Lung Cancer, Immunotherapy CE/CME ACCREDITED Watch Time: 64 mins

touchCONGRESS Optimizing frontline immunotherapy for advanced NSCLC

Watch this two-part activity exploring recent developments on the use of frontline immunotherapeutic strategies in patients with advanced non-small cell lung cancer (NSCLC). Filmed following the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and European Society for Medical Oncology (ESMO) Congress 2021.

Part 1: Watch thoracic oncology expert Prof. Edward Garon review key data from the 2021 ASCO Annual Meeting and ESMO Congress 2021 Watch Now
Part 2: Choose from leading experts who discuss what these data may mean for global and regional practice Select An Interview

  • Part 1: Data Review
CE/CME ACCREDITED Next Chapter
Introduction
Update on immunotherapy in the frontline setting in advanced NSCLC
Emerging biomarkers guiding immunotherapy treatment decisions in advanced NSCLC
Optimizing frontline immunotherapy in the management of advanced NSCLC
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Overview

Watch Prof. Edward Garon contextualize potential implications of the latest data on frontline immunotherapy in advanced non-small cell lung cancer (NSCLC), presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Society for Medical Oncology (ESMO) Congress 2021. During the presentation, Dr Garon considers:

  • The latest updates on frontline immunotherapy in advanced NSCLC
  • Emerging biomarkers guiding immunotherapy treatment decisions for patients with advanced NSCLC in the frontline setting
  • Approaches to optimize frontline immunotherapy in the clinical management of advanced NSCLC

Edward Garon is the Director of the Thoracic Oncology Program at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles (UCLA). He earned a bachelor’s degree in biology at the Massachusetts Institute of Technology. His medical doctorate was from Washington University in St. Louis. He performed his internship and residency at the University of Chicago. After a chief residency at Cook County Hospital in Chicago, he was a fellow in haematology and oncology at UCLA. He has remained at UCLA ever since and is currently Professor of Medicine. He also received a master’s degree in clinical investigation from UCLA. read more

He has been the principal investigator of peer-reviewed grants from various funding organizations, including the National Cancer Institute. His focus is on clinical research and biomarker development. He has served as the principal investigator on national and international phase I, II and III clinical trials, including trials that have led to the approval of multiple drugs and a companion diagnostic.

Disclosures

Prof. Edward Garon discloses: Advisory board or panel fees from ABL Bio, Boehringer-Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, EMD Serono, Eisai, GlaxoSmithKline, Merck, Natera, Novartis, Regeneron, Sanofi, Shionogi and Xilio Therapeutics; and Grants/research support from AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, Lilly, EMD Serono, Genentech, Lovance Biotherapeutics, Merck, Mirati Therapeutics, Neon Healthcare and Novartis.

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  • Part 2: Expert Interviews
Prof. Edward Garon
Watch Time: 09:15 David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA

Prof. Edward Garon considers the latest data on frontline immunotherapy in advanced NSCLC, presented at the 2021 ASCO Annual Meeting and ESMO Congress 2021.
 
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Prof. Anne-Marie Dingemans
Watch Time: 10:16 Erasmus Medical Center, Rotterdam, The Netherlands

Prof. Anne-Marie Dingemans considers the latest data on frontline immunotherapy in advanced NSCLC, presented at the 2021 ASCO Annual Meeting and ESMO Congress 2021.
 
 
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Dr Raffaele Califano
Watch Time: 08:23 The Christie Hospital and Manchester University Hospital, Manchester, UK

Dr Raffaele Califano considers the latest data on frontline immunotherapy in advanced NSCLC, presented at the 2021 ASCO Annual Meeting and ESMO Congress 2021.
 
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Prof. Edward Garon
 David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA Watch Time: 09:15 Translations available:
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Prof. Anne-Marie Dingemans
 Erasmus Medical Center, Rotterdam, The Netherlands Watch Time: 10:16 Translations available:
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Dr Raffaele Califano
 The Christie Hospital and Manchester University Hospital, Manchester, UK Watch Time: 08:23 Translations available:
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Overview & Learning Objectives
Overview

Watch our expert faculty contextualize potential implications of the latest data on frontline immunotherapy in advanced non-small cell lung cancer (NSCLC), presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Society for Medical Oncology (ESMO) Congress 2021. During the presentation, they consider:

  • The latest updates on frontline immunotherapy in advanced NSCLC
  • Emerging biomarkers guiding immunotherapy treatment decisions for patients with advanced NSCLC in the frontline setting
  • Approaches to optimize frontline immunotherapy in the clinical management of advanced NSCLC

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 practising oncology and respiratory specialists, with a focus on lung cancer specialists and pulmonologists involved in the management of NSCLC.

Disclosures

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. Edward Garon discloses: Advisory board or panel fees from ABL Bio, Boehringer-Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, EMD Serono, Eisai, GlaxoSmithKline, Merck, Natera, Novartis, Regeneron, Sanofi, Shionogi and Xilio Therapeutics; and Grants/research support from AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, Lilly, EMD Serono, Genentech, Lovance Biotherapeutics, Merck, Mirati Therapeutics, Neon Healthcare and Novartis.

Prof. Anne-Marie Dingemans discloses: Advisory board or panel fees from Amgen, Bayer, Boehringer Ingelheim, Pharmamar, Roche and Sanofi; and Honoraria from AstraZeneca, Lilly, Janssen, Pfizer and Takeda.

Dr Raffaele Califano discloses: Advisory board or panel fees from: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme and Roche; Consultancy fees from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme and Roche; and Speaker bureau fees from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme and Roche.

Content Reviewer

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

Touch Medical Director

Christina Mackins-Crabtree 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 1.5 AMA PRA Category 1 CreditsTM. 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 1.5 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: 07 October 2021. Date credit expire: 07 October 2022.

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

Learning Objectives

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

  • Summarize recent data evaluating frontline single-agent immunotherapy or combination strategies for advanced NSCLC
  • Assess potential biomarkers that may be used to identify patients with advanced NSCLC who may benefit from frontline immunotherapy
  • Outline effective management strategies using frontline immunotherapeutic strategies for patients with advanced NSCLC
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This Activity Is Funded By:

This activity is funded by an independent medical education grant from Regeneron Pharmaceuticals, Inc. and Sanofi Genzyme. This medical education is jointly provided by USF Health and touchIME.

The information provided by this CE 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 CE 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: 07 October 2021. Date credits expire: 07 October 2023.

This content is intended for healthcare professionals only. Please confirm that you are a healthcare professional.

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Question 1/5
Based on 4- and 2-year updates from the CheckMate 227 and CheckMate 9LA trials presented at ASCO 2021, what have we learned about long-term clinical outcomes with frontline IO in advanced NSCLC?

ASCO, American Society of Clinical Oncology; ChT, chemotherapy; IO, immunotherapy; NSCLC, non-small cell lung cancer; PD-L1, programmed death ligand-1.
 Correct

Updated efficacy results from CheckMate 227 showed frontline combination IO (nivolumab plus ipilimumab) achieved sustained long-term clinical benefits in patients with advanced NSCLC, compared with ChT. Improvements in 4-year OS and DOR, regardless of PD-L1 expression (≥1%, ≥50% or ≥1%), were reported.1

Updated 2-year efficacy data from CheckMate 9LA also reported long-term improvements in OS with frontline combination IO (nivolumab plus ipilimumab) compared with ChT alone, in patients with advanced NSCLC, regardless of PD-L1 expression level.2

ChT, chemotherapy; DOR, duration of response; NSCLC, non-small cell lung cancer; OS, overall survival; PD-L1, programmed death ligand-1.

References

  1. Paz-Ares LG, et al. J Clin Oncol. 2021;39(Suppl. 15):9016. Presented at: ASCO21 Virtual, 4–8 June 2021.
  2. Reck M, et al. J Clin Oncol. 2021;39(Suppl. 15):9000. Presented at: ASCO21 Virtual, 4–8 June 2021.
Question 2/5
Which of the following statements best summarizes the current status of PD-L1 as a biomarker guiding treatment decisions surrounding the use of frontline IO in advanced NSCLC?

ChT, chemotherapy; IO, immunotherapy; NSCLC, non-small cell lung cancer; PD-L1; programmed death ligand-1.
 Correct

Currently approved frontline IO-ChT combination regimens (e.g. atezolizumab/bevacizumab, nivolumab/ipilimumab or pembrolizumab, plus ChT) in oncogene driver negative advanced NSCLC may be considered, regardless of tumour PD-L1 status.1–8

Currently approved frontline single-agent IO indicates use in advanced NSCLC with PD-L1 ≥50%.1,2,7–10 Recent NCCN Guidelines recommend use of frontline single-agent pembrolizumab in oncogene driver negative NSCLC with PD-L1 1–49%.11

Current guidelines recommend molecular testing for oncogenic aberrations and evaluation of PD-L1 status in advanced NSCLC.11,12 Although PD-L1 expression may be elevated in NSCLC tumours harbouring an oncogene driver mutation, the NCCN recommend physicians should obtain molecular testing results for actionable biomarkers for targeted therapies before administering frontline IO, if clinically feasible.11

ChT, chemotherapy; IO, immunotherapy; NCCN, National Comprehensive Cancer Network; NSCLC, non-small cell lung cancer; PD-L1; programmed death ligand-1.

References 

  1. US FDA. Prescribing information: atezolizumab. February 2021. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/761034s033s034s035s036s037s038lbl.pdf (accessed September 2021).
  2. EMA. Summary of product characteristics: atezolizumab. September 2021. Available at: www.ema.europa.eu/en/documents/product-information/tecentriq-epar-product-information_en.pdf (accessed September 2021). 
  3. US FDA. Prescribing information: nivolumab. January 2021. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/125554s090lbl.pdf (accessed September 2021).
  4. EMA. Summary of product characteristics: nivolumab. September 2021. Available at: www.ema.europa.eu/en/documents/product-information/opdivo-epar-product-information_en.pdf (accessed September 2021). 
  5. US FDA. Prescribing information: ipilimumab. May 2020. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2020/125377s110lbl.pdf (accessed September 2021).
  6. EMA. Summary of product characteristics: ipilimumab. May 2020. Available at: www.ema.europa.eu/en/documents/product-information/yervoy-epar-product-information_en.pdf  (accessed September 2021).
  7. US FDA. Prescribing information: pembrolizumab. March 2021. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s096lbl.pdf (accessed September 2021).
  8. EMA. Summary of product characteristics: pembrolizumab. March 2020. Available at: www.ema.europa.eu/en/documents/product-information/keytruda-epar-product-information_en.pdf  (accessed September 2021).
  9. US FDA. Prescribing information: cemiplimab. February 2021. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/761097s007lbl.pdf (accessed September 2021).
  10.  EMA. Summary of product characteristics: cemiplimab. May 2021. Available at: www.ema.europa.eu/en/documents/product-information/libtayo-epar-product-information_en.pdf  (accessed September 2021).
  11.  NCCN Clinical Practice Guidelines in Oncology: Non-small cell lung cancer. Version 5.2021.
  12.  Planchard D, et al. Ann Oncol. ESMO Guidelines 2020 update. Originally published 2018: Ann Oncol. 2018;29(Suppl 4): iv192–iv237.
Question 3/5
An updated efficacy and safety analysis from CheckMate 227 presented at ASCO21 explored the impact of treatment discontinuation with frontline dual IO (nivolumab and ipilimumab) following TRAEs. Which of the following statements best reflects the authors’ findings regarding clinical outcomes following treatment discontinuation in this cohort?

DOR, duration of response; IO, immunotherapy; PD-L1, programmed cell death ligand-1; TRAE, treatment-related adverse event.
 Correct

In the updated safety and efficacy analysis from CheckMate 227, over half (53%) of responders with PD-L1 ≥1% maintained their treatment response for ≥3 years following discontinuation of frontline dual-IO (nivolumab and ipilimumab), compared with 48% of responders with any PD-L1 expression (PD-L1 ≥1% and <1%). 

Reported 4-year OS rates following discontinuation of dual-IO were comparable between the any-PD-L1 expression (PD-L1 ≥1% and <1%) and PD-L1 ≥1% subgroups (both 44%; 41.5 months vs 30.6 months, respectively). DOR after treatment discontinuation was longer in the PD-L1 ≥1% subgroup (52.6 months) compared with the any-PD-L1 expression subgroup (34.2 months). Data from the PD-L1 <1% subgroup as a discrete cohort were not presented in these analyses.

DOR, duration of response; IO, immunotherapy; OS, overall survival; PD-L1, programmed cell death ligand-1; TRAE, treatment-related adverse event.

Reference

Paz-Ares LG, et al. J Clin Oncol. 2021;39(Suppl. 15):9016. Presented at: ASCO21 Virtual, 4–8 June 2021.

Question 4/5
Your patient, a 65-year-old, never smoker, is diagnosed with advanced NSCLC and assessed as ECOG PS 1. Genetic profiling reveals no actionable genetic mutations and PD-L1 55%. MRI shows brain metastases, but have been deemed clinically stable over the prior 4 weeks; which of the following regimens might you consider in the management of this patient?

<small? ChT, chemotherapy; ECOG PS, Eastern Cooperative Oncology Group performance status; IO, immunotherapy; MRI, magnetic resonance imaging; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PD-L1, programmed cell death-ligand-1; PFS, progression-free survival.
 Correct

Current guidelines recommend IO monotherapy (atezolizumab, cemiplimab or pembrolizumab) for patients with advanced/metastatic oncogene driver mutation-negative NSCLC with PD-L1 ≥50% and ECOG PS 0–1.1,2

Of particular relevance to this patient case, with clinically stable brain metastases, were results presented at ASCO21 from a sub analysis of the EMPOWER Lung-1 study. The analysis showed that cemiplimab monotherapy represents a suitable option for this group of patients, with OS, PFS and ORR improved compared with ChT.3 

ChT, chemotherapy; ECOG PS, Eastern Cooperative Oncology Group performance status; IO, immunotherapy; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PD-L1, programmed cell death ligand-1; PFS, progression-free survival.

References

  1. NCCN Clinical Practice Guidelines in Oncology: Non-small cell lung cancer. Version 5.2021. 
  2. Planchard D, et al. Ann Oncol.  ESMO Guidelines 2020 update. Originally published 2018: Ann Oncol. 2018;29(Suppl 4): iv192–iv237.
  3. Ozguroglu M, et al. J Clin Oncol. 2021;39(Suppl. 15):9085. Presented at: ASCO21 Virtual, 4–8 June 2021.
Question 5/5
Based on pooled analyses of the phase III IMpower trials, how would you manage expectations with respect to irAEs for your patients with advanced NSCLC who are receiving 1L atezolizumab-based treatment regimens?

1L, frontline; irAE, immune-related adverse event; NSCLC, non-small-cell lung cancer; OS, overall survival.
 Correct

The phase III IMpower130, IMpower132 and IMpower150 trials evaluated atezolizumab (atezo) + ChT ± bevacizumab as 1L therapy for NSCLC. Socinski MA, et al. explored the association between irAEs and efficacy in these trials. Any-grade irAEs occurred in 48% (atezo) and 32% (control) of patients; grade 3–5 irAEs occurred in 11% (atezo) and 5% (control). The most common irAEs were rash, hepatitis and hypothyroidism. Of note in this pooled analysis, patients with irAEs had longer OS versus patients without irAEs in the atezo-containing and control arms.

1L, frontline; irAE, immune-related adverse event; NSCLC, non-small-cell lung cancer; OS, overall survival.

Reference

Socinski MA, et al. J Clin Oncol. 2021;39(Suppl. 15):9002. Presented at ASCO21 Virtual, 04–08 June 2021.

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