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Introduction: Overall prognosis of early TNBC remains inferior to that of other breast cancer subtypes. Neoadjuvant platinum added to taxanes-anthracycline regimen has been reported to potentially improve pathologic complete response (pCR) and survival in TNBC pts. Aim: To report the final results of the efficacy and toxicity of the addition of weekly Cp to P and dose dense (dd) EC on the pCR rate in an open-label phase II study in stage II/III TNBC pts. Patients and methods: In the BSMO study sixty three pts received dd P (80mg/m2/wk) concurrent with Cp (AUC=2) for 12 weeks, added to bi-weekly E (90mg/m2) and C (600mg/m2) for 4 cycles, followed by surgery and radiotherapy. The primary endpoint was pCR in the breast and axilla. Additionally actual drug dosing and toxicities were registered. A correlative assessment of germline mutations in HRD genes is ongoing. Pts were monitored for clinical response by magnetic resonance and mammography, and also for relapse free survival and time to treatment failure. The study sample size has been calculated according to the optimal Simon's two-stage design method. The target sample size was 63 patients with 80% power to detect a pCR rate of > or=47% (α= 0.05). Results: Sixty three eligible pts with operable, non-inflammatory stage II/III TNBC were included. Most pts were between 40 and 59 yrs old and had clinical stage II disease. Forty percent were clinically node + and 68% were G3. Seventy three percent received breast conserving surgery. Sixty percent (38 out of 63 pts) achieved a pCR breast/axilla. Sixteen percent (10pts) missed three or more doses of wP, whereas at least 1 EC cycle was skipped in 19% (12pts). Sixty five percent had G3/4 neutropenia. Investigator reported febrile neutropenia occurred in 18 pts (28.5%) of which more than eighty percent during the EC part despite primary prophylaxis. Thrombocytopenia G3/4 was noticed in 10 pts (16%). Only four pts (6%) developed grade 3 peripheral neuropathy. Conclusion: The addition of weekly carboplatinum to neoadjuvant paclitaxel and ddEC is feasible and a pCR rate in the breast and axilla as high as 60% compares nicely with the results achieved with the similar 3 weekly carboplatinum arm of the CALBG 40603 trial. Febrile neutropenia rate was higher than the 3-weekly carboplatin arm in CALGB40603 trial, but occurred mainly during the EC part, while other toxicities are comparable. Future research could focus on this combination in the reverse sequence (first ECdd), which may lead to a better global haematological profile. Citation Format: Fontaine C, Cappoen N, Renard V, Van Den Bulck H, Vuylsteke P, Glorieux P, Dopchie C, Decoster L, De Grève J, Awada A, Wildiers H. Final results of weekly (w) neoadjuvant carboplatin (Cp) added to paclitaxel (P) followed by epirubicin (E) and cyclophosphamide (C) in triple negative breast cancer (TNBC) patients (pts): A BSMO breast cancer task force phase II study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-09.

Introduction: Triple negative breast cancer (TNBC) remains a challenging disease with dismal prognosis. Platinum analogs have not yet shown to improve long term outcome in this setting, but are associated with increased pathological complete response rate (pCR) at the cost of higher toxicity. Aim: To further increase or maintain the high pCR rate with platinum containing schedules while decreasing toxicity by administering low dose weekly carboplatin instead of high-dose 3 weekly carboplatin as in CALGB 40603.(1) Patients and methods: We evaluated the tolerability and the impact of the addition of weekly carboplatin (CP) to paclitaxel (P) and dose dense epirubicin-cyclofosfamide (EC) on pCR in an open-label multicenter phase II study in stage II/III TNBC patients (pts). Sixty three pts received dose dense paclitaxel (P:80mg/m2/wk) concurrent with carboplatin (CP: AUC=2) for 12 wks, followed by two-weekly epirubicin (E:90mg/m2) and cyclophosphamide (C:600mg/m2) for 4 cycles. The primary endpoint is pCR in the breast and axilla. Additionally treatment deliveryand adverse events are recorded. A correlative assessment of germline mutations in homologous recombination (HR) genes is planned. Pts are monitored for response by magnetic resonance and mammography and also for relapse free survival and time to treatment failure. The study size sample has been calculated according to the optimal Simon's two-stage design method. The target sample size was 63 patients with 80% power to detect a pCR rate of ≥47% (α= 0.05). Results: Accrual to the study is completed with 63 eligible pts with operable, noninflammatory stage II and III TNBC included. Most patients were between 40 and 60 yrs old and were clinical stageT2 tumors. Half of the pts were clinically node + and 70% were G3. Sixty six percent had breast conserving surgery. Sixteen out of 26 (61.5%) of the currently evaluable pts achieved a pCR rate in the breast and axilla. The other ongoing patients have not yet reached this endpoint. Four out of 21 evaluable pts that completed the chemotherapy missed two or more doses of CP due to neutropenia(NP) G3/4(2), general deterioration G3(1) and polyneuropathy(PNP) G3(1) and seven pts needed one dose reduction of P and/or CP due to NP G3-4 (3-2) and PNP G2(1) and one abdominal infection. Conclusion: These preliminary data suggest that the addition of weekly carboplatinum to neoadjuvant paclitaxel and EC is feasible and has a promising pCR rate in the breast and axilla as high as 61.5% in early TNBC pts. More mature toxicity and outcome data and correlation with genome analysis will be presented. (1) Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once per week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603(Alliance) Sikov WM et al. J Clin Oncol 33:13-21; 2014. Citation Format: Fontaine C, Cappoen N, Renard V, Vuylsteke P, Van Den Bulck H, Glorieux P, t'Kint de Roodenbeke D, Dopchie C, Decoster L, Vanacker L, De Grève J, Awada A, Wildiers H. Neoadjuvant weekly carboplatin and paclitaxel followed by dose dense epirubicin and cyclophosphamide in triple negative breast cancer patients: A single arm phase II study from the Belgian Society of Medical Oncology [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-06.

Lung cancer is the number one cause of cancer-related death worldwide with cigarette smoking as its major risk factor. Although the incidence of lung cancer in never smokers is rising, this subgroup of patients is underrepresented in genomic studies of lung cancer. Here, we assembled a prospective cohort of 46 never-smoking, nonsmall cell lung cancer (NSCLC) patients and performed whole-exome and low-coverage whole-genome sequencing on tumors and matched germline DNA. We observed fewer somatic mutations, genomic breakpoints and a smaller fraction of the genome with chromosomal instability in lung tumors from never smokers compared to smokers. The lower number of mutations, enabled us to identify TSC22D1 as a potential driver gene in NSCLC. On the other hand, the frequency of mutations in actionable genes such as EGFR and ERBB2 and of amplifications in MET were higher, while the mutation rate of TP53, which is a negative prognostic factor, was lower in never smokers compared to smokers. Together, these observations suggest a more favorable prognosis for never smokers with NSCLC. Classification of somatic mutations into six-substitution type patterns or into 96-substitution type signatures revealed distinct clusters between smokers and never smokers. Particularly, we identified in never smokers signatures related to aging, homologous recombination damage and APOBEC/AID activity as the most important underlying processes of NSCLC. This further indicates that second-hand smoking is not driving NSCLC pathogenesis in never smokers. ispartof: INTERNATIONAL JOURNAL OF CANCER vol:146 issue:11 pages:3207-3218 ispartof: location:United States status: published

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TPS2615Background: Next generation sequencing of solid tumors will increasingly reveal mutations in cancer genes, including EGFR, HER2 and HER3 mutations. Afatinib is a small molecule, which select...