Practice Update | Onology

ASCO 2017 19

Dr Wen: I think initially a lot of the trials were done in recurrent disease so this follows radiation therapy and temozolomide, both of which can produce a fairly profound lym- phopenia. And then the tumors are often bulky when patients are on steroids. So in that setting, trying to stimulate the immune system is probably a real challenge. I think many of the newer studies are in first-line setting in patients who’ve had a gross total resection. There isn’t a lot of residual disease that can produce immu- nosuppressive factors and where the patient’s immune system is more robust because they’ve just started their treat- ment with radiation or temozolomide. And in some of these patients and those who are MGMT-unmethylated, which temozolo- mide is not particularly useful, there’s been a trend to drop the temozolomide so these patients would get just the radiation and whatever immunotherapeutic agent is being planned with the hopes that by avoiding the temozolomide, the immune suppression will be avoided also. Those studies are ongoing. Dr Caudle: Let’s switch gears just a little bit. Can you elaborate on the recent study that was evaluating the use of a personalized

the randomized phase 3 study of nivolumab versus bevacizumab in recurrent glioblas- toma. That was presented at the World Federation of Neuro-Oncology Societies just a few months ago, and unfortunately that trial was negative. There was no differ- ence in outcome between nivolumab and bevacizumab in recurrent glioblastoma. But what they did in this trial was they looked at those patients who appear to be progress- ing and had surgery to see if they could look at the pathology to differentiate those patients who are truly progressing and those patients who may have what’s called pseudo-progression or an inflammatory response. They actually didn’t see a lot of inflammation in these tumors and the patho- logic analysis did not really predict outcome. So that’s an area that we still need to do a lot of work on separating pseudo-progres- sion from true tumor progression. Dr Caudle: You mentioned briefly the con- cept of timing, especially for immune therapies, and I want to talk a little bit about that. When during therapy do you think is the optimal timing for the integration of immune therapies, particularly given the immune suppression inherent in standard adjuvant therapy?

peptide vaccine in patients with refractory GBMs and how this new class of agents can potentially move up to the upfront setting? Dr Wen: Yes. So they used peptide vaccines and tried to match it to the patient’s geno- type. In fact, there are a number of these studies now ongoing in the first-line set- ting both in Europe and then in the US. At Dana-Farber, my colleague David Reardon is running one of these trials for the vaccine called NeoVax where patients get whole-ex- ome sequencing and then, depending on the mutations, a personalized vaccine is made for that patient. It’s administered to the patient after radiation and temozolomide with the plan to add a PD-1 antibody to that regimen. I think that these approaches are really exciting and there’s more and more of these being developed.

Jennifer Caudle DO is Assistant Professor at Rowan University School of Osteopathic Medicine in New Jersey.

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FROM 1 ST FEBRUARY 2017

PBS Information: Lynparza. Authority Required. For maintenance treatment of germline BRCA mutated platinum-sensitive relapsed high-grade serous ovarian, fallopian tube or primary peritoneal cancer for patients who have responded to prior platinum based chemotherapy. Refer to PBS schedule for full authority information.

Explanatory note: Patients who are found to have a germline BRCA1 or BRCA2 mutation should be referred for post-test genetic counselling, as there may be implications for other family members. Appropriate genetic counselling should be provided to the patient either by the specialist treating practitioner, a genetic counselling service or a clinical geneticist on referral.

MBS item 73295: Detection of germline BRCA1 or BRCA2 gene mutations, in a patient with platinum-sensitive relapsed ovarian, fallopian tube or primary peritoneal cancer with high grade serous features or a high grade serous component, and who has responded to subsequent platinum-based chemotherapy, requested by a specialist or consultant physician, to determine whether the eligibility criteria for olaparib under the Pharmaceutical Benefits Scheme ( PBS ) are fulfilled.

BEFORE PRESCRIBING, PLEASE REVIEW FULL PRODUCT INFORMATION AVAILABLE ON REQUEST FROM ASTRAZENECA ON 1800 805 342 OR www.astrazeneca.com.au/PI LYNPARZA ® ( olaparib ) Minimum Product Information: INDICATIONS: Monotherapy for the maintenance treatment of patients with platinum - sensitive relapsed BRCA - mutated ( germline or somatic ) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response ( complete response or partial response ) after platinum - based chemotherapy. Prior treatment must have included at least 2 courses of platinum - based regimens. CONTRAINDICATIONS: Hypersensitivity to the active substance ( olaparib ) or to any of the excipients. PRECAUTIONS: Haematological toxicity is common in patients treated with olaparib and usually mild - moderate. Patients should not start treatment with LYNPARZA until they have recovered from haematological toxicity caused by previous anti - cancer therapy. A baseline complete blood count followed by monthly monitoring is recommended for the first 12 months of treatment and periodically after this. Myelodysplastic syndrome/Acute Myeloid Leukaemia ( MDS/AML ) have been reported in a small number of patients ( <1% ) and the majority of reports have been fatal. Pneumonitis has been reported in a small number of patients receiving olaparib, and some reports have been fatal. Use in pregnancy: Category D. LYNPARZA may cause foetal harm when administered to a pregnant woman. Women of child bearing potential must use effective contraception during treatment and for 1 month after receiving the last dose. Use during lactation: Breast feeding should be avoided in women receiving LYNPARZA and for 1 month after the last dose. Use in Men: Not indicated Children or adolescents: Not indicated. Interactions with other medicines. INTERACTIONS: LYNPARZA co administration with strong CYP3A inducers or inhibitors should be avoided. Addition of LYNPARZA and cytotoxic agents has been shown to potentiate and prolong myelosuppressive side effects. ADVERSE REACTIONS : Very common ( ≥10% ) : decreased appetite, headache, dysgeusia, dizziness, nausea, vomiting, diarrhoea, dyspepsia, fatigue, anaemia, neutropenia, lymphopenia, mean corpuscular volume elevation, increased creatinine; Common ( ≥1% to <10% ) : stomatitis, upper abdominal pain, thromboyctopenia; for other listed adverse reactions, see full PI. DOSAGE AND ADMINISTRATION: 400 mg ( eight 50 mg capsules ) taken twice daily, equivalent to a total daily dose of 800 mg. LYNPARZA should be taken on an empty stomach and patients should refrain from eating for 2 hours. Date of first inclusion in the ARTG: 7th January 2016. References 1. Lynparza Approved Product Information 10 October 2016. 2. PBS Website http://www.pbs.gov.au/pbs/home [Accessed 1 February, 2017]. Lynparza TM is a trademark of the AstraZeneca group of companies. AstraZeneca Pty. Ltd. ABN 54 009 682 311. 66 Talavera Road, Macquarie Park, NSW 2113. AstraZeneca Medical Information: 1800 805 342. www.astrazeneca.com.au. AU-2176, WL294703, February 2017.

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