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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.

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Lung Cancer CE/CME ACCREDITED Watch Time: 34 minutes

touchTALKS Emerging second-line treatment approaches in advanced NSCLC: The role of ADCs

Dr Rebecca Heist discusses emerging antibody-drug conjugates for the second-line treatment of patients with advanced non-small cell lung cancer.

 
Video chapters
ADCs in NSCLC: Linking structure with mechanism of action

Dr Heist discusses the mechanism of action of ADCs and how each component and their interactions can impact efficacy and safety profiles of an ADC.

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1/3 Next Chapter
 
ADCs in the second-line setting: Exploring the latest clinical trials data

Dr Heist reviews key trial data for ADCs for NSCLC in patients with progressive disease and their implications for clinical practice.

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ADCs in clinical practice: Optimizing treatment for patients with advanced/metastatic NSCLC

Dr Heist looks ahead at how ADCs may be best integrated into clinical practice and the importance of patient selection as well as balancing associated toxicities with efficacy for improved quality of life in patients with advanced NSCLC.

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Overview & Learning Objectives
Overview

In this activity, lung cancer expert Dr Rebecca Heist highlights the role of antibody–drug conjugates (ADCs) in the treatment of patients with advanced non-small cell lung cancer (NSCLC), including their structure and mechanistic rationale, the latest clinical trial data, and key considerations for their application in the clinic.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

This activity has been designed to meet the educational needs of validated oncologists including lung cancer specialists, plus pulmonologists and pathologists involved in the management of NSCLC.

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

Dr Rebecca Heist discloses: Advisory board or panel fees from: AstraZeneca, Daiichi Sankyo, Lilly, Merck, Novartis, Regeneron and Sanofi. Consultancy fees from: AbbVie, Claim Therapeutics and EMD Serono (all relationships terminated).Grants/research support from: AbbVie, Daiichi Sankyo, Erasca, Lilly, Mirati Therapeutics, Mythic Therapeutics, Novartis and Symphogen.

Content Reviewer

Alicia Canalejo, APRN has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Kathy Day 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 0.75 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 0.75 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.

Date of original release: 22 February 2024. Date credits expire: 22 February 2025.

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

Learning Objectives

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

  • Recognize the shared mechanisms of action of ADCs and how their different targets and payloads may inform selection in advanced/metastatic NSCLC
  • Assess the latest clinical trial data for ADCs in patients with advanced/metastatic NSCLC in the second-line setting and identify the advantages and limitations of ADCs
  • Evaluate how ADCs can be integrated into the treatment pathway for patients with advanced/metastatic NSCLC to facilitate disease management
Faculty & Disclosures
Dr Rebecca Heist

Massachusetts General Hospital Cancer Center, Boston, MA, USA

Dr Rebecca Heist is a thoracic oncologist at the Massachusetts General Hospital (MGH) in Boston, MA, USA. read more

Dr Heist is an associate professor of medicine at Harvard Medical School and the Lee Albright and Nile Albright MD Endowed Chair in Clinical Cancer Research at MGH. Her research focuses on novel agents in the treatment of lung cancer, and she is an active member of the Termeer Center at MGH as well as the thoracic oncology group, where she leads first-in-human clinical trials with a focus on lung cancer.

Dr Rebecca Heist discloses: Advisory board or panel fees from: AstraZeneca, Daiichi Sankyo, Lilly, Merck, Novartis, Regeneron and Sanofi. Consultancy fees from: AbbVie, Claim Therapeutics and EMD Serono (all relationships terminated). Grants/research support from: AbbVie, Daiichi Sankyo, Erasca, Lilly, Mirati Therapeutics, Mythic Therapeutics, Novartis and Symphogen.

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Question 1/5
What term is used to describe cytotoxic killing of neighbouring cells in the tumour environment when free payload diffuses out of intracellular sites of ADC catabolism?

ADC, antibody–drug conjugate.
Correct

‘Bystander effect’ is the term used to refer to the ability of a free payload to diffuse from the intracellular target site of ADC catabolism, where cytotoxic payloads are released, into neighbouring cells within the tumour environment. This effect can amplify the anti-tumour effect of the ADC, but also contribute to off-target toxicities through entry into normal, non-malignant tissue.

Abbreviation

ADC, antibody–drug conjugate.

Reference

Nguyen TD, et al. Cancers (Basel). 2023;15:713.

Question 2/5
Your patient has advanced EGFR wild type NSCLC adenocarcinoma and has progressed on systemic therapy. Biomarker testing with IHC reveals high c-Met expression. Assuming all options are approved and available in your region, which ADC would you select for this patient?

ADC, antibody–drug conjugate; c-Met, mesenchymal epithelial transition factor; EGFR, epidermal growth factor receptor; IHC, immunohistochemistry; NSCLC, non-small cell lung cancer.
Correct

Telisotuzumab vedotin is a c-Met-targeting ADC. Data from the LUMINOSITY clinical trial of telisotuzumab vedotin in patients with previously treated, advanced/metastatic NSCLC demonstrated greater ORR in the c-Met high group (≥50% 3+ by IHC) compared with the c-Met intermediate group (25 to <50% 3+ by IHC) among those with EGFR wild type non-squamous NSCLC (52% vs 24%, respectively) and those with EGFR mutant non-squamous NSCLC (17% vs 0%, respectively).

Abbreviations

ADC, antibody–drug conjugate; c-Met, mesenchymal epithelial transition factor; EGFR, epidermal growth factor receptor; IHC, immunohistochemistry; NSCLC, non-small cell lung cancer.

Reference

Camidge DR, et al. J Clin Oncol. 2022;40(Suppl. 16):9016.

Question 3/5
Your patient with advanced NSCLC and brain metastasis is initiating treatment with trastuzumab deruxtecan 5.4 mg/kg. Based on data from the post hoc DESTINY-Lung01 and DESTINY-Lung02 pooled analysis, which statement would you include when discussing expected intracranial outcomes?

NSCLC, non-small cell lung cancer.
Correct

A post hoc analysis of pooled data from DESTINY-Lung01 and DESTINY-Lung02 in patients with unresectable/metastatic NSCLC and measurable brain metastasis showed a reduction in brain lesion size from baseline in 12/14 (86%) patients receiving trastuzumab deruxtecan 5.4 mg/kg. The intracranial objective response rate and intracranial disease control rate in this population were 50% and 93%, respectively.

Abbreviation

NSCLC, non-small cell lung cancer.

Reference

Li BT, et al. Presented at: ESMO Congress 2023, Madrid, Spain. 20–24 October 2023. Presentation 1321MO.

Question 4/5
Your patient with advanced NSCLC is initiating treatment with a deruxtecan-containing ADC and you are mindful of the potential associated pulmonary toxicities. Which of the following would you ideally include in your practice to minimize the risk and impact of ILD in this patient?

ADC, antibody–drug conjugate; CT, computed tomography; ILD, interstitial lung disease; NSCLC, non-small cell lung cancer.
Correct

ILD has been reported in patients with advanced NSCLC treated with trastuzumab deruxtecan, patritumab deruxtecan or datopotamab deruxtecan in the clinical trial setting.1–3 Based on real-world practices for managing trastuzumab deruxtecan-related ILD, five Sstrategies have emerged as key steps for minimizing the risk and impact of ILD.4 Of these, the ‘Scan’ strategy recommends high-resolution CT scans of the chest at baseline, and repeat scans every 6–12 weeks.4

Abbreviations

CT, computed tomography; ILD, interstitial lung disease; NSCLC, non-small cell lung cancer.

References

  1. Goto K, et al. J Clin Oncol. 2023;41:4852–63.
  2. Yu HA, et al. J Clin Oncol. 2023;41:5363–75.
  3. Ahn MJ, et al. Presented at: ESMO Congress 2023, Madrid, Spain. 20–24 October 2023. Presentation LBA12.
  4. Tarantino P, Tolaney SM. JCO Oncol Pract. 2023;19:526–7.
Question 5/5
Your patient with advanced EGFR-mutated NSCLC and no other known actionable genomic alterations has shown disease progression following third-generation EGFR TKI therapy and platinum-based chemotherapy. Testing reveals an EGFR TKI resistance–associated genomic alteration. Based on current data and assuming all options are approved and available in your region, which ADC would you recommend for this patient?

ADC, antibody–drug conjugate; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor.
Correct

The phase II HERTHENA-Lung01 trial showed that patritumab deruxtecan was associated with a median PFS of 5.5 months and a median OS of 11.9 months in patients with EGFR-mutated locally advanced or metastatic NSCLC and progression following EGFR TKI and platinum-based chemotherapy. Responses were seen across tumours harbouring EGFR-dependent, EGFR-independent or unidentified mechanisms of resistance and in patients with EGFR C797X or MET amplification, the most common mechanisms of resistance to third-generation EGFR TKIs.

Abbreviations

EGFR, epidermal growth factor receptor; MET, mesenchymal epithelial transition proto-oncogene, receptor tyrosine kinase; NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression-free survival; TKI, tyrosine kinase inhibitor.

Reference

Yu HA, et al. J Clin Oncol. 2023;41:5363–75.

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