Practice Update: Haematology & Oncology

ASCO 2016

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After radical prostatectomy, menwant to know if they are cured or require further treatment. Physicians treating prostate cancer want to use genomic information, but only if this information changes what theywould do or recommend. >14

Patients with anaplastic glioma with codeletion of chromosome arms 1 p and 19q tend to respond better to chemotherapy and live longer. >15

Abemaciclibmay be able to be used as a single agent in this particular setting, and we await the results from the combination studies in the next year or two to see if we have another agent that can be combined with anti-endocrine therapy. >19

Undetermined: Whether lung

cancer patients with autoimmune disease are candidates for immunotherapy G iven the promise of cancer immunotherapy and the wide prevalence of autoimmune diagnoses among lung cancer patients, research to determine whether these patients are candidates for such treatment is warranted. This conclusion, based on results of a database quantifi- cation of lung cancer patients with autoimmune conditions was presented at the 2016 ASCO annual meeting. Dr David E. Gerber, of the University of Texas South- western Medical Center, Dallas, explained that immune checkpoint inhibitors have emerged as a highly promising treatment option for advanced lung cancer. Pre-existing autoimmune conditions, with some exceptions, are con- sidered contraindications to these treatments. To estimate the potential effect of this exclusion policy, Dr Gerber and colleagues set out to determine the preva- lence of autoimmune conditions among patients with lung cancer. Using linked the American Surveillance Epidemiology and End Results (SEER)–Medicare data 1991–2010, the investigators identified lung cancer patients with Interna- tional Classification of Diseases-9 codes for seven systemic and 36 organ-specific autoimmune conditions. Autoimmune diagnoses g considered acceptable for immunotherapy (for example, type 1 diabetes, vitiligo, hypothyroidism) were not included. Characteristics of patients with and without autoimmune diagnoses were compared using Chi-square testing. Survival was compared using unadjusted Kaplan- Meier and multivariable adjusted Cox proportional hazard models. Among 210,509 patients with lung cancer, 51,732 (24.6%) also had been diagnosed with an autoimmune condition. The most common autoimmune conditions were rheumatoid arthritis (9%), psoriasis (4.4%), polymyalgia rheumatica (2.6%), Addison’s disease (1.9%), giant cell arteritis (1.4%) and ulcerative colitis (1.3%). Autoimmune diagnoses were more likely to occur in older, female lung cancer patients and those who presented with earlier-stage disease (all P <  0.001). In multivariable Cox models, patients with autoimmune diagnoses experienced improved lung cancer-specific (hazard ratio 0.86; 95% confidence interval 0.85–0.87; P <  0.001) and all-cause (hazard ratio 0.88; 95% confi- dence interval 0.87–0.89, P < 0.001) survival. Dr Gerber concluded that autoimmune diagnoses occur among a substantial proportion of patients with lung cancer. Patients with autoimmune diagnoses (vs those without) are more likely to be older, female, have earlier-stage disease, and have improved clinical outcomes. Given the promise of cancer immunotherapy and prevalence of autoimmune diagnoses among lung cancer patients, additional research to determine whether these patients are candidates for such treatment is warranted.

Adjuvant temozolomide improves outcomes in anaplastic glioma without the 1p/19q codeletion Patients with anaplastic glioma without the 1p/19q codeletion have been shown to benefit from adjuvant chemotherapy, according to early results from a European phase 3 trial. E stimated 5-year survival rates were 56% with radiation therapy and adjuvant temozolomide vs 44% without ad- juvant temozolomide. Addition of adjuvant temozolomide also delayed disease progression by more than 2 years.

with or without concurrent temozolomide experienced slower disease progression than those treated without adjuvant therapy. The median time to disease progression was more than double in in the adjuvant temozolomide group (42.8 vs 19 months). Median overall survival has not been reached in patients treated with adjuvant temozolomide. Long-term survival esti- mates also support the use of adjuvant temozolomide. Fifty-six percent of patients were alive at 5 years with adjuvant temozolo- mide vs 44% with radiation therapy alone or with temozolomide given during radiation therapy. Results of temozolomide treat- ment given only during radiation therapy are not yet available and final data are expected in 2020. Temozolomide, an oral drug, is generally well tolerated. The most common toxicities in the temozolomide study arms were mainly hematologic, with severe toxicity in 5 to 10% of patients. Dr van den Bent concluded, “Until this study, doctors had no evidence to support the use of adjuvant temozolomide in patients with grade 3 anaplastic glioma. The findings should expand treatment choices and change the way we treat patients with this rare form of brain cancer.” Future research will focus on identifying patients most likely to benefit from adjuvant temozolomide. The researchers plan to assess or reexamine MGMT promoter methylation and IDH mutation, additional genetic abnormalities known to affect prognosis in anaplastic glioma.

Dr Martin J. van den Bent of Erasmus MC Cancer Center, Rotterdam, The Netherlands, explained that anaplastic glio- mas are uncommon, accounting for about 2% of primary brain cancers and highly aggressive tumours. They often occur in young adults. Median age at diagnosis is 35–50 years. Grade 3 anaplastic gliomas can grow quickly and progress to glioblas- toma within a few years of diagnosis. Patients with anaplastic glioma with codeletion of chromo- some arms 1 p and 19q tend to respond better to chemotherapy and live longer. The Concurrent and Adjuvant Temozolomide Chemotherapy in Non-1p/19q Deleted Anaplastic Glioma (CATNON) trial was limited to patients who lack 1p/19q codeletion. A separate trial focuses on patients with the marker. Researchers randomly assigned 748 patients from 118 institu- tions in Europe, NorthAmerica, andAustralia to four treatment groups: • Radiation therapy alone • Temozolomide during radiation therapy • Temozolomide during and after radiation therapy • Temozolomide after radiation therapy Patients who received temozolomide after radiation therapy

VOL. 1 • No. 2 • 2016