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Guidelines regarding male breast cancer
The American Society of Clinical Oncology (ASCO) has released guidelines regarding the management of men with breast cancer [1]. Among the recommendations are that men with early hormone receptor-positive breast cancer should be offered adjuvant tamoxifen; those with a contraindication to tamoxifen may be offered a gonadotropin-releasing hormone agonist/antagonist plus aromatase inhibitor. Men with early-stage disease should not be treated with bone-modifying agents to prevent recurrence but could still receive these agents to prevent or treat osteoporosis. For men with metastatic disease, targeted systemic therapy may be used according to the same indications and combinations offered to women. Our approach to men with breast cancer is consistent with these guidelines.
First-line atezolizumab plus bevacizumab for unresectable hepatocellular cancer
Sorafenib monotherapy represents a standard first-line regimen for unresectable hepatocellular cancer (HCC). In a trial comparing sorafenib with the combination of the immune checkpoint inhibitor atezolizumab plus bevacizumab in over 500 previously untreated patients with no worse than Child-Pugh A cirrhosis, the immunotherapy combination doubled the objective response rate and improved both survival and progression-free survival [2]. Grade 3 or 4 adverse events occurred in more than 50 percent of patients in each group, but hypertension, pyrexia, transaminitis, and proteinuria were more frequent with combined therapy. Largely based on this study, the US Food and Drug Administration (FDA) approved atezolizumab plus bevacizumab for treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy. We reserve this approach for healthy patients with unresectable HCC who have no worse than Child-Pugh A cirrhosis, and who have not recurred following a liver transplantation.
PARP inhibitors for prostate cancer with homologous recombination repair deficiency
The US Food and Drug Administration has approved two poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib and rucaparib) for men with metastatic castration-resistant prostate cancer (mCRPC) and a germline or somatic alteration in a homologous recombination repair (HRR) gene. Approval of rucaparib was based on the phase II TRITON2 trial, which reported prostate-specific antigen (PSA) and objective response rates of 54 and 48 percent, respectively, in men with previously treated mCRPC and a somatic or germline BRCA1/2 mutation [3]. Approval of olaparib was based on the PROFOUND trial in which men with previously treated mCRPC and HRR deficiency who received olaparib had higher objective response rates and better radiographic progression-free survival compared with a second-generation hormone therapy (enzalutamide, abiraterone) [4]. Men with BRCA2 mutations appear to benefit the most from PARP inhibitors; however, all men with a germline or somatic mutation in an HRR gene (including BRCA1, BRCA2, CHEK2, ATM, PALB2, FANCA, RAD51B) may consider treatment with a PARP inhibitor at some point in their treatment.
Epstein-Barr virus (EBV) DNA as a biomarker in nasopharyngeal carcinoma
In patients with locoregional nasopharyngeal carcinoma (NPC), there is interest in using plasma Epstein-Barr virus (EBV) DNA levels as a biomarker for prognosis and surveillance. In one risk stratification model developed in approximately 800 patients with NPC, the addition of EBV DNA to tumor-lymph node-metastasis (TNM) stage identified low-risk patients who could potentially be spared the toxicity of adjuvant therapy [5]. In another retrospective study of approximately 2000 patients with NPC, posttreatment EBV DNA levels were associated with higher rates of disease recurrence, detected metastatic disease with high sensitivity and specificity, and identified recurrences prior to radiographic or clinical evidence of disease [6]. While promising, further prospective data confirming a survival benefit are needed before incorporating posttreatment EBV DNA levels into the routine management of these patients.
Cemiplimab in locally advanced cutaneous squamous cell carcinoma
Cemiplimab, a programmed cell death-1 protein (PD-L1) checkpoint inhibitor, is approved for use in patients with advanced or metastatic cutaneous squamous cell carcinoma (SCC) ineligible for curative resection or radiation therapy. However, its efficacy in those with locally advanced unresectable cutaneous SCC (ie, locally invasive tumor without nodal or distant metastases) is not established. In an open-label phase II trial of approximately 80 patients with locally advanced cutaneous SCC, at median follow-up of nine months, cemiplimab demonstrated an objective response rate of 44 percent, including complete and partial response rates of 13 and 31 percent, respectively [7]. Based on these data, we suggest the use of cemiplimab in patients with locally advanced cutaneous SCC who are ineligible for curative surgery or radiation therapy, rather than other systemic agents.
1. Hassett MJ, Somerfield MR, Baker ER, et al. Management of Male Breast Cancer: ASCO Guideline. J Clin Oncol 2020; 38:1849.
2. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med 2020; 382:1894.
3. Abida W, Campbell D Patnaik A, et al. Preliminary results from the TRITON2 study of rucaparib in patients with DNA damage repair (DDR)-deficient metastatic castration-resistant prostate cancer (mCRPC): Updated analyses (abstract 846PD). Data presented at the 2019 European Society for Medical Oncology (ESMO) Congress, September 29, 2019, Barcelona, Spain. Abstract available online at https://cslide.ctimeetingtech.com/esmo2019/attendee/confcal/session/calendar?q=T (Accessed on October 28, 2019).
4. Hussain M, Mateo J, Fizazi K, et al. PROfound: Phase III study of olaparib versus enzalutamide or abiraterone for metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) gene alterations (LBA12_PR). Data presented at the European Society for Medical Oncology Congress; Sept 30, 2019, Barcelona, Spain. Abstract available online at https://oncologypro.esmo.org/Meeting-Resources/ESMO-2019-Congress/PROfound-Phase (Accessed on October 03, 2019).
5. Hui EP, Li WF, Ma BB, et al. Integrating postradiotherapy plasma Epstein-Barr virus DNA and TNM stage for risk stratification of nasopharyngeal carcinoma to adjuvant therapy. Ann Oncol 2020.
6. Chen FP, Huang XD, Lv JW, et al. Prognostic potential of liquid biopsy tracking in the posttreatment surveillance of patients with nonmetastatic nasopharyngeal carcinoma. Cancer 2020; 126:2163.
7. Migden MR, Khushalani NI, Chang ALS, et al. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Lancet Oncol 2020; 21:294.
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