functioning than did patients receiving ivosidenib,” they stressed.

 

Tumour mutation profiling

Ivosidenib is approved for newly diagnosed, CT-ineligible, and relapsed/refractory AML***. [N Engl J Med 2018;378:2386-2398; ACS Med Chem Lett 2018;9:300-305] The current findings reinforce the results of a phase I trial reflecting similar findings in a similar patient group. [Lancet Gastroenterol Hepatol 2019;4:711-720]

Although specific to a small subset, the study underscores the potential benefit of targeting a molecularly defined subgroup of CC, noted the researchers. As such, tumour mutation profiling could be a new standard of care in the management of this rare heterogeneous c­ancer, they said.

 

OS benefit?

Median overall survival (OS) was longer with ivosidenib vs placebo; however, the difference was not significant (10.8 vs 9.7 months; HR, 0.69; p=0.06). This, as per the researchers, could be due in part to the high placebo-ivosidenib crossover rate (57 percent) and the immature OS data.

Nonetheless, the RPSFT#-adjusted median OS of 6 months for placebo reflected a significant OS improvement (HR, 0.46; p=0.0008). As such, the OS finding may be deemed favourable, they said.

The current findings alongside mature OS data shall be used to support the application for regulatory approval of ivosidenib, they added.

 

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Most Read Articles
14 Sep 2020
Osteoarthritis (OA) is the most common condition affecting the joints. Dr Lee Eu Jin, an Orthopaedic Surgeon from Liberty Orthopaedic Clinic at Mount Elizabeth Medical Centre, Singapore, shares his insights with Pearl Toh on how to manage OA in the primary care setting.


27 Sep 2019
Quadrivalent influenza vaccine (split virion, inactivated) 0.5 mL inj
Stephen Padilla, 27 May 2020
Use of oral fluconazole in the first trimester does not lead to oral clefts or conotruncal malformations but is associated with musculoskeletal malformations, a study has shown.
Stephen Padilla, 17 Dec 2019
The use of aspirin for primary prevention in patients without known cardiovascular diseases (CVDs) significantly reduces the risk of myocardial infarction (MI) but increases that of major bleeding and haemorrhagic stroke, according to a meta-analysis.