Gynecological Oncology CME ACCREDITED Watch Time: 31 mins

touchEXPERT OPINIONS Paving the way towards better patient outcomes in advanced or metastatic cervical cancer

Watch leading cervical cancer experts provide an update on the pathophysiology, biomarkers and emerging treatments for advanced or metastatic cervical cancer.

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Dr Marilyn Huang
Sylvester Comprehensive Cancer Center, Miami, FL, USA
How will biomarker testing improve outcomes in patients with advanced/metastatic cervical cancer?

Dr Marilyn Huang considers the use of biomarkers in the diagnosis, prognosis and treatment for cervical cancer. She presents an overview of how biomarkers are used in clinical practice, the data supporting their use and her view on the most promising emerging biomarkers.

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Interview Questions

In this interview, Dr Marilyn Huang answers the following questions:

  • What biomarkers are currently available and how do they inform the management of patients with cervical cancer?
  • How are biomarkers integrated with the use of immunotherapy for cervical cancer?
  • What are the most promising biomarkers under investigation?
  • How do you see emerging biomarkers being incorporated into clinical practice?
About Dr Marilyn Huang

Dr Huang is Associate Professor and Director of Translational Gynecologic Oncology Research at the University of Miami Miller School of Medicine and a gynecologic oncologist at the Sylvester Comprehensive Cancer Center, Miami, FL, USA. Dr Huang’s primary research goal is to enhance women’s health by bringing novel therapeutics and innovative drug combinations in clinical trial programs. She has been awarded multiple industry-sponsored, investigator-initiated grants evaluating new treatment options in gynaecologic malignancies, with a focus in immunotherapy. She is interested in exploring the tumour microenvironment in these patients to further clarify responders from potential non-responders, as well as assessing circulating biomarkers which correlate to therapeutic response.

Dr Marilyn Huang discloses: Grant support from Merck.

 
Dr Julius Strauss
Bethesda, MD, USA
How can we harness the tumour microenvironment for the benefit of patients with advanced/metastatic cervical cancer?

Dr Julius Strauss describes the key features of the tumour microenvironment, the oncogenic activity of human papillomavirus (HPV) and the mechanisms of immune escape, highlighting how different molecular targets can be exploited for therapeutic purposes.

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Interview Questions

In this interview, Dr Julius Strauss answers the following questions:

  • What is the tumour microenvironment and what are the key contributors to the development and progression of cervical cancer?
  • What is the role of HPV infection in the development and progression of cervical cancer?
  • How does HPV interact with the tumour microenvironment and the immune system leading to cancer progression and invasive disease?
  • How can the tumour microenvironment be targeted for therapeutic purposes in cervical cancer?
About Dr Julius Strauss

Dr Strauss received his medical degree from Stony Brook University Medical Center School of Medicine in 2010 and completed his internal medicine residency at Montefiore Medical Center in 2013. He joined the National Cancer Institute (NCI) Medical Oncology Service as a medical oncology fellow in 2013. Dr Strauss is the Co-Director of the Clinical Trials Group of the Laboratory of Tumor Immunology and Biology, NCI. He also has an adjunct appointment in the Genitourinary Malignancies Branch. He is board certified in medical oncology and internal medicine. Dr Strauss is part of the larger effort of the Laboratory of Tumor Immunology and Biology to create new immunotherapies for the treatment of cancer. Dr Strauss’s areas of expertise are immunotherapy, therapeutic cancer vaccines and immune checkpoint inhibitors.

Dr Julius Strauss discloses: Grant/research support to the National Institutes of Health (NIH) from EMD Serono Inc, Precigen and PDS Biotechnology for research on human papillomavirus (HPV)-associated malignancies. Dr Strauss is listed on a National Institutes of Health patent for the combined use of programmed death-ligand 1 (PD-L1) and transforming growth factor (TGF) beta blockade in HPV-associated malignancies.

 
Prof. Isabelle Ray-Coquard
Centre Leon Bérard, Lyon, France
Are we on the verge of a new horizon for patients with advanced/metastatic cervical cancer?

Prof. Isabelle Ray-Coquard outlines the current standard of care for patients with advanced, metastatic and recurrent cervical cancer. She presents the latest data on emerging immunotherapy options and antibody-drug conjugates.

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Interview Questions

In this interview, Prof. Isabelle Ray-Coquard answers the following questions:

  • What is the current standard of care for patients with advanced/metastatic and recurrent cervical cancer and what are the limitations of current treatments?
  • What does therapy with immune checkpoint inhibitors hold in the near future for the treatment of cervical cancer?
  • What is bintrafusp alfa and what outcomes have been reported to date in cervical cancer?
  • How does tisotumab vedotin work and what outcomes have been reported to date?
  • In your opinion, how will emerging agents and combinations be integrated into the current treatment paradigm for cervical cancer?
About Prof. Isabelle Ray-Coquard

Prof. Ray-Coquard obtained her medical degree in 1997, specializing in oncology. In 2003, she received her PhD from the Université Claude Bernard for her research on the factors that determine medical practices in oncology. She also received master’s degrees in statistics (in 1995) and medical economics (in 1996). From 2008 to 2013, she served as Chair of the gynaecologic group for clinical trials for the French National Cancer Institute (INCA), and she is currently the Network Director of the National Rare Ovarian Tumor Observatory (TMRO) (www.ovaire-rare.org), a network funded by the INCA commission and dedicated to the management of all rare gynaecological cancers. At the Groupe d’Investigateurs National Evaluation des Cancers de l’Ovaire (GINECO), she has been active in the translational research advisory committee, the scientific committee, and as a chairman of both the endometrial cancer subgroup and the rare tumours committee. Since 2002, she has been developing translational research dedicated to ovarian cancer with the Institut national de la santé et de la recherche médicale (INSERM) within the Centre de Recherche en Cancérologie de Lyon (CRCL), directed by Prof. Alain Puisieux within the Léon Bérard Comprehensive Cancer Centre (CLB) campus, and more directly with the Research Team 11 of CRCL. From 2009 to 2016, she was the Chair of the Rare Cancer Working Group from the Gynecologic Cancer InterGroup (GCIG), dedicated to clinical trials in the field of all gynaecological cancers. She is the current President of the GINECO group. read more

She is an active member of a number of professional groups, including the American Society of Clinical Oncology (ASCO), the American Association for Cancer Research (AACR), the Connective Tissue Oncology Society (CTOS), the French Society of Cancer (SFCO), the European Association of Cancer Research (EACR), the European Organisation for Research and Treatment of Cancer (EORTC) , the European Society of Medical Oncology (ESMO) and the European Society of Gynaecological Oncology (ESGO).

Prof. Isabelle Ray-Coquard discloses: Consultant/Advisory Boards for AstraZeneca, Clovis Oncology, MSD, Bristol Myers Squibb and GlaxoSmithKline.

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Overview & Learning Objectives
Overview

In this activity, experts in cervical cancer consider the place for biomarkers, the role of the tumour microenvironment in disease development and progression, and emerging treatment options for advanced or metastatic cervical cancer.

This activity has been jointly provided by Oakstone and touchIME ONCOLOGY. Oakstone Publishing is accredited by the ACCME to provide continuing medical education to physicians. read more

Target audience

This activity has been designed to meet the educational needs of gynaecological oncologists, oncologists and oncology nurses.

Disclosures

Oakstone Publishing has assessed conflict of interest with its faculty, authors, editors, and any individuals who were in a position to control the content of this CME activity. Any identified relevant conflicts of interest were resolved for fair balance and scientific objectivity of studies utilized in this activity. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relevant commercial interests.

Faculty

Dr Marilyn Huang discloses: Grant support from Merck.

Dr Julius Strauss discloses: Grant/research support to the National Institutes of Health (NIH) from EMD Serono Inc, Precigen and PDS Biotechnology for research on human papillomavirus (HPV)-associated malignancies. Dr Strauss is listed on a National Institutes of Health patent for the combined use of programmed death-ligand 1 (PD-L1) and transforming growth factor (TGF) beta blockade in HPV-associated malignancies.

Prof. Isabelle Ray-Coquard discloses: Consultant/Advisory Boards for AstraZeneca, Clovis Oncology, MSD, Bristol Myers Squibb and GlaxoSmithKline.

Content Reviewer

Walter Murray Yarbrough, MD, has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Hannah Fisher has no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™️. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In order to receive credit for this activity, participants must review and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AME). European physicians interested in converting AMA PRA Category 1 Credit™ into European CME credit (ECMEC) should contact the UEMS (www.uems.eu)

Date of original release: 10 December 2020. Date credits expire: 10 December 2021.

Learning Objectives

After watching this activity, you should be able to:

  • Recognize the importance of biomarker testing in the screening and monitoring of cervical cancer
  • Discuss the role of the tumour microenvironment in the development and progression of invasive cervical cancer
  • Interpret the most recent data for new potential therapies for advanced or recurrent cervical cancer
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Question 1/4
Which of the following biomarkers is used as the best predictor of the risk of developing cervical cancer together with cytologic screening tests?

CEA, carcinoembryonic antigen; HPV, human papillomavirus; PD-L1, programmed death-ligand-1; SCC-Ag, squamous cell carcinoma antigen.
Correct

Persistent HPV infection is a major risk factor for the development of cervical cancer and high-risk HPV types are detected in the vast majority of cervical cancer cases.1 SSC-Ag and CEA have shown promise as potential prognostic markers for cervical cancer, but they are not widely used.2,3 PD-L1 expression on tumour cells is used to determine the suitability of patients for anti-PD-1/PD-L1 therapy.4

References

  1. Pal A, Kundu R. Front Microbiol. 2020;10:3116.
  2. Laengsri V, et al. Lab Med. 2018;49:97–111.
  3. Huang G, et al. Onco Targets Ther. 2020;13:5155–64.
  4. Chung HC, et al. J Clin Oncol. 2019;37:1470–8.
Question 2/4
How do the E6 and E7 proteins allow HPV to evade immune recognition?

HPV, human papillomavirus; IFN, interferon; TGF-β, transforming growth factor beta.
Correct

To establish a persistent infection, HPV employs several mechanisms that disrupt STAT (signal transducer and activator of transcription) 1/2 signalling and thereby inhibit the expression of interferon-stimulated genes. E6 and E7 reduce STAT1 protein expression and the E6 protein of the high-risk HPV type 18 directly binds to molecules involved in IFN signalling, thus preventing the downstream expression of IFN-stimulated genes.1

The oncoproteins E6 and E7 of high-risk HPV types also impair immune response by promoting the production of TGF-β by increasing the activity of the TGF-β promoter. TGF-β may induce local immune suppression that impairs immune surveillance and therefore contributes to increased susceptibility to malignant transformation.2

References

  1. Morgan EL, Macdonald A. Viruses. 2020;12:E977.
  2. Wakabayashi R, et al. Microorganisms. 2019;7:199.
Question 3/4
Your patient is a 51-year-old female who has been diagnosed with stage IVB cervical cancer with bone and lung metastases. She has an ECOG performance status of 1. Which of the following treatment options would you consider for first-line therapy?

ECOG, Eastern Cooperative Oncology Group.
Correct

NCCN (National Comprehensive Cancer Network) guidelines recommend combination chemotherapy (carboplatin/paclitaxel and cisplatin/paclitaxel) with bevacizumab as the preferred first-line treatment for metastatic cervical cancer.1

ESGO (European Society of Gynaecologic Oncology) guidelines recommend combination chemotherapy (carboplatin/paclitaxel and cisplatin/paclitaxel) as the preferred first-line treatment for widespread distant metastatic disease at presentation, with the addition of bevacizumab in patients with good performance status.2

References

  1. NCCN Clinical Practice Guidelines in Oncology, Cervical Cancer, Version 1.2021 — October 2, 2020. Available at: www.nccn.org/professionals/physician_gls/pdf/cervical.pdf (accessed 22 October 2020).
  2. Cibula D, et al. Int J Gynecol Cancer. 2018;28:641–55.
Question 4/4
Based on early clinical trials, in what range is the objective response rate achieved in patients with cervical cancer treated with tisotumab vedotin or bintrufasp alfa?
Correct

Tisotumab vedotin is an antibody-drug conjugate consisting of three TF-binding sites conjugated with the tubulin inhibitor MMAE.1 The innovaTV 201 (phase I/II, NCT02001623) and innovaTV 204 (phase II, NCT03438396) trials tested tisotumab vedotin at 2 mg/kg every 3 weeks in patients with relapsed, advanced or metastatic cervical cancer.1,2 The IRC-assessed ORRs in these trials were 22% and 24%, respectively.1,2
Bintrafusp alfa is a bifunctional fusion protein that blocks both PD-L1 and TGF-β.3,4 In a phase I trial of patients with pre-treated advanced solid tumours (NCT02517398), analysis of patients with cervical cancer showed an ORR of 24%.5

IRC, independent review committee; MMAE, monomethyl auristatin E; ORR, objective response rate; PFS, progression-free survival; TF, tissue factor.

References

  1. Hong DS, et al. Clin Cancer Res. 2020;26:1220–8.
  2. Coleman RL, et al. Ann Oncol. 2020;31(Suppl. 4):S1142–215.
  3. Strauss J, et al. Clin Cancer Res. 2018;24:1287–95.
  4. Cho BC, et al. J Immunother Cancer. 2020;8:1–9.
  5. Allan S, et al. Int J Gyn Canc. 2019;29:A72–3.
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