Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity.

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BackgroundMany methodologies have been used in research to identify the “intrinsic” subtypes of breast cancer commonly known as Luminal A, Luminal B, HER2-Enriched (HER2-E) and Basal-like. The PAM50 gene set is often used for gene expression-based subtyping; however, surrogate subtyping using panels of immunohistochemical (IHC) markers are still widely used clinically. Discrepancies between these methods may lead to different treatment decisions.MethodsWe used the PAM50 RT-qPCR assay to expression profile 814 tumors from the GEICAM/9906 phase III clinical trial that enrolled women with locally advanced primary invasive breast cancer. All samples were scored at a single site by IHC for estrogen receptor (ER), progesterone receptor (PR), and Her2/neu (HER2) protein expression. Equivocal HER2 cases were confirmed by chromogenic in situ hybridization (CISH). Single gene scores by IHC/CISH were compared with RT-qPCR continuous gene expression values and “intrinsic” subtype assignment by the PAM50. High, medium, and low expression for ESR1, PGR, ERBB2, and proliferation were selected using quartile cut-points from the continuous RT-qPCR data across the PAM50 subtype assignments.ResultsESR1, PGR, and ERBB2 gene expression had high agreement with established binary IHC cut-points (area under the curve (AUC) ≥ 0.9). Estrogen receptor positivity by IHC was strongly associated with Luminal (A and B) subtypes (92%), but only 75% of ER negative tumors were classified into the HER2-E and Basal-like subtypes. Luminal A tumors more frequently expressed PR than Luminal B (94% vs 74%) and Luminal A tumors were less likely to have high proliferation (11% vs 77%). Seventy-seven percent (30/39) of ER-/HER2+ tumors by IHC were classified as the HER2-E subtype. Triple negative tumors were mainly comprised of Basal-like (57%) and HER2-E (30%) subtypes. Single gene scoring for ESR1, PGR, and ERBB2 was more prognostic than the corresponding IHC markers as shown in a multivariate analysis.ConclusionsThe standard immunohistochemical panel for breast cancer (ER, PR, and HER2) does not adequately identify the PAM50 gene expression subtypes. Although there is high agreement between biomarker scoring by protein immunohistochemistry and gene expression, the gene expression determinations for ESR1 and ERBB2 status was more prognostic.

Induction chemotherapy with PCF was better tolerated and resulted in a higher CR rate than CF. However, new trials that compare induction chemotherapy plus CRT versus CRT alone are needed to better define the role of neoadjuvant treatment.

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Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.

Background: Triple negative breast cancers of high proliferation or grade are a subgroup characterized by very poor prognosis, rapid progression to metastatic stage and rapid onset of resistance to chemotherapy after initial response. As a whole, triple negative breast cancer (TNBC) represents a specific area of medical need, in which new therapeutic approaches deserve appropriate test. Retrospective data showed that a subset of patients have an ongoing immune response within the tumor microenvironment, and that PD-L1 expression is an adaptive method of tumor resistance to tumor infiltrating lymphocytes, which in turn are needed for response to chemotherapy. Overall, the data suggests a role for immune regulation of response to chemotherapy, and support the concept that blockade of immune check-points may favor the achievement of durable response by immune mechanisms themselves, and in combination with classical chemotherapy. Methods: In this multicenter open label study (NCT002620280), a total of 280 patients with TNBC were randomized to neoadjuvant carboplatin AUC 2 and abraxane 125 mg/m2 iv on days 1 and 8, with or without atezolizumab 1200 mg iv on day 1. Both regimens were given every 3 weeks for 8 cycles and were followed by surgery and by 4 cycles of an anthracycline regimen as per investigator choice. The primary aim of the study is to compare event-free survival 5 years after randomization of the last patient. Important secondary aim is the rate of pCR (defined as absence of invasive in breast and lymph nodes). The comparison among treatments will be carried out by a two-sided Cochran-Mantel-Haenszel test, controlling for disease stage (early high-risk vs locally advanced) and PD-L1 expression (positive vs negative). The primary population for all efficacy endpoints will be the ITT (intent-to-treat) population, the safety population is defined as all randomized patients who received at least one dose of either regimen. pCR and safety data will be presented at the meeting. Patients will continue to be followed up to allow for assessing comparative long-term event-free and overall survival analyses. Supported in part by unrestricted grants from Hoffman-La Roche, Ltd, Switzerland and Celgene International Sarl, Switzerland Citation Format: Luca Gianni, Chiun-Sheng Huang, Daniel Egle, Begona Bermejo, Claudio Zamagni, Marc Thill, Antonio Anton, Stefania Zambelli, Giampaolo Bianchini, Stefania Russo, Eva Ciruelos, Richrad Greil, Vladimir Semiglazov, Marco Colleoni, Catherine Kelly, Gabriella Mariani, Lucia Del Mastro, Ilaria Maffeis, Pinuccia Valagussa, Giuseppe Viale. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple negative, early high-risk and locally advanced breast cancer. NeoTRIPaPDL1 Michelangelo randomized study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS3-04.

The Oncologist 2012;17:15-25 www.TheOncologist.com Patients and Methods. Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety.Results. The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n ‫؍‬ 239; bevacizumab, n ‫؍‬ 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0 -53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand-foot syndrome, and neuropathy. Conclusion. Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with singleagent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients. The Oncologist 2012;17:15-25