PracticeUpdate Oncology Best of 2018

EDITOR’S PICKS 11

Pathological Response and Survival in TNBC After Neoadjuvant Carboplatin + Docetaxel Take-home message • This study looked at recurrence-free and overall survival according to the degree of pathologic response in patients with stage I–III triple-negative breast cancer treated with neoadjuvant carboplatin plus docetaxel. The rate of pathological complete response (pCR) was 55%. The rate of residual cancer burden class I was 13%. At 3 years, overall survival for patients with pCR was 94% vs 79% for those without pCR. • These results indicate that neoadjuvant carboplatin plus docetaxel shows promise in extending survival in patients with triple-negative breast cancer. Neil Majithia MD Clinical Cancer Research

and pertuzumab plus metronomic oral cyclo- phosphamide (hazard ratio [HR] 0·65 [95% CI 0·37-1·12], p=0·12). At a median follow-up of 20·7 months (IQR 12·5-30·4), the median progression-free survival was 5·6 months (95% CI 3·6-16·8) with trastuzumab and pertu- zumab versus 12·7 months (6·7-24·8) with the addition of metronomic oral cyclophospha- mide. The most frequent grade 3-4 adverse events were hypertension (in six [15%] of 39 patients in the trastuzumab and pertuzumab group vs five [12%] of 41 in the trastuzumab and pertuzumab plus metronomic oral cyclo- phosphamide group), diarrhoea (four [10%] vs five [12%]), dyspnoea (two [5%] vs four [10%]), fatigue (three [8%] vs two [5%]), pain (two [5%] vs two [5%]), and a thromboembolic event (0 [0%] vs four [10%]). Severe cardiac toxicities were occasionally observed in both groups. In the trastuzumab and pertuzumab group four patients died without progression, due to cardiac arrest during treatment (n=1), peri- toneal infection (n=1), respiratory failure (n=1), and sudden death without a specified cause (n=1). In the trastuzumab and pertuzumab plus metronomic oral cyclophosphamide group, one patient died from heart failure. INTERPRETATION Addition of metronomic oral cyclophosphamide to trastuzumab plus pertuzumab in older and frail patients with HER2-positive metastatic breast can- cer increased median progression-free survival by 7 months compared with dual HER2 blockade alone, with an acceptable safety profile. Trastuzumab and pertuzumab plus metronomic oral cyclophosphamide, followed by trastuzumab emtansine after disease progression, might delay or super- sede the need for taxane chemotherapy in this population. Pertuzumab and Trastuzumab With or Without Metronomic Chemotherapy for Older Patients With HER2-Positive Meta- static Breast Cancer (EORTC 75111-10114): An Open-Label, Randomised, Phase 2 Trial From the Elderly Task Force/Breast Can- cer Group. Lancet Oncol 2018 Feb 09;[EPub Ahead of Print], HWildiers, K Tryfonidis, L Dal Lago, et al. www.practiceupdate.com/c/64062

Abstract PURPOSE Prognostic value of pathologic com- plete response (pCR) and extent of pathologic response attained with anthracycline-free plat- inum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free sur- vival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC. EXPERIMENTAL DESIGN One-hundred and ninety patients with stage I-III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m 2 ) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Resid- ual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan-Meier method. RESULTS Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracy- clines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14-0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10-0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS. CONCLUSIONS Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regi- men demonstrate excellent 3-year RFS and OS without adjuvant anthracycline. Pathological Response and Survival in Triple-Negative Breast Cancer Following Neo- adjuvant Carboplatin Plus Docetaxel. ClinCancer Res 2018 Sep 26;[EPub Ahead of Print], P Sharma, S López-Tarruella, JA García-Saenz, et al. www.practiceupdate.com/c/73994

COMMENT By Lee S. Schwartzberg MD, FACP T he pCR rate from neoadjuvant chemotherapy for triple-negative breast cancer (TNBC) is enhanced by adding a platinum agent like carbo- platin but at the cost of additional toxicity when added to the traditional backbone of anthracycline, cyclophosphamide, and taxane. The authors of this study have previously presented a phase II study of carboplatin and docetaxel in TNBC, and the results are updated in Clinical Cancer Research for 3-year DFS and OS. There was an impressive pCR rate of 55% with this combination, with low incidence of grade 3/4 toxicity. Note that all patients received prophylactic growth factor support. The 3-year DFS for patients who had a pCR or a resid- ual cancer burden (RCB) of I was 91%, and the 3-year OS was 95%. Although a two-institution clinical trial single-arm study has to be replicated in a phase III setting, the regimen is the backbone of the TCH regimen and is familiar to almost everyone. It offers a potentially higher pCR rate and, impor- tantly, an improved clinical outcome compared with docetaxel and cyclo- phosphamide with similar toxicity, and takes advantage of the DNA repair defi- ciency that is present in many TNBCs, not limited only to BRCA1/2 mutation carriers. For TNBC patients who are not candidates for anthracyclines but who are at a higher risk of relapse (node-positive, larger tumors), this is an attractive regimen.

VOL. 2 • NO. 4 • 2018