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Lung Cancer, Immunotherapy CE/CME ACCREDITED Watch Time: 48 mins

touchMDT Uncharted territory: Introducing novel immunotherapeutic approaches for metastatic NSCLC without driver mutations

Leading specialists and a patient advocate discuss novel immunotherapies for non-driver mutation metastatic non-small cell lung cancer (NSCLC).

 Overview & Learning Objectives

Patient with non-driver mutation metastatic NSCLC

Medical Oncologist, Oncology Pharmacist and Pathologist
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Limits of immunotherapy for metastatic NSCLC Prof. Raffaele Califano, Prof. Lisa Holle, Prof. Albrecht Stenzinger

Watch a medical oncologist, an oncology pharmacist and a pathologist discuss the limitations of standard-of-care immunotherapy for the treatment of non-driver mutation metastatic NSCLC.

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Pathologist and Medical Oncologist
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Predictive biomarkers for immunotherapy Prof. Albrecht Stenzinger, Prof. Raffaele Califano

Watch a pathologist and a medical oncologist discuss prognostic and predictive biomarkers for immunotherapy.

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Oncology Pharmacist and Medical Oncologist
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Overcoming resistance to immunotherapy Prof. Lisa Holle, Prof. Raffaele Califano

Watch an oncology pharmacist and a medical oncologist review novel strategies to overcome resistance to standard-of-care immunotherapy for non-driver mutation metastatic NSCLC.

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Medical Oncologist, Oncology Pharmacist and Patient Advocate
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Medical Oncologist, Oncology Pharmacist and Patient Advocate Prof. Raffaele Califano, Prof. Lisa Holle, Mr Josh Colow

Watch a medical oncologist, an oncology pharmacist and a survivor of metastatic NSCLC discuss shared decision making and the importance of including patient preference in treatment decisions.

Watch Video
Medical Oncologist, Oncology Pharmacist and Pathologist

Watch a medical oncologist, an oncology pharmacist and a pathologist discuss the limitations of standard-of-care immunotherapy for the treatment of non-driver mutation metastatic NSCLC.
Expert Spotlight
Prof. Raffaele Califano
The Christie and Manchester University Hospital, Manchester, UK
Prof. Lisa Holle
University of Connecticut School of Medicine, Storrs, and UConn Health: Neag Comprehensive Cancer Center, Farmington, CT, USA
Prof. Albrecht Stenzinger
University Hospital Heidelberg, Heidelberg, Germany

Prof. Raffaele Califano, Prof. Lisa Holle and Prof. Albrecht Stenzinger discuss the challenges associated with standard-of-care immunotherapy for metastatic NSCLC without driver mutations, including treatment resistance and toxicity.

Listen on the Go

 Learn More Back to MDT Hub Time: 11:34
 
Pathologist and Medical Oncologist

Watch a pathologist and a medical oncologist discuss prognostic and predictive biomarkers for immunotherapy.
Expert Spotlight
Prof. Albrecht Stenzinger
University Hospital Heidelberg, Heidelberg, Germany
Prof. Raffaele Califano
The Christie and Manchester University Hospital, Manchester, UK

Prof. Albrecht Stenzinger and Prof. Raffaele Califano discuss the tools used to predict response to immunotherapy, and they review emerging biomarkers.

Listen on the Go

 Learn More Back to MDT Hub Time: 11:55
 
Oncology Pharmacist and Medical Oncologist

Watch an oncology pharmacist and a medical oncologist review novel strategies to overcome resistance to standard-of-care immunotherapy for non-driver mutation metastatic NSCLC.
Expert Spotlight
Prof. Lisa Holle
University of Connecticut School of Medicine, Storrs, and UConn Health: Neag Comprehensive Cancer Center, Farmington, CT, USA
Prof. Raffaele Califano
The Christie and Manchester University Hospital, Manchester, UK

Prof. Lisa Holle and Prof. Raffaele Califano review novel approaches to overcome resistance to standard-of-care immunotherapy for non-driver mutation metastatic NSCLC, including new immune checkpoint inhibitor combinations and emerging novel targets.

Listen on the Go

 Learn More Back to MDT Hub Time: 12:07
 
Medical Oncologist, Oncology Pharmacist and Patient Advocate

Watch a medical oncologist, an oncology pharmacist and a survivor of metastatic NSCLC discuss shared decision making and the importance of including patient preference in treatment decisions.
Expert Spotlight
Prof. Raffaele Califano
The Christie and Manchester University Hospital, Manchester, UK
Prof. Lisa Holle
University of Connecticut School of Medicine, Storrs, and UConn Health: Neag Comprehensive Cancer Center, Farmington, CT, USA
Mr Josh Colow
Woodstock, NY, USA

Prof. Raffaele Califano and Prof. Lisa Holle are joined by Mr Josh Colow, a survivor of metastatic NSCLC. Together, they discuss the importance of involving patients in their treatment decisions and how clinicians can best support patients throughout their treatment journey.

Listen on the Go

 Learn More Back to MDT Hub Time: 12:07
 
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Overview & Learning Objectives
Overview

Watch multidisciplinary experts and a patient advocate discuss novel immunotherapeutic options for patients with non-driver mutation metastatic NSCLC, and how to best support patients throughout their treatment journey.

This activity is jointly provided by USF Health and touchIME.

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Target Audience

This activity has been designed to meet the educational needs of specialists involved in the management of non-driver mutation metastatic NSCLC, including academic and community medical oncologists, pathologists, oncology pharmacists and advanced practice providers.

Disclosures

USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity. The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Prof. Raffaele Califano discloses: Advisory board or panel fees, consultancy fees, and speaker’s bureau fees from AstraZeneca, Bayer, Boeringher Ingelheim, Bristol Myers Squibb, Janssen, Lilly Oncology, MSD, Novartis, Pfizer, Roche, Sanofi and Takeda. Grants/research support from Abbvie, AstraZeneca, Bristol Myers Squibb, Clovis, Janssen, Lilly Oncology, MSD, Novartis, Pfizer, Roche and Takeda. Stock/shareholder (self-managed) from Leaders in Oncology.

Prof. Lisa Holle has no interests/relationships or affiliations to disclose in relation to this activity.

Prof. Albrecht Stenzinger discloses: Advisory board or panel fees, and speaker’s bureau fees from AGCT, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, Illumina, Janssen, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda and Thermo Fisher. Grants/research support from Bayer, Bristol Myers Squibb, Chugai and Incyte.

Mr Josh Colow has no interests/relationships or affiliations to disclose in relation to this activity.

Content reviewer

Angela Hill, PharmD, CRPh has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Katrina Lester has no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

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

If you have questions regarding credit please contact cpdsupport@usf.edu 

Accreditations

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 1.0 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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 (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Advanced Practice Providers

Physician Assistants may claim a maximum of 1.0 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Pharmacists

USF Health is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This knowledge-based program has been approved for 1.0 contact hours (1.0 CEUs).  Universal program number is as follows: 0230-9999-23-005-H01-P.

Date of original release: 27 March 2023. Date credits expire: 27 March 2024.

If you have any questions regarding credit please contact cpdsupport@usf.edu

Learning Objectives

After watching this activity, participants should be better able to:

  • Outline the determinants of response and resistance to immune checkpoint blockade in patients with non-driver mutation metastatic NSCLC
  • Discuss the mechanisms of action and latest data for novel immunotherapy regimens in the management of non-driver mutation metastatic NSCLC
  • Appraise strategies for involving patients with non-driver mutation metastatic NSCLC in their healthcare for optimal outcomes
Faculty & Disclosures
Prof. Raffaele Califano

The Christie and Manchester University Hospital, Manchester, UK

Prof. Raffaele Califano is a consultant medical oncologist at The Christie Hospital in Manchester, UK. He is also a professor of medical oncology and honorary clinical chair of the Manchester Academic Health Science Centre at the University of Manchester.

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Prof. Califano’s interests lie in thoracic malignancies and clinical cancer research, and he is the clinical trials lead for the lung team at The Christie Hospital. Prof. Califano has been an investigator on several clinical trials, including immunotherapies for advanced NSCLC, small cell lung cancer and mesothelioma.

Prof. Califano is a member of the European Society for Medical Oncology Publishing Working Group, the European Organisation for Research and Treatment of Cancer Lung Cancer Group, the British Thoracic Oncology Group and International Association for the Study of Lung Cancer.

Prof. Raffaele Califano discloses: Advisory board or panel fees, consultancy fees, and speaker’s bureau fees from AstraZeneca, Bayer, Boeringher Ingelheim, Bristol Myers Squibb, Janssen, Lilly Oncology, MSD, Novartis, Pfizer, Roche, Sanofi and Takeda. Grants/research support from Abbvie, AstraZeneca, Bristol Myers Squibb, Clovis, Janssen, Lilly Oncology, MSD, Novartis, Pfizer, Roche and Takeda. Stock/shareholder (self-managed) from Leaders in Oncology
Prof. Lisa Holle

University of Connecticut School of Medicine, Storrs, and UConn Health: Neag Comprehensive Cancer Center, Farmington, CT, USA

Prof. Lisa Holle is a clinical professor at the University of Connecticut (UConn) School of Pharmacy and the UConn School of Medicine, CT, USA. Her practice site is at the UConn Health: Neag Comprehensive Cancer Center, where she works in a team-based ambulatory care clinic.

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Prof. Holle has worked as an oncology pharmacist for over 20 years in a variety of settings, including private hospitals, academic medical centres and medical communications. Her clinical research programme focuses on numeracy and patient decision making, oncology quality improvement initiatives, medical marijuana and oral anticancer therapy management.

Prof. Holle is a past president of the Hematology Oncology Pharmacy Association and a past secretariat member and past treasurer of the International Society of Oncology Pharmacy Practitioners. She is also an active member in many other professional oncology and pharmacy organizations.

Prof. Lisa Holle has no interests/relationships or affiliations to disclose in relation to this activity.
Prof. Albrecht Stenzinger

University Hospital Heidelberg, Heidelberg, Germany

Prof. Albrecht Stenzinger is professor of molecular tumour pathology and deputy director of the Institute of Pathology (IPH), as well as the head of the IPH Center for Molecular Pathology and section head for Molecular Diagnostics and Biomarker Development at the IPH, University Hospital Heidelberg, Germany.

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Prof. Stenzinger is a board-certified surgical pathologist and senior attending physician. He has broad expertise in molecular pathology and works in the field of translational research and genetics of solid tumours, including lung cancer.

Prof. Albrecht Stenzinger discloses: Advisory board or panel fees, and speaker’s bureau fees from AGCT, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, Illumina, Janssen, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda and Thermo Fisher. Grants/research support from Bayer, Bristol Myers Squibb, Chugai and Incyte.
Mr Josh Colow

Woodstock, NY, USA

Mr Josh Colow was born in New York City and raised in Woodstock, NY, USA. Josh was diagnosed with stage IV NSCLC non-small cell lung cancer (adenocarcinoma) in July 2018. He belongs to many online lung cancer support groups through which he helps himself and others gain hope and knowledge, and receive the emotional support a lung cancer survivor needs. Josh continues to work as a musician, which has been the focus of his career to date.

Mr Josh Colow has no interests/relationships or affiliations to disclose in relation to this activity.
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This Activity Is Funded By:

An independent medical education grant from AstraZeneca.
This activity is jointly provided by USF Health and touchIME.

The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

This content is intended for healthcare professionals.

Date of original release: 27 March 2023. Date credits expire: 27 March 2024.

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Question 1/5
Which of the following prognostic markers has demonstrated promising potential as a predictor of response to ICI monotherapy in patients with advanced or metastatic NSCLC without driver mutations?

ICI, immune checkpoint inhibitor; IFN-β, interferon-beta; IL-14, interleukin 14; LIPI, lung immune prognostic index; NSCLC, non-small cell lung cancer.
Correct

The LIPI score is an inflammation-related prognostic model based on dNLR ≥3 and LDH ≥2.5 x ULN.1 Studies have shown an association between a high LIPI score and poor outcomes in patients with lung cancer treated with immunotherapy,1 chemotherapy and targeted therapy.2

Abbreviations

dNLR, derived neutrophil-to-lymphocyte ratio; LDH, lactate dehydrogenase; LIPI, lung immune prognostic index; ULN, upper limit of normal.

References

  1. Mezquita L, et al. JAMA Oncol. 2018;4:351–7.
  2. Huang L, et al. Front Oncol. 2021;11:670230.
Question 2/5
How would you best counsel your patient with non-driver mutation metastatic NSCLC who needs to discontinue first-line pembrolizumab + CT after 18 months’ treatment due to a grade 4 irAE?

CT, chemotherapy; irAE, immune-related adverse event; NSCLC, non-small cell lung cancer.
 Correct

According to the FDA and EMA, pembrolizumab should be permanently discontinued following development of grade 4 irAEs; there are no recommended dose reductions.1,2 Evidence from retrospective studies has shown that discontinuation of ICIs (pembrolizumab, nivolumab and atezolizumab) in patients treated for >6 months without disease progression was associated with a durable response after ICI discontinuation, regardless of the cause of discontinuation.3–5

Abbreviations

EMA, European Medicines Agency; FDA, US Food and Drug Administration; ICI, immune checkpoint inhibitor; irAE, immune-related adverse event.

References

  1. FDA. Pembrolizumab PI. Available at: bit.ly/3IHa5NL (accessed 8 March 2023).
  2. EMA. Pembrolizumab SmPC. Available at: bit.ly/3YidGaN (accessed 8 March 2023).
  3. Kim H, et al. Cancer. 2022;128:778–87.
  4. Tachihara M, et al. BMC Cancer. 2018;18:946.
  5. Kimura H, et al. Cancer Commun (Lond). 2019;39:78.
Question 3/5
What is the mechanism of action of the novel agent relatlimab, which is under investigation in combination with nivolumab + CT for stage IV or recurrent NSCLC without driver mutations?

CT, chemotherapy; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; LAG-3, lymphocyte activation gene 3; NSCLC, non-small cell lung cancer; TIGIT, T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains; TIM-3, T cell immunoglobulin and mucin-domain containing-3.
 Correct

LAG-3 is an inhibitory immune checkpoint and a marker of T cell exhaustion. Relatlimab is a
LAG-3-blocking monoclonal antibody that restores effector function in exhausted T cells.

Abbreviation

LAG-3, lymphocyte activation gene 3.

Reference

Morgensztern D, et al. Ann Oncol. 2021;32(Suppl. 5):S1030.

Question 4/5
Your patient has metastatic NSCLC without driver mutations, PD-L1 expression 47% and PS=0. You are considering their suitability for one of the approved PD-1/PD-L1 + CTLA-4 combination therapies (durvalumab + tremelimumab + CT or nivolumab + ipilimumab). Your patient asks for more information about the benefits of the combination therapies based on the latest clinical trial data. What should you tell them?

CT, chemotherapy; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; NSCLC, non-small cell lung cancer; OS, overall survival; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1; PS, performance status; QoL, quality of life; TRAE, treatment-related adverse event.
 Correct

5-year data from the CheckMate 227 trial (NCT02477826) demonstrated improved mOS with the combination of nivolumab + ipilimumab vs CT alone in patients with stage IV or recurrent NSCLC with PD-L1 ≥1% without EGFR/ALK mutations (HR 0.77 [95% CI 0.66–0.91]).1 There was a numerically higher rate of discontinuation due to TRAEs in patients treated with nivolumab + ipilimumab vs CT alone (17% vs 8%).1

In the POSEIDON trial (NCT03164616), the combination of durvalumab + tremelimumab + CT was associated with a significantly improved mOS vs CT alone in patients with metastatic NSCLC without EGFR/ALK mutations regardless of PD-L1 status (HR 0.77 [95% CI 0.65–0.92]; p=0.003).2 There was a numerically higher rate of discontinuation due to TRAEs in the combination group vs CT alone (16% vs 10%).2

Abbreviations

ALK, anaplastic lymphoma kinase; CI, confidence interval; CT, chemotherapy; EGFR, epidermal growth factor receptor; HR, hazard ratio; mOS, median overall survival; NSCLC, non-small cell lung cancer;
TRAE, treatment-related adverse event.

References

  1. Brahmer JR, et al. J Clin Oncol. 2023;41:1200–12.
  2. Johnson ML, et al. J Clin Oncol. 2023;41:1213–27.
Question 5/5
Your patient with metastatic NSCLC without driver mutations is to begin treatment with an ICI + CT. As part of this process, what should you do to best manage their care?

AE, adverse event; CT, chemotherapy; ICI, immune checkpoint inhibitor; irAE, immune-related AE; NSCLC, non-small cell lung cancer.
 Correct

Patients and caregivers need to be educated on the signs and symptoms of potential irAEs, which can occur even after stopping treatment.1 Drug-specific wallet cards help to reinforce the education provided. The cards can also inform healthcare providers about toxic effects associated with immunotherapy and symptom monitoring requirements.1,2

While exercise has numerous benefits for patients with lung cancer, the potential impact of physical activity and exercise remains to be fully appreciated, and no specific exercise guidelines for patients with lung cancer are available.3

Abbreviation

irAE, immune-related adverse event.

References

  1. Naing A, et al. J Immunother Cancer. 2020;8:e001754.
  2. Schneider BJ, et al. J Clin Oncol. 2021;39:4073–126.
  3. Avancini A, et al. Oncologist. 2020;2:e555–e69.
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