PracticeUpdate: Haematology & Oncology

BREAST

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Low to modest reductions in neutropenia-related hospitalisations observed with colony-stimulating factors Comment by Lee Schwartzberg, MD, FACP G rowth factor support with granulocyte-colony stimulat- ing factor (G-CSF) reduces

cancer setting with three common regimens: TC, TCH, and non-dose dense AC. The investigators found that the TC and TCH regimens plus G-CSF, overwhelmingly adminis- tered as long-acting pegfilgrastim, were associated with a reduction in hospitalisation. In contrast, women taking AC, a regimen considered

But, which patients receiving inter- mediate-risk regimens, with a 10% to 20% risk of febrile neutropenia, deserve G-CSF prophylaxis and what are the clinical and economic benefits of the intervention? This retrospective claims-based study adds an important analysis of use of growth factor in the breast

low risk by guidelines, did not derive benefit from growth factor. In the TC/TCH groups, the re- duction in hospitalisation benefit was pronounced in older patients (>65 years of age) who received prophylaxis. This finding is very much in keeping with guidelines, which suggest, for intermediate-risk regimens, that patient risk factors are very important to consider. Risk factors include age, comorbidi- ties, prior history of neutropenia, and prior chemotherapy. While for the overall group analysed in this study the strict cost–benefit ratio was modest, the clinician who ap- plies the principles of judiciously using growth factor support with moderate-risk regimens will reduce the adverse events associated with chemotherapy in breast cancer and likely do so in a cost-effective, re- sponsible manner.

the incidence of febrile neutropenia, hospitalisation, and death in patients at high risk of myelosuppression from chemotherapy, which is com- monly considered at a threshold lev- el of >20% risk without prophylaxis.

Risk of neutropenia-related hospitalization in patients who received colony-stimulating factors with chemotherapy for breast cancer Journal of Clinical Oncology Take-home message • The authors evaluated 4815 patients with breast cancer who received docetaxel and cyclophosphamide (TC), docetaxel, carboplatin, and trastuzumab (TCH), and doxorubicin and cyclophosphamide (AC) to determine if granulocyte–colony stimulating factor (G-CSF) prophylaxis improved neutropenia-related hospitalizations. Results showed that G-CSF given within 5 days of starting chemotherapy was associated with reduced risk of neutropenia-related hospitalization in patients taking TC (adjusted OR, 0.29) and in those taking THC (adjusted OR, 0.19) but not in those taking AC (adjusted OR, 1.21). • There was a low to modest benefit relative to neutropenia-related hospitalizations associated with G-CSF prophylaxis in breast cancer patients being treated with TC and TCH. Abstract

or infection-related hospitalization within 21 days of initiating chemotherapy. Multivariable regressions and number-needed-to-treat analyses were used. RESULTS A total of 4,815 patients received TC (2,849 PP; 1,966 no PP); 2,292 patients received TCH (1,444 PP; 848 no PP); and 1,638 patients received AC (857 PP; 781 no PP) regimen. PP was associated with reduced risk of neutropenia-related hospitalization for TC (2.0% PP; 7.1% no PP; adjusted odds ratio [AOR], 0.29; 95% CI, 0.22 to 0.39) and TCH (1.3% PP; 7.1% no PP; AOR, 0.19; 95% CI, 0.12 to 0.30), but not AC (4.7% PP; 3.8% no PP; AOR, 1.21; 95% CI, 0.75 to 1.93) regimens. For the TC regimen, 20 patients (95% CI, 16 to 26) would have to be treated for 21 days to avoid one neutropenia-related hospitalization; with the TCH regimen, 18 patients (95% CI, 13 to 25) would have to be treated. CONCLUSION Primary G-CSF prophylaxis was associated with low-to-modest benefit in lowering neutropenia- related hospitalization in patients with breast cancer who received TC and TCH regimens. Further evaluation is needed to better understand which patients benefit most from G-CSF prophylaxis in this setting. J Clin Oncol 2016 Sep 19;[Epub ahead of print], Agiro A, Ma Q, Acheson AK, et al.

database for 14 commercial US health plans. This retrospective analysis included patients with breast cancer who began first-cycle chemotherapy from 2008 to 2013 using docetaxel and cyclophosphamide (TC); docetaxel, carboplatin, and trastuzumab (TCH); or doxo- rubicin and cyclophosphamide (conventional-dose AC) regimens. Primary prophylaxis (PP) was defined as G-CSF administration within 5 days of beginning chemotherapy. Outcome was neutropenia, fever,

Dr Schwartzberg is Senior Partner

PURPOSE To describe outcomes after granulocyte colony-stimulating factor (G-CSF) prophylaxis in pa- tients with breast cancer who received chemotherapy regimens with low-to-intermediate risk of induction of neutropenia-related hospitalization. PATIENTS AND METHODS We identified 8,745 patients age ≥ 18 years from a medical and pharmacy claims

and Medical Director, The West Clinic, Memphis, Tennessee.

Dual block with lapatinib and trastuzumab effective as neoadjuvant treatment of HER2-postive breast cancer Comment by Lee Schwartzberg, MD, FACP A ddition of lapatinib, a small-molecule HER2 inhibitor, to trastuzumab with chemotherapy led to improvement lapatinib, and finds that its biggest impact is in the ER− subgroup and those patients receiving single-agent taxane. In an era when combina- tion chemotherapy is typically delivered with

anti-HER2 agents, the incremental benefit of lapatinib is small and nonsignificant. However, given the growing use of single-agent taxane plus trastuzumab in lower-risk patients or patients with more comorbidities, one can conjecture a setting in which adding lapatinib instead of more cytotoxic chemotherapy would make sense in the neoadjuvant/adjuvant set- ting. It would be interesting to see a prospec- tive trial test this idea.

in the pathologic complete response rate in the neoadjuvant setting but not disease-free survival benefit in the adjuvant setting. This meta-analysis teases out the relative benefit of

Dual block with lapatinib and trastuzumab vs single-agent trastuzumab combined with chemotherapy as neoadjuvant treatment of HER2-positive breast cancer: a meta-analysis of randomized trials Clinical Cancer Research Take-home message

Advances in genomic testing and computational biology for breast cancer

672 (58.2%) hormone receptor- positive, 534 (46.2%) received taxanes alone, and 621 (53.8%) anthracyclines plus taxanes or the docetaxel-carboplatin regi- men. Overall, the dual block was associated with a significant 13% absolute improvement in pCR rate compared with single-agent tras- tuzumab (summary risk difference, SRD 0.13; 95% CI, 0.08–0.19). The activity was greater in hormone receptor-negative patients who received chemotherapy with taxanes alone (SRD 0.25; 95% CI, 0.13–0.37), compared to hor- mone receptor-positive or hor- mone receptor-negative disease treated with anthracyclines plus taxanes or the docetaxel-carbo- platin regimen (SRD 0.09; 95% CI, 0.02–0.15; Pinteraction = 0.05). CONCLUSIONS On the basis of ΔpCR data, the dual block with trastuzumab and lapatinib plus chemotherapy is a very active treatment only in HER2(+) and hormone receptor-negative breast cancer treated with taxane monochemotherapy. Clin Cancer Res 2016;22:4594- 4603, Clavarezza M, Puntoni M, Gennari A, et al.

• This meta-analysis assessed neoadjuvant combination of lapa- tinib and trastuzumab vs trastuzumab alone in HER2-positive breast cancer. The combination was associated with a 13% absolute improvement in pathologic complete response com- pared with trastuzumab alone (summary risk difference, 0.13). Interestingly, in hormone receptor-negative patients, there was greater activity with trastuzumab alone compared with the hormone receptor-positive or hormone receptor-negative patients treated with the dual block. • The authors conclude that patients with HER2-positive breast cancer benefit from the neoadjuvant combination of lapatinib and trastuzumab, while hormone receptor–negative patients demonstrate the best results with taxane monotherapy. Abstract

INTERVIEW WITH KIMBERLY BLACKWELL, MD

Dr Blackwell discusses the latest advances in genomic testing and gene expression profiles, in- cluding results of the MINDACT trial and immune

checkpoint inhibitors. Dr Blackwell is Professor of Medicine and Assis- tant Professor in Radiation Oncol- ogy, Duke Department of Medicine, North Carolina.

HER2 biosimilars in clinical practice: an interviewwith Dr William Gradishar INTERVIEW WITH WILLIAM GRADISHAR, MD, FACP

trastuzumab versus trastuzumab alone in HER2+ breast cancer. EXPERIMENTAL DESIGN Trials were identified by Medline (PubMed), ISI Web of Science (Science Cita- tion Index Expanded), Embase, Cochrane library, and reference lists of published studies, review articles, editorials, and by hand- searched reports from major cancer meeting reports. RESULTS Six randomized trials including 1,155 patients were identified, of whom 483 (41.8%) were hormone receptor-negative,

PURPOSE (Neo)adjuvant treat- ment with chemotherapy plus trastuzumab reduces recurrence and death risk in HER2-positive (HER2+) breast cancer. Rand- omized trials assessed HER2 dual block by adding lapatinib to trastuzumab and chemotherapy in the neoadjuvant setting using pathologic complete response (pCR) as the outcome measure. We conducted a meta-analysis of randomized trials testing neoadju- vant dual block with lapatinib and

Dr Gradishar discusses the Heritage trial on the trastuzumab biomimilar for HER2+ metastatic breast cancer and shares his thoughts on using biosimilars in practice. Dr Gradishar is Betsy Bram-

sen Professor of Breast Oncology in the Division of Hematology and Medical Oncology, Department of Medicine, at the Feinberg School Medicine at Northwestern Univer- sity in Chicago, Illinois.

VOL. 1 • No. 4 • 2016