Michael Harrison

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2004

Tulane University

residency, Medicine

Tulane University

Grants:

Bladder Cancer in Older Adults - Treatment and Outcomes

Administered By
Duke Clinical Research Institute
Awarded By
AstraZeneca Pharmaceuticals, LP
Role
Co Investigator
Start Date
End Date

ATLAS: A Phase 2, Open-label Study of Rucaparib in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

Administered By
Duke Cancer Institute
Awarded By
Clovis Oncology, Inc.
Role
Principal Investigator
Start Date
End Date

STUDY/PROTOCOL TITLE AND PROTOCOL NUMBER: "A Phase II, Open-label Randomized Study of Immediate Prostatectomy vs. Cabozantinib Followed by Prostatectomy in Men with High Risk Prostate Cancer"; XL184-IST64

Administered By
Duke Cancer Institute
Awarded By
Exelixis, Inc
Role
Principal Investigator
Start Date
End Date

A Phase 3, Open-label, Randomized Study of Nivolumab Combined with Ipilimumab, or with Standard of Care Chemotherapy, versus Standard of Care Chemotherapy in Participants with Previously Untreated Unr

Administered By
Duke Cancer Institute
Awarded By
Bristol-Myers Squibb Company
Role
Principal Investigator
Start Date
End Date

Phase II Single Arm Study of Gemcitabine and Cisplatin plus Pembrolizumab as Neoadjuvant Therapy Prior to Radical Cystectomy in Patients with Muscle-Invasive Bladder Cancer

Administered By
Duke Cancer Institute
Awarded By
University of North Carolina - Chapel Hill
Role
Principal Investigator
Start Date
End Date

Publications:

Referral and adjuvant treatment patterns after nephrectomy in high-risk locoregional renal cell carcinoma.

BACKGROUND: It is unclear whether patients with renal cell carcinoma (RCC) are routinely assessed for recurrence risk post-nephrectomy and whether patients at high recurrence risk are seen by providers who can evaluate candidacy for adjuvant systemic therapy (AST) and clinical trials. MATERIALS AND METHODS: We identified all patients with locoregional RCC who underwent nephrectomy via an institutional database within Duke University Health System between 1 April 2015 and 31 December 2019. Medical records were reviewed to identify patient characteristics, post-nephrectomy referrals, treatment, and follow-up. Patients with tumor stage ≥3 and grade ≥2, regional lymph node metastasis, or both, were classified as high recurrence risk. RESULTS: Of 618 patients with locoregional RCC who underwent nephrectomy, 136 (22%) had high recurrence risk. Of those, 25 patients with high-risk disease (18%) were referred to medical oncology for discussion of AST; 23 (92%) of these referrals took place in 2018-2019. One patient received adjuvant sunitinib and two patients participated in adjuvant immunotherapy trials. The decision not to receive AST was primarily made by the oncologist in 10 (46%), the patient in 8 (36%), and unrecorded in 4 (18%) of 22 cases, for multiple reasons. Individual surgeons referred high-risk patients for discussion of AST with varying frequency, ranging from 0% to 100% in 2019. CONCLUSIONS: Despite increasing number of patients with locoregional RCC at high recurrence risk referred to medical oncologists after nephrectomy, few patients received AST, including participation in clinical trials. With increasing AST options and ongoing clinical trials in this space, these findings highlight the need for continued efforts at identifying effective AST and referring patients most likely to benefit to medical oncologists. ClinicalTrials.gov, NCT04309617.
Authors
Dzimitrowicz, H; Esterberg, E; Miles, L; Zanotti, G; Borham, A; Harrison, MR
MLA Citation
Dzimitrowicz, Hannah, et al. “Referral and adjuvant treatment patterns after nephrectomy in high-risk locoregional renal cell carcinoma.Cancer Med, Nov. 2021. Pubmed, doi:10.1002/cam4.4407.
URI
https://scholars.duke.edu/individual/pub1500920
PMID
34751002
Source
pubmed
Published In
Cancer Medicine
Published Date
DOI
10.1002/cam4.4407

Clinical Activity and Safety of Cabozantinib for Brain Metastases in Patients With Renal Cell Carcinoma.

Patients with brain metastases from renal cell carcinoma (RCC) have been underrepresented in clinical trials, and effective systemic therapy is lacking. Cabozantinib shows robust clinical activity in metastatic RCC, but its effect on brain metastases remains unclear. To assess the clinical activity and toxic effects of cabozantinib to treat brain metastases in patients with metastatic RCC. This retrospective cohort study included patients with metastatic RCC and brain metastases treated in 15 international institutions (US, Belgium, France, and Spain) between January 2014 and October 2020. Cohort A comprised patients with progressing brain metastases without concomitant brain-directed local therapy, and cohort B comprised patients with stable or progressing brain metastases concomitantly treated by brain-directed local therapy. Receipt of cabozantinib monotherapy at any line of treatment. Intracranial radiological response rate by modified Response Evaluation Criteria in Solid Tumors, version 1.1, and toxic effects of cabozantinib. Of the 88 patients with brain metastases from RCC included in the study, 33 (38%) were in cohort A and 55 (62%) were in cohort B; the majority of patients were men (n = 69; 78%), and the median age at cabozantinib initiation was 61 years (range, 34-81 years). Median follow-up was 17 months (range, 2-74 months). The intracranial response rate was 55% (95% CI, 36%-73%) and 47% (95% CI, 33%-61%) in cohorts A and B, respectively. In cohort A, the extracranial response rate was 48% (95% CI, 31%-66%), median time to treatment failure was 8.9 months (95% CI, 5.9-12.3 months), and median overall survival was 15 months (95% CI, 9.0-30.0 months). In cohort B, the extracranial response rate was 38% (95% CI, 25%-52%), time to treatment failure was 9.7 months (95% CI, 6.0-13.2 months), and median overall survival was 16 months (95% CI, 12.0-21.9 months). Cabozantinib was well tolerated, with no unexpected toxic effects or neurological adverse events reported. No treatment-related deaths were observed. In this cohort study, cabozantinib showed considerable intracranial activity and an acceptable safety profile in patients with RCC and brain metastases. Support of prospective studies evaluating the efficacy of cabozantinib for brain metastases in patients with RCC is critical.
Authors
Hirsch, L; Martinez Chanza, N; Farah, S; Xie, W; Flippot, R; Braun, DA; Rathi, N; Thouvenin, J; Collier, KA; Seront, E; de Velasco, G; Dzimitrowicz, H; Beuselinck, B; Xu, W; Bowman, IA; Lam, ET; Abuqayas, B; Bilen, MA; Varkaris, A; Zakharia, Y; Harrison, MR; Mortazavi, A; Barthélémy, P; Agarwal, N; McKay, RR; Brastianos, PK; Krajewski, KM; Albigès, L; Harshman, LC; Choueiri, TK
MLA Citation
Hirsch, Laure, et al. “Clinical Activity and Safety of Cabozantinib for Brain Metastases in Patients With Renal Cell Carcinoma.Jama Oncology, Oct. 2021. Epmc, doi:10.1001/jamaoncol.2021.4544.
URI
https://scholars.duke.edu/individual/pub1499425
PMID
34673916
Source
epmc
Published In
Jama Oncology
Published Date
DOI
10.1001/jamaoncol.2021.4544

Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer.

PURPOSE: To evaluate the safety and efficacy of gemcitabine and cisplatin in combination with the immune checkpoint inhibitor pembrolizumab as neoadjuvant therapy before radical cystectomy (RC) in muscle-invasive bladder cancer. METHODS: Patients with clinical T2-4aN0/XM0 muscle-invasive bladder cancer eligible for RC were enrolled. The initial six patients received lead-in pembrolizumab 200 mg once 2 weeks prior to pembrolizumab 200 mg once on day 1, cisplatin 70 mg/m2 once on day 1, and gemcitabine 1,000 mg/m2 once on days 1 and 8 every 21 days for four cycles. This schedule was discontinued for toxicity and subsequent patients received cisplatin 35 mg/m2 once on days 1 and 8 without lead-in pembrolizumab. The primary end point was pathologic downstaging (< pT2N0) with null and alternative hypothesis rates of 35% and 55%, respectively. Secondary end points were toxicity including patient-reported outcomes, complete pathologic response (pT0N0), event-free survival, and overall survival. Association of pathologic downstaging with programmed cell death ligand 1 staining was explored. RESULTS: Thirty-nine patients were enrolled between June 2016 and March 2020 (72% cT2, 23% cT3, and 5% cT4a). Patients received a median of four cycles of therapy. All patients underwent RC except one who declined. Twenty-two of 39 patients (56% [95% CI, 40 to 72]) achieved < pT2N0 and 14 of 39 (36% [95% CI, 21 to 53]) achieved pT0N0. Most common adverse events (AEs) of any grade were thrombocytopenia (74%), anemia (69%), neutropenia (67%), and hypomagnesemia (67%). One patient had new-onset type 1 diabetes mellitus with ketoacidosis related to pembrolizumab and no patients required steroids for immune-related AEs. Clinicians consistently under-reported AEs when compared with patients. CONCLUSION: Neoadjuvant gemcitabine and cisplatin plus pembrolizumab met its primary end point for improved pathologic downstaging and was generally safe. A global study of perioperative chemotherapy plus pembrolizumab or placebo is ongoing.
Authors
Rose, TL; Harrison, MR; Deal, AM; Ramalingam, S; Whang, YE; Brower, B; Dunn, M; Osterman, CK; Heiling, HM; Bjurlin, MA; Smith, AB; Nielsen, ME; Tan, H-J; Wallen, E; Woods, ME; George, D; Zhang, T; Drier, A; Kim, WY; Milowsky, MI
MLA Citation
Rose, Tracy L., et al. “Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer.J Clin Oncol, vol. 39, no. 28, Oct. 2021, pp. 3140–48. Pubmed, doi:10.1200/JCO.21.01003.
URI
https://scholars.duke.edu/individual/pub1494307
PMID
34428076
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
39
Published Date
Start Page
3140
End Page
3148
DOI
10.1200/JCO.21.01003

A Prospective Multicenter Evaluation of Initial Treatment Choice in Metastatic Renal Cell Carcinoma Prior to the Immunotherapy Era: The MaRCC Registry Experience.

INTRODUCTION: The Metastatic Renal Cell Carcinoma (MaRCC) Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC). METHODS AND MATERIALS: Patients with mRCC and no prior systemic therapy were enrolled at academic and community sites. End of study data collection was in March 2019. Outcomes included overall survival (OS). A survey of treating physicians assessed reasons for treatment initiations and discontinuations. RESULTS: Overall, 376 patients with mRCC initiated first-line therapy; 171 (45.5%) received pazopanib, 75 (19.9%) sunitinib, and 74 (19.7%) participated in a clinical trial. Median (95% confidence interval) OS was longest in the clinical trial group (50.3 [35.8-not reached] months) versus pazopanib (39.0 [29.7-50.9] months) and sunitinib 26.2 [19.9-61.5] months). Non-clear cell RCC (21.5% of patients) was associated with worse median OS than clear cell RCC (18.0 vs. 47.3 months). Differences in baseline characteristics, treatment starting dose, and relative dose exposure among treatment groups suggest selection bias. Survey results revealed a de-emphasis on quality of life, toxicity, and patient preference compared with efficacy in treatment selection. CONCLUSION: The MaRCC Registry gives insights into real-world first-line treatment selection, outcomes, and physician rationale regarding initial treatment selection prior to the immunotherapy era. Differences in outcomes between clinical trial and off-study patients reflect the difficulty in translating trial results to real-world patients, and emphasize the need to broaden clinical trial eligibility. Physician emphasis on efficacy over quality of life and toxicity suggests more data and education are needed regarding these endpoints.
Authors
Costello, BA; Bhavsar, NA; Zakharia, Y; Pal, SK; Vaishampayan, U; Jim, H; Fishman, MN; Molina, AM; Kyriakopoulos, CE; Tsao, C-K; Appleman, LJ; Gartrell, BA; Hussain, A; Stadler, WM; Agarwal, N; Pachynski, RK; Hutson, TE; Hammers, HJ; Ryan, CW; Mardekian, J; Borham, A; George, DJ; Harrison, MR
MLA Citation
Costello, Brian A., et al. “A Prospective Multicenter Evaluation of Initial Treatment Choice in Metastatic Renal Cell Carcinoma Prior to the Immunotherapy Era: The MaRCC Registry Experience.Clin Genitourin Cancer, July 2021. Pubmed, doi:10.1016/j.clgc.2021.07.002.
URI
https://scholars.duke.edu/individual/pub1493276
PMID
34364796
Source
pubmed
Published In
Clin Genitourin Cancer
Published Date
DOI
10.1016/j.clgc.2021.07.002

Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Locally advanced or metastatic urothelial carcinoma is generally incurable and has scarce treatment options, especially for cisplatin-ineligible patients previously treated with PD-1 or PD-L1 therapy. Enfortumab vedotin is an antibody-drug conjugate directed at Nectin-4, a protein highly expressed in urothelial carcinoma. We aimed to evaluate the efficacy and safety of enfortumab vedotin in the post-immunotherapy setting in cisplatin-ineligible patients. METHODS: EV-201 is a multicentre, single-arm, phase 2 study of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma previously treated with PD-1 or PD-L1 inhibitors. Cohort 2 included adults (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status score of 2 or less who were considered ineligible for cisplatin at enrolment and who had not received platinum-containing chemotherapy in the locally advanced or metastatic setting. Enfortumab vedotin was given intravenously at a dose of 1·25 mg/kg on days 1, 8, and 15 of every 28-day cycle. The primary endpoint was confirmed objective response rate per Response Evaluation Criteria in Solid Tumours version 1.1 assessed by blinded independent central review. Efficacy and safety were analysed in all patients who received at least one dose of enfortumab vedotin. EV-201 is an ongoing study and the primary analysis is complete. This study is registered with Clinicaltrials.gov, NCT03219333. FINDINGS: Between Oct 8, 2017, and Feb 11, 2020, 91 patients were enrolled at 40 sites globally, of whom 89 received treatment. Median follow-up was 13·4 months (IQR 11·3-18·9). At data cutoff (Sept 8, 2020), the confirmed objective response rate was 52% (46 of 89 patients; 95% CI 41-62), with 18 (20%) of 89 patients achieving a complete response and 28 (31%) achieving a partial response. 49 (55%) of 89 patients had grade 3 or worse treatment-related adverse events. The most common grade 3 or 4 treatment-related adverse events were neutropenia (eight [9%] patients), maculopapular rash (seven [8%] patients), and fatigue (six [7%] patients). Treatment-related serious adverse events occurred in 15 (17%) patients. Three (3%) patients died due to acute kidney injury, metabolic acidosis, and multiple organ dysfunction syndrome (one [1%] each) within 30 days of first dose and these deaths were considered by the investigator to be related to treatment; a fourth death from pneumonitis occurred more than 30 days after the last dose and was also considered to be related to treatment. INTERPRETATION: Treatment with enfortumab vedotin was tolerable and confirmed responses were seen in 52% of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma who were previously treated with PD-1 or PD-L1 inhibitors. These patients have few treatment options, and enfortumab vedotin could be a promising new therapy for a patient population with a high unmet need. FUNDING: Astellas Pharma Global Development and Seagen.
Authors
Yu, EY; Petrylak, DP; O'Donnell, PH; Lee, J-L; van der Heijden, MS; Loriot, Y; Stein, MN; Necchi, A; Kojima, T; Harrison, MR; Hoon Park, S; Quinn, DI; Heath, EI; Rosenberg, JE; Steinberg, J; Liang, S-Y; Trowbridge, J; Campbell, M; McGregor, B; Balar, AV
MLA Citation
Yu, Evan Y., et al. “Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial.Lancet Oncol, vol. 22, no. 6, June 2021, pp. 872–82. Pubmed, doi:10.1016/S1470-2045(21)00094-2.
URI
https://scholars.duke.edu/individual/pub1483071
PMID
33991512
Source
pubmed
Published In
Lancet Oncol
Volume
22
Published Date
Start Page
872
End Page
882
DOI
10.1016/S1470-2045(21)00094-2