PracticeUpdate: Haematology & Oncology

CONFERENCE COVERAGE

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If you’re going to not use a CDK4/6 inhibitor, then perhaps you want to start with fulvestrant. But if you are, the current data supports using letrozole and perhaps the combination, so I think we’re working it out. >9

If you don’t look at the subset analysis, you could make an argument that there is still room to treat low volume patients, but I think you’d select them very carefully to make sure that the benefit, which might be much smaller, is not outweighed by the risk. >15

Intensity-modulated radiotherapy + temozolomide improves quality of life in among grade III glioma with minimal toxicity Intensity-modulated radiotherapy + temozolomide has been shown to improve quality of life in grade III glioma, with minimal treatment-related toxicity and better quality of life, results of a prospective, single-centre comparative trial show. D eepa Gupta, MD, of the Medanta Cancer Institute, Medanta the Medicity, Gurgaon, India, explained that she and colleagues set out to evaluate grade III gliomas treated in the era of intensity-modulated radiotherapy and concurrent, adjuvant temozolomide in terms of early clinical outcome, prognostic factors, and quality of life. Fifty-three patients with anaplastic oligodendroglioma (n=25), anaplastic astrocytoma (n=18), or anaplastic oligoastrocytoma (n=10) were treated with intensity- modulated radiotherapy and concurrent (95%) and adjuvant temozolomide (90%). Data on 1p19q codeletion was available for 13 patients. Eighty percent had a Karnofsky performance score at least 90 with 30% experiencing seizures. Postoperative MRI was available in 65% cases and the intensity-modulated radiotherapy dose was 60 Gy in 30 fractions. Posttreatment imaging was performed 1, 3, and 6 months post intensity-modulated radiotherapy and then every 3 months. European Organisation for Research and Treatment of Cancer quality of life scales C35 and BN20 were administered before starting intensity-modulated radiotherapy, at completion, and then at each follow-up appointment. Kaplan-Meier analysis was used to estimate progression-free and overall survival. Median follow-up was 25 months, with 2 year disease- free and overall survival 75% and 88%, respectively. Patients tolerated treatment well with only 5% symp- tomatic central nervous system and 8% symptomatic haematological toxicities. Ninety-five percent completed the concurrent temozolomide schedule. At the first, 1-month evaluation, 30.4% exhibited a complete response; at 3 months, 40%; and at 6 months, 43%. At 6 months, only 4 % demonstrated

Capecitabine monotherapy extends life and benefits patients age 70 years and older with metastatic breast cancer

S tephen Johnston, MD, of the Royal Marsden Hospital National Health Service Foundation Trust, Lon- don, UK, explained that capecitabine monotherapy is associated with a clinical benefit rate of 60% and median time to progression of 4 months in patients 65 years of age and older with metastatic breast cancer. Thirty percent, however, require a dose reduction due to toxicity. The starting dose and schedule for capecitabine at Dr Johnston’s institution is 2000 mg/m 2 on days 1–14, every 3 weeks. Older patients with a poor performance status, comorbidities, and/or moderate to severe renal impairment may start with a further dose reduction. If early Common Terminology Criteria for Adverse Events grade ≥ 2 toxicity occurs, a switch from 3-weekly to a week on/week off schedule is used to improve tolerance. Dr Johnston and colleagues set out to evaluate toxicity and efficacy of capecit- abine monotherapy in patients 70 years of age and older diagnosed with metastatic breast cancer. The primary endpoint was toxicity. Secondary endpoints were clini- cal benefit rate, time to progression, and overall survival. From 2013 to 2015, 77 patients age 70 years and older were identified from the institution’s pharmacy data base. They had received capecitabine monotherapy for metastatic breast cancer. Capecit- abine was first-line therapy in 65 patients (84%). Forty-three and 34 patients received 2000 mg/m 2 and less than 2000 mg/m 2 , respectively (25 patients, 1500 mg/m 2 and nine patients, 1000 mg/m 2 ).

Patients starting at a lower dose were older (79 vs 73 years, P < 0.001); had more moderate to severe renal impairment (16% vs 44%, P = 0.016); Eastern Cooperative Oncology Group performance status ≥ 2 (11% vs 26 %, P = 0.156) and de novo metastatic disease (17% vs 35%, P = 0.09). With respect to toxicity, eight patients (19%) in the 2000 mg/m 2 group had grade 3–4 toxicities versus one patient (3%) in the <2000 mg/m 2 group. Nine versus 91% in the <2000 mg/m 2 and 2000 mg/m 2 group, respectively, required dose reduc- tion. Forty-two percent in the 2000 mg/ m 2 versus 32% in the <2000 mg/m 2 group switched to week on/week off due to early toxicity. No treatment-related deaths were observed. The clinical benefit rate for the 2000 mg/m 2 and <2000 mg/m 2 groups was 67% vs 43%, respectively (P = 0.05). After a median follow-up of 28.1 months, the combined time to pro- gression was 8.2 months. Overall survival was 18.6 months. Time to progression was 11.7 and 6.2 months in the 2000 mg/ m 2 and <2000 mg/m 2 groups, respectively (difference not significant). Dr Johnston concluded that, in patients age 70 years and older, capecit- abine monotherapy at a starting dose of 2000 mg/m 2 or lower is associated with a median time to progression of 8.2 months and a clinical benefit rate of 43–67%. Toxicity can be managed by dose reduc- tions and switching to a week on/week off schedule, which enables continued treat- ment in those deriving clinical benefit.

In patients age 70 years and older with metastatic breast cancer, capecitabine monotherapy at a starting dose of 2000 mg/m 2 or lower has been associated with a median time to progression of 8.2 months and a clinical benefit rate of 43–67%, results of a retrospective analysis show.

progressive disease. At last follow-up, 46/53 patients were evaluable. Eight had died and 55% experienced stable disease or a complete response. On univariate analysis for disease-free survival, Karnofsky performance scale score at presentation >90 (P = 0.001) and response at 6 months (P = 0.02) were significant and for overall survival, Karnofsky performance scale score at presentation alone (P = 0.004). Gross total resection, no residual at postoperativeMRI, up to six cycles of adjuvant temozolomide, and complete response at 6 months were favourable in terms of both disease-free and overall survival. Histopathological types were not significant for disease-free and overall survival. Only three patients exhibited the 1p19q codeletion. Quality-of-life scale scores suggested a decline in mood and cognition, as well as fatigue and toileting difficulty initially and an improvement beyond 3 months. Dr Gupta concluded that intensity-modu- lated radiotherapy + temozolomide improved quality of life in grade III glioma with minimal treatment-related toxicity. Proper case selection employing molecular prognostic markers yet to be developed will identify groups expected to respond most favourably.

© ESMO 2016

PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY