Haematology+Oncology_News

NEWS 5

Vol. 9 • No. 1 • 2016 • H aematology & O ncology N ews

EADV: Vismodegib treatment breaks don’t hurt efficacy

and partial response rates were 34% and 33%, respectively, in patients with locally advanced BCC, and 7% and 31% in those with meta- static disease (Lancet Oncol 2015 Jun;16[6]:729–36). Dr Hansson presented new data on efficacy outcomes broken down ac- cording to treatment breaks, as well as quality of life results, at the annual congress of the European Academy of Dermatology and Venereology. Twenty-six percent of patients had one or more treatment breaks. Seventy-six patients had one, 41 had two, and 14 had three or more. The median duration of the breaks was 22 days. The two most frequent reasons for treatment breaks were intolerable adverse events in 53% of cases, and lesser adverse events in 23%. Close to 100% of STEVIE par- ticipants had treatment-emergent adverse events. The most common were muscle spasms, alopecia, al- tered sense of smell, and weight loss. Although the number of pa- tients with treatment breaks was relatively small, the response rates were higher in patients with more treatment breaks. So was median treatment duration as well as the median number of capsules taken. Median progression-free survival was 19.8 months in patients with no treatment breaks, was 19.0 months

BY BRUCE JANCIN Frontline Medical News

BCC, with median improvements of 14.3 points after two cycles and 23.8 points after seven cycles and at the 12-month mark. Clinically meaning- ful improvement in symptom scores on the Skindex-16 were noted in pa- tients aged 65 and older, in women, and in those with BCCs in locations other than the head or neck. However, no clinically meaningful improvement in the domain of function was seen at any time in patients with locally advanced BCC. Patients with metastatic BCC didn’t show significant improvement in any of the three quality of life domains at any time point, added Dr Hansson. The STEVIE trial is sponsored by F. Hoffmann–La Roche/Genentech. Dr Hansson reported receiving re- search grants from and serving as a consultant to Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis, and Roche. We have to remember that although intriguing, these are tentative results from an exploratory analysis of subgroups in an ongoing study and should be interpreted with caution.

Impact of vismodegib treatment breaks

At the EADV congress 2015, Copenhagen T reatment breaks due to adverse events in patients taking vismo- degib for advanced basal cell carcinoma do not appear to com- promise the oral hedgehog pathway inhibitor’s efficacy; in fact, they might even enhance it, according to a prespecified interim analysis of the STEVIE trial. STEVIE is an ongoing phase II, long-term, open-label international study designed primarily to assess the safety of vismodegib in a situa- tion similar to routine clinical prac- tice. Efficacy and impact on quality of life are secondary endpoints. Al- though STEVIE has enrolled 1227 patients, a prespecified interim analysis was conducted in the first 499 followed for at least 12 months, of whom 468 had locally advanced basal cell carcinoma (BCC) and 31 had metastatic BCC, explained Dr Johan Hansson, an oncolo- gist at the Karolinska Institute in Stockholm. The drug was dosed at 150 mg once daily continuously in 28-day cycles until disease progression, intolerable toxicity, or study with- drawal. Safety follow-up was con- ducted at 1, 3, 5, 9, and 12 months. In an earlier report, the complete

Number of treatment breaks

None

One

Two

Three or more

Median treatment duration, days

223.5

289

399

454

Median dose intensity

97% 89% 86% 81%

Median number of capsules taken

215

256

354

380

Occurrence of grade 3 or higher TEAEs*

39% 45% 66% 79%

Grade 5 events

5% 4%

0

7%

Complete response

30% 33% 51% 39%

Partial response

31% 32% 44% 46%

Stable disease

28% 32% 5% 15%

*treatment-emergent adverse event Note: The interim analysis included the first 499 patients followed for at least 12 months. Source: Dr Hansson

deliberate intermittent dosing of vismodegib. Quality of life was assessed using the Skindex-16 questionnaire at baseline, again after two and seven 28-day cycles of vismodegib, and at 12 months. Three domains were examined: emotion, function, and symptoms. A clinically meaningful improve- ment – defined as a 10-point or greater reduction from baseline – was seen in the emotion domain at all time points in patients with locally advanced

in those with one, and hasn’t yet been reached in patients with two or more breaks. In interpreting these findings, Dr Hansson said, “We have to re- member that although intriguing, these are tentative results from an exploratory analysis of subgroups in an ongoing study and should be interpreted with caution.” The oncologist added, however, based upon these promising results he and his coinvestigators plan to look further into the concept of

RETHINK WHAT'S POSSIBLE...

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SEE APPROVED PRODUCT INFORMATION BEFORE PRESCRIBING. APPROVED PRODUCT INFORMATION AVAILABLE FROM HTTPS://WWW.EBS.TGA.GOV.AU/EBS/PICMI/PICMIREPOSITORY.NSF/PDF? OPENAGENT&ID=CP-2015-PI-01225-1 Minimum Product Information ZYDELIG ® (idelalisib) 100 mg and 150 mg Tablets. INDICATIONS: with rituximab for CLL/SLL where chemo-immunotherapy is unsuitable, either: upon relapse after at least one prior therapy, or first-line with 17p deletion or TP53 mutation. Monotherapy of refractory follicular lymphoma after at least two prior systemic therapies. DOSAGE AND ADMINISTRATION: 150 mg twice daily. Dose modification may be required. CONTRAINDICATIONS: hypersensitivity. PRECAUTIONS: Hepatotoxicity: monitoring required. Hepatitis Infection and Reactivation: prior screen for HBV and HCV. Diarrhoea/Colitis: assessment of hydration and dose interruption shouldbeconsidered inseverecases. Pneumonitis: Dose interruptionshouldbeconsideredwithanyseverityofsymptomaticpneumonitis. Immunisation: Vaccinationprior to treatmentofpatientsatsubstantialriskofan infection. Neutropenia, Anaemia, Lymphopenia and Thrombocytopenia. Severe Cutaneous Reactions: life-threatening (Grade ≥ 3) cutaneous reactions. Fatal cases of SJS-TEN have occurred when patients were treated with Zydelig when administered concomitantly with other medications associated with SJS-TEN. Treatment should be interrupted immediately if SJS or TEN is suspected and permanently discontinued where there is a case of severe cutaneous reaction. Intestinal Perforation: discontinue permanently. Progressive Multifocal Leukoencephalopathy (PML): diagnosis should be considered with new onset of, or changes in pre-existing neurologic signs and symptoms. Transient Lymphocytosis. Infections: patients with signs of infection should be promptly treated. Effects on Fertility: highly-effective contraception during and 1 month after. Pregnancy (Cat. D). Lactation. Children (<18 years). INTERACTIONS WITH OTHER MEDICINES: Effects of other drugs on Zydelig: CYP3A Inducers (rifampin, phenytoin, St. John’s Wort, or carbamazepine). CYP3A Inhibitors (ketoconazole). Effects of Zydelig on other drugs: CYP3A Substrates (alfentanil, cyclosporine, sirolimus, tacrolimus, cisapride, pimozide, fentanyl, quinidine, ergotamine, dihydroergotamine, midazolam, certain antiarrhythmics, calcium channel blockers, benzodiazepines, HMG-CoA reductase inhibitors, phosphodiesterase-5 (PDE5) inhibitors,

and warfarin), refer to full PI. ADVERSE EFFECTS: Neutropenia, Pneumonitis, Diarrhoea/Colitis, Transaminases increased, Rash, Pyrexia. This is not the full Product Information. Please review the full Product Information before prescribing. Product Information is available on request from Gilead Sciences Pty Ltd. Date of preparation 16 December 2015. References: 1. Furman RR et al. N Engl J Med 2014;370:997–1007. 2. Sharman JP SE et al. Second Interim Analysis of a Phase 3 Study of Idelalisib (ZYDELIG ) Plus Rituximab (R) for Relapsed Chronic Lymphocytic Leukemia (CLL): Efficacy Analysis in Patient Subpopulations with Del(17p) and Other Adverse Prognostic Factors. The American Society of Hematology (ASH) 56th Annual Meeting, 6–9 December 2014, San Francisco, CA, USA: Abstract 330. 3. Coutre SE et al. Second interim analysis of a phase 3 study evaluating idelalisib and rituximab for relapsed CLL. J Clin Oncol 2014;32(Suppl): Abstract 7012. 4. Gopal AK et al. N Engl J Med 2014;370:1008–18 4. Salles G et al. Idelalisib efficacy and safety in follicular lymphoma patients from a phase 2 study. J Clin Oncol 2015;33(Suppl): Abstract 8529. 6. Zydelig Product Information, 16 December 2015.

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