Paul Marcom

Overview:

Basic Science:
-Germline and somatic genetic changes in breast cancer.

Translational:
-Identification and management of individuals and families with hereditary cancer risk.
-Communication of cancer risk information to individuals and families.
-Breast cancer prevention.
-Optimizing management of early breast cancer.
-Treatment of metastatic breast cancer


Clinically, Dr. Marcom works as a medical oncologist in the multidisciplinary breast cancer clinic. He participates in clinical trials investigating new chemotherapeutic and biologic treatments. 

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1989

Baylor University

Medical Resident, Medicine

Duke University

Fellow in Hematology-Oncology, Medicine

Duke University

Grants:

Targeting nuclear FGF receptor to improve chemotherapy response in triple-negative breast cancer

Administered By
Pathology
Awarded By
Department of Defense
Role
Investigator
Start Date
End Date

Kastan Gray Foundation Project

Administered By
Duke Cancer Institute
Role
Researcher
Start Date
End Date

Randomized Trial of Optimal Type of Aerobic Training in Breast Cancer

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Markers of short term breast cancer risk in FNA

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Phase II trial of Cetuximab & Carboplatin in Basal-like Breast Cancer

Administered By
Surgery
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Publications:

TBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial).

PURPOSE:Platinum compounds have activity in triple-negative breast cancer (TNBC) in germline BRCA mutation carriers (BRCA carriers). Limited data exist for estrogen receptor (ER)-positive (+) breast cancer among BRCA carriers. INFORM is a randomized, multicenter, phase II trial comparing pathologic complete response (pCR) rates (ypT0/is, N0) after neoadjuvant single-agent cisplatin (CDDP) versus doxorubicin-cyclophosphamide (AC) in BRCA carriers with stage I-III human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Secondary objectives included residual cancer burden scores (RCB) of 0 or 1 (combined) and toxicity. The goal was to determine whether pCR was ≥ 20% higher with CDDP than AC. PATIENTS AND METHODS:BRCA carriers with cT1-3 (≥ 1.5 cm), cN0-3 HER2-negative breast cancer were randomly assigned to preoperative CDDP (75 mg/m2 every 3 weeks × 4 doses) or AC (doxorubicin 60 mg/m2; cyclophosphamide 600 mg/m2 every 2-3 weeks × 4 doses) followed by surgery. Pathologic responses were confirmed by central review. RESULTS:A total of 118 patients were randomly assigned; 117 were included in outcome analyses. Mean age was 42 years (range, 24-73 years); 69% were BRCA1+, 30% were BRCA2+, and 2% had both mutations. Clinical stage was I for 19%, II for 63%, and III for 18%; 45% had nodal involvement at baseline. Seventy percent had TNBC. Clinical and tumor characteristics were well matched between treatment arms. The pCR rate was 18% with CDDP and 26% with AC, yielding a risk ratio (RR) of 0.70 (90% CI, 0.39 to 1.2). The risk of RCB 0 or 1 (RCB 0/1) was 33% with CDDP and 46% with AC (RR, 0.73; 90% CI, 0.50 to 1.1). Both regimens were generally well tolerated without unexpected toxicities. CONCLUSION:pCR or RCB 0/1 is not significantly higher with CDDP than with AC in BRCA carriers with stage I-III HER2-negative breast cancer for both TNBC and ER+/HER2-negative disease.
Authors
Tung, N; Arun, B; Hacker, MR; Hofstatter, E; Toppmeyer, DL; Isakoff, SJ; Borges, V; Legare, RD; Isaacs, C; Wolff, AC; Marcom, PK; Mayer, EL; Lange, PB; Goss, AJ; Jenkins, C; Krop, IE; Winer, EP; Schnitt, SJ; Garber, JE
MLA Citation
Tung, Nadine, et al. “TBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial).Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 38, no. 14, May 2020, pp. 1539–48. Epmc, doi:10.1200/jco.19.03292.
URI
https://scholars.duke.edu/individual/pub1433326
PMID
32097092
Source
epmc
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
38
Published Date
Start Page
1539
End Page
1548
DOI
10.1200/jco.19.03292

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

Several new systemic therapy options have become available for patients with metastatic breast cancer, which have led to improvements in survival. In addition to patient and clinical factors, the treatment selection primarily depends on the tumor biology (hormone-receptor status and HER2-status). The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.
Authors
Gradishar, WJ; Anderson, BO; Abraham, J; Aft, R; Agnese, D; Allison, KH; Blair, SL; Burstein, HJ; Dang, C; Elias, AD; Giordano, SH; Goetz, MP; Goldstein, LJ; Isakoff, SJ; Krishnamurthy, J; Lyons, J; Marcom, PK; Matro, J; Mayer, IA; Moran, MS; Mortimer, J; O'Regan, RM; Patel, SA; Pierce, LJ; Rugo, HS; Sitapati, A; Smith, KL; Smith, ML; Soliman, H; Stringer-Reasor, EM; Telli, ML; Ward, JH; Young, JS; Burns, JL; Kumar, R
MLA Citation
Gradishar, William J., et al. “Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.Journal of the National Comprehensive Cancer Network : Jnccn, vol. 18, no. 4, Apr. 2020, pp. 452–78. Epmc, doi:10.6004/jnccn.2020.0016.
URI
https://scholars.duke.edu/individual/pub1437155
PMID
32259783
Source
epmc
Published In
Jnccn Journal of the National Comprehensive Cancer Network
Volume
18
Published Date
Start Page
452
End Page
478
DOI
10.6004/jnccn.2020.0016

The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial.

BACKGROUND: Previous data suggest that the immune microenvironment plays a critical role in human epidermal growth factor receptor 2 (HER2) -positive breast cancer; however, there is little known about the immune profiles of small HER2-positive tumors. In this study, we aimed to characterize the immune microenvironment of small HER2-positive breast cancers included in the Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer (APT) trial and to correlate the immune markers with pathological and molecular tumor characteristics. PATIENTS AND METHODS: The APT trial was a multicenter, single-arm, phase II study of paclitaxel and trastuzumab in patients with node-negative HER2-positive breast cancer. The study included 406 patients with HER2-positive, node-negative breast cancer, measuring up to 3 cm. Exploratory analysis of tumor infiltrating lymphocytes (TIL), programmed death-ligand 1 (PD-L1) expression (by immunohistochemistry), and immune gene signatures using data generated by nCounter PanCancer Pathways Panel (NanoString Technologies, Seattle, WA), and their association with pathological and molecular characteristics was carried out. RESULTS: Of the 406 patients, 328 (81%) had at least one immune assay carried out: 284 cases were evaluated for TIL, 266 for PD-L1, and 213 for immune gene signatures. High TIL (≥60%) were seen with greater frequency in hormone-receptor (HR) negative, histological grades 2 and 3, as well in HER2-enriched and basal-like tumors. Lower stromal PD-L1 (≤1%) expression was seen with greater frequency in HR-positive, histological grade 1, and in luminal tumors. Both TIL and stromal PD-L1 were positively correlated with 10 immune cell signatures, including Th1 and B cell signatures. Luminal B tumors were negatively correlated with those signatures. Significant correlation was seen among these immune markers; however, the magnitude of correlation did not indicate a monotonic relationship between them. CONCLUSION: Immune profiles of small HER2-positive breast cancers differ according to HR status, histological grade, and molecular subtype. Further work is needed to explore the implication of these findings on disease outcome. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00542451.
Authors
Barroso-Sousa, R; Barry, WT; Guo, H; Dillon, D; Tan, YB; Fuhrman, K; Osmani, W; Getz, A; Baltay, M; Dang, C; Yardley, D; Moy, B; Marcom, PK; Mittendorf, EA; Krop, IE; Winer, EP; Tolaney, SM
MLA Citation
Barroso-Sousa, R., et al. “The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial.Ann Oncol, vol. 30, no. 4, Apr. 2019, pp. 575–81. Pubmed, doi:10.1093/annonc/mdz047.
URI
https://scholars.duke.edu/individual/pub1428898
PMID
31987274
Source
pubmed
Published In
Ann Oncol
Volume
30
Published Date
Start Page
575
End Page
581
DOI
10.1093/annonc/mdz047

A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer.

BACKGROUND: Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination of capecitabine and ziv-aflibercept, and then we evaluated the efficacy of the combination in patients with chemotherapy refractory metastatic CRC. METHODS: All patients were required to have a Karnofsky Performance Status > 70% and adequate organ function. The phase Ib dose escalation cohort included patients with advanced solid tumors who had progressed on all standard therapies. Using a standard 3 + 3 design, we identified the MTD and RPTD for the combination. Fifty patients with metastatic CRC who had progressed on or were intolerant of a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab were then enrolled in a single-arm phase II expansion cohort, and were treated at the RPTD. Prior EGFR antibody therapy was required for subjects with RAS wildtype tumors. The primary endpoint for the expansion cohort was progression-free survival (PFS) at two months. Secondary endpoints included objective response rate (ORR) and overall survival (OS). RESULTS: A total of 63 patients were enrolled and evaluable for toxicity (13 dose escalation; 50 expansion). The MTD and RPTD were: capecitabine 850 mg/m2, P.O. bid, days 1-14, and ziv-aflibercept 6 mg/kg I.V., day 1, of each 21-day cycle. In the expansion cohort, 72% of patients were progression-free at two months (95% confidence interval [CI], 60-84%). Median PFS and OS were 3.9 months (95% CI, 2.3-4.5) and 7.1 months (95% CI: 5.8-10.0), respectively. Among all patients evaluable for toxicity, the most common treatment related adverse events (all grade [%]; grade ≥ 3 [%]) included palmar-plantar erythrodysesthesia (41%; 6%), hypertension (33%; 22%), and mucositis (19%; 5%). RNA was isolated from archived tumor specimens and gene expression analyses revealed no association between angiogenic biomarkers and clinical outcomes. CONCLUSION: The combination of capecitabine and ziv-aflibercept at the RPTD demonstrated acceptable safety and tolerability. PFS at 2 months in patients with chemotherapy refractory metastatic CRC was significantly greater than that in historical controls, indicating that this combination warrants further study. TRIAL REGISTRATION: This clinical trial was registered in the www.clinicaltrials.gov system as NCT01661972 on July 31, 2012.
Authors
Strickler, JH; Rushing, CN; Niedzwiecki, D; McLeod, A; Altomare, I; Uronis, HE; Hsu, SD; Zafar, SY; Morse, MA; Chang, DZ; Wells, JL; Blackwell, KL; Marcom, PK; Arrowood, C; Bolch, E; Haley, S; Rangwala, FA; Hatch, AJ; Nixon, AB; Hurwitz, HI
MLA Citation
Strickler, John H., et al. “A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer.Bmc Cancer, vol. 19, no. 1, Nov. 2019, p. 1032. Pubmed, doi:10.1186/s12885-019-6234-8.
URI
https://scholars.duke.edu/individual/pub1417915
PMID
31675952
Source
pubmed
Published In
Bmc Cancer
Volume
19
Published Date
Start Page
1032
DOI
10.1186/s12885-019-6234-8

Breast Cancer Version 2.2015.

Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This portion of the NCCN Guidelines discusses recommendations specific to the locoregional management of clinical stage I, II, and IIIA (T3N1M0) tumors.
Authors
Gradishar, WJ; Anderson, BO; Balassanian, R; Blair, SL; Burstein, HJ; Cyr, A; Elias, AD; Farrar, WB; Forero, A; Giordano, SH; Goetz, M; Goldstein, LJ; Hudis, CA; Isakoff, SJ; Marcom, PK; Mayer, IA; McCormick, B; Moran, M; Patel, SA; Pierce, LJ; Reed, EC; Salerno, KE; Schwartzberg, LS; Smith, KL; Smith, ML; Soliman, H; Somlo, G; Telli, M; Ward, JH; Shead, DA; Kumar, R
MLA Citation
Gradishar, William J., et al. “Breast Cancer Version 2.2015.J Natl Compr Canc Netw, vol. 13, no. 4, Apr. 2015, pp. 448–75. Pubmed, doi:10.6004/jnccn.2015.0060.
URI
https://scholars.duke.edu/individual/pub1063489
PMID
25870381
Source
pubmed
Published In
J Natl Compr Canc Netw
Volume
13
Published Date
Start Page
448
End Page
475
DOI
10.6004/jnccn.2015.0060