Lung Cancer CME ACCREDITED Watch Time: 38 mins

touchPANEL DISCUSSION Deciphering the data in EGFR-mutant NSCLC: What have we learned in 2021?

Watch experts in lung cancer discuss the evolving treatment options for patients with EGFR-mutant NSCLC, as well as the importance of biomarker testing in determining the best treatment approaches for patients with early-stage or metastatic disease.

Dr Pasi Jänne

Dana-Farber Cancer Institute,
Boston, MA, USA

CHAIR

Panelists:
Dr Thanyanan Reungwetwattana, Dr Neal Navani
 
Video Chapters
Introduction

Dr Pasi Jänne introduces the panel of leading experts in thoracic oncology, and outlines the agenda for discussion on the latest data in EGFR-mutant NSCLC.

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1/4 Next Chapter
 
How is the use of EGFR-TKIs evolving in NSCLC?

The expert panel discusses the impact of the changing treatment landscape in locally-advanced and metastatic EGFR-mutant NSCLC, and highlights the latest evidence for novel combination therapies.

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2/4 Next Chapter
 
How important is it that clinicians increase their focus on biomarker testing?

The panel discusses the expanding role of biomarker testing in NSCLC, the rationale for broad panel next-generation sequencing, and when to use liquid versus tissue biopsy for optimal treatment decision making.

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3/4 Next Chapter
 
What are the options for patients progressing on EGFR-inhibitors?

The expert panel reviews the latest data on acquired resistance mechanisms to EGFR-TKIs, and how emerging therapies may impact the the requirement for molecular testing and the treatment paradigm in patients with progressive disease.

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Overview & Learning Objectives
Overview

Experts in lung cancer discuss recent developments in the treatment of EGFR-mutant NSCLC, including biomarker testing and emerging treatments for managing patients with early-stage and metastatic disease. The experts will highlight important data recently presented at the World Congress on Lung Cancer (WCLC) and European Society of Medical Oncology (ESMO) Congress 2021 that will likely impact future clinical practice.

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 oncologists, pulmonologists, radiation oncologists, thoracic surgeons, pathologists and oncology nurse specialists

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

Dr Pasi Jänne discloses: Consultant fees from AbbVie, Accutar Biotechnology, Inc., Acea Biosciences, Allorion Therapeutics, Araxes Pharmaceuticals, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Esai Pharmaceuticals, Gatekeeper Pharmaceuticals, Genentech, Ignyta, LOXO Oncology, Mirati Therapeutics, Novartis, Nuvalent, Pfizer, Roche, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax Pharmaceuticals, Takeda Oncology, Transcenta and Vornoi; grants/research support from Astellas Pharmaceuticals, AstraZeneca, Daiichi Sankyo, PUMA Biotechnology, Revolution Medicines and Takeda Oncology.

Dr Thanyanan Reungwetwattana discloses: Advisory board/panel discussion fees from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda and Yuhan Corp; grants/research support from AstraZeneca, Merck Sharp & Dohme, Roche and Yuhan Corp.

Dr Neal Navani discloses: Advisory board/panel discussion fees from Amgen, AstraZeneca, Janssen, Lilly, Merck Sharp & Dohme, Modo Bio and Olympus Corporation; speaker’s bureau fees from Amgen, AstraZeneca, Bristol Myers Squibb and Janssen.

Content Reviewer

Ryan N Bookout, PharmD, BCOP discloses: Stocks (self-managed) from Bristol Myers Squibb, Gilead, Novartis and Spectrum Pharmaceuticals (all relationships terminated).

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: 28 October 2021. Date credit expire: 28 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:

  • Describe how the use of EGFR-TKIs in patients with EGFR-mutant NSCLC is evolving
  • Explain the importance of timely biomarker testing at diagnosis and throughout treatment for patients with EGFR-mutant NSCLC
  • Recall latest data for therapy options post-resistance to EGFR-TKIs in patients with advanced EGFR-mutant NSCLC
Faculty & Disclosures
Dr Pasi Jänne

Dana-Farber Cancer Institute, Boston, MA, USA

Pasi Jänne, MD, PhD, is the Director of the Lower Center for Thoracic Oncology at Dana-Farber Cancer Institute, and a Professor of Medicine at Harvard Medical School, Boston, MA, USA. He is also the Director of the Belfer Center for Applied Cancer Science at the Dana-Farber Cancer Institute, Boston, MA, USA. read more

Dr Jänne’s research combines laboratory-based studies, with translational research and clinical trials of novel therapeutic agents in patients with lung cancer. His main research interests centre around understanding and translating the therapeutic importance of oncogenic alterations in lung cancer. He has made seminal therapeutic discoveries, including being a co-discoverer of EGFR mutations, and findings from his work have led to the development of several clinical trials.

Dr Jänne has received several awards for his work, including from the American Association for Cancer Research, European Society for Medical Oncology and the American Society of Clinical Oncology.

Dr Pasi Jänne discloses: Consultant fees from AbbVie, Accutar Biotechnology, Inc., Acea Biosciences, Allorion Therapeutics, Araxes Pharmaceuticals, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Esai Pharmaceuticals, Gatekeeper Pharmaceuticals, Genentech, Ignyta, LOXO Oncology, Mirati Therapeutics, Novartis, Nuvalent, Pfizer, Roche, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax Pharmaceuticals, Takeda Oncology, Transcenta and Vornoi; grants/research support from Astellas Pharmaceuticals, AstraZeneca, Daiichi Sankyo, PUMA Biotechnology, Revolution Medicines and Takeda Oncology.

Dr Thanyanan Reungwetwattana

Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Thanyanan Reungwetwattana, MD, is a Consultant Oncologist in the Faculty of Medicine at the Ramathibodi Hospital in Thailand. read more

Dr Reungwetwattana’s research interests are in lung cancer and drug development in both clinical and translational settings.

Dr Reungwetwattana is on the Editorial Board of the Journal of Thoracic Oncology. She has also served on a number of congress programme committees, including the regional organizing committee for the World Conference on Lung Cancer (WCLC) 2020–2021. She recently joined the scientific committee of the European Society for Medical Oncology (ESMO).

Dr Reungwetwattana was awarded Best Young Physician of the Year from The Royal College of Physicians of Thailand in 2021, as well as being a 2020 National finalist for the ASEAN-US Science Prize for Women.

Dr Thanyanan Reungwetwattana discloses: Advisory board/panel discussion fees from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda and Yuhan Corp; grants/research support from AstraZeneca, Merck Sharp & Dohme, Roche and Yuhan Corp.

Dr Neal Navani

University College London, London, UK

Neal Navani, MA, MSc, PhD, FRCP, is Lead Clinician for the lung cancer service at University College London (UCLH), UK. read more

Dr Navani also chairs the Lung Cancer Board for the North Central and East London Cancer Alliance, and is on the steering groups of the British Thoracic Oncology Group, UK Lung Cancer Coalition and Thoracic Oncology board of the American Thoracic Society. In 2021, Dr Navani was appointed a member of the NHS England Lung Cancer Clinical Expert Group.

Dr Navani currently holds a Cancer Research UK (CRUK) grant for the early diagnosis of lung cancer, and a separate CRUK grant for developing novel methods for cancer data collection. In 2020, Dr Navani won a prestigious Medical Research Council/National Institute for Health Research fellowship to research predictors of cancer in lung nodules. He is senior clinical lead of the UK National Lung Cancer Audit and is the respiratory representative on the current NICE lung cancer guideline and quality standards.

Dr Neal Navani discloses: Advisory board/panel discussion fees from Amgen, AstraZeneca, Janssen, Lilly, Merck Sharp & Dohme, Modo Bio and Olympus Corporation; speaker’s bureau fees from Amgen, AstraZeneca, Bristol Myers Squibb and Janssen.

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Question 1/5
For patients with stage III NSCLC who undergo surgical resection with curative intent, and whose resected tissue shows that the tumour is positive for the EGFR exon 21 L858R mutation, which of the following would be your preferred treatment option?

EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer.
Correct

The ADAURA trial assessed the efficacy and safety of osimertinib as adjuvant therapy in completely resected EGFR-mutant NSCLC (NCT02511106, phase III).1 Prior adjuvant chemotherapy was allowed but not mandatory.1 In patients with stage IB–IIIA EGFR-mutant NSCLC, DFS was significantly longer among those who received osimertinib than among those who received placebo.1 Of note, the observed DFS benefit with osimertinib was irrespective of whether patients received adjuvant chemotherapy or not.1

Following the results of the ADAURA trial, osimertinib was approved by both the US Food and Drug Administration and the European Medicines Agency as targeted adjuvant therapy after tumour resection in adult patients with NSCLC whose tumours have EGFR exon 19 deletions or exon 21 L858R mutations.2,3

The IMpower010 (NCT02486718) trial enrolled patients with completely resected stage IB–IIIA NSCLC. Patients received adjuvant cisplatin-based chemotherapy, and were subsequently randomized to receive further adjuvant treatment with atezolizumab or best supportive care.4 Atezolizumab demonstrated a statistically significant DFS benefit compared with best supportive care in patients with stage II–IIIA tumour with PD-L1 expression ≥1%.4 However, in this study, patients were not selected based on the presence of oncogenic target mutations, and clinical trial data have demonstrated a lack of efficacy in patients with EGFR-mutant NSCLC.5,6 In addition, in a subgroup analysis of the IMpower010 trial, which investigated atezolizumab vs best supportive care after adjuvant chemotherapy in resected stage IB–IIIA NSCLC, there was no benefit with atezolizumab in patients whose tumour harboured an EGFR mutation.7

Abbreviations
DFS, disease-free survival; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; PD-L1, programmed death-ligand 1.

References

  1. Wu Y-L, et al. N Engl J Med. 2020;383:1711–23.
  2. FDA. Osimertinib. Prescribing information. 2021. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/208065s022lbl.pdf (accessed 7 October 2021).
  3. EMA. Osimertinib. Summary of product specifications. Available at: www.ema.europa.eu/en/documents/product-information/tagrisso-epar-product-information_en.pdf (accessed 7 October 2021).
  4. Wakelee HA, et al. J Clin Oncol. 2021;39(Suppl. 15):8500.
  5. Lisberg A, et al. J Clin Oncol. 2018;13:1138–45.
  6. Velez MA, et al. Transl Lung Cancer Res. 2019;8:S339–42.
  7. Wakelee HA, et al. Presented at the American Association for Clinical Oncology (ASCO) June 2021. Abstr #8500.
Question 2/5
Which of the following statements, regarding the use of bevacizumab in combination with either a first- or third-generation EGFR-TKI in the first-line setting, accurately reflects the reported outcomes presented at the ESMO Congress 2021 in patients with metastatic EGFR-mutant NSCLC?

EGFR, epidermal growth factor receptor; ESMO, European Society for Medical Oncology; PFS, progression-free survival; TKI, tyrosine kinase inhibitor.
Correct

The BEVERLY trial, comparing bevacizumab plus erlotinib vs erlotinib alone, reported positive outcomes, demonstrating a median PFS of 15.4 vs 9.6 months, respectively. In a subgroup analysis of former/current smokers vs never smokers, a greater benefit in terms of PFS was observed for the combination therapy relative to monotherapy in former/current smokers (HR 0.90, 95% CI 0.52–1.57). In the never smokers, erlotinib alone was favoured (HR 0.49, 95% CI 0.28–0.82).1

In the WJ0G9717L trial, the median PFS for patients receiving bevacizumab plus osimertinib did not show significance: 22.1 months vs 20.2 months for patients receiving osimertinib alone. A subgroup analysis of patients receiving bevacizumab plus osimertinib found that the median PFS in former/current smokers was 32.4 months vs 20.3 months for never smokers. While in the patients receiving osimertinib alone, the median PFS for former/current smokers was 13.6 months vs 32.5 months for never smokers.2

Overall, both trials suggest that combining bevacizumab with an EGFR-TKI may be beneficial in former/current smokers. In addition, no unexpected safety signals were reported.1,2

Abbreviations
CI, confidence interval; EGFR, epidermal growth factor receptor; HR, hazard ratio; PFS, progression-free survival; TKI, tyrosine kinase inhibitor.

References

  1. Piccirillo MC, et al. Ann Oncol. 2021;32 (Suppl. 5):S949–1039.
  2. Kenmotsu H, et al. Ann Oncol. 2021;32 (Suppl. 5):S1283–346.
Question 3/5
What is the significance of the results of the CLEAR study, evaluating the clinical utility of liquid biopsy (cfDNA) for the diagnosis of EGFR-mutant advanced lung cancer in clinical practice?

cfDNA, circulating-free DNA; EGFR, epidermal growth factor receptor.
Correct

The CLEAR trial evaluated the clinical and economic impact of using cfDNA to diagnose lung cancer early. Patients were included while undergoing investigation for radiological suspicion of stage III/IV advanced cancer. About 9% of patients had no adequate tissue to perform molecular analysis, and 10% of patients had undergone at least two biopsies.

The median time to receipt of results was significantly shorter for cfDNA (7 days vs 27 days with tissue biopsy, p<0.0001). The rate of mutations detected was 9% and 11% by cfDNA and tissue biopsy, respectively. Mutation detection by cfDNA was found to be 84.6% sensitive and 100% specific.

Osimertinib treatment was initiated within 2–27 days of the cfDNA results and 0–21 days before tissue diagnosis in five out of nine patients.

Abbreviations
cfDNA, circulating-free DNA.

Reference
Nassabein R, et al. Ann Oncol. 2021;32 (Suppl. 5):S949–1039

Question 4/5
A patient with advanced EGFR-mutant NSCLC, receiving first-line osimertinib, undergoes ctDNA analysis by droplet-digital PCR, and is found to have a detectable EGFR mutation at baseline, and clearance at week 3. What are the implications of this finding based on the AURA3 results recently presented at the World Lung Cancer Congress 2021?

ctDNA, circulating tumour DNA; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; PCR, polymerase chain reaction.
Correct

The association between the early clearance of EGFR-mutation in ctDNA and clinical outcomes was investigated as part of the AURA3 trial in patients treated with either osimertinib or platinum-pemetrexed.

Among patients with a valid droplet-digital PCR result, the absence of EGFR mutation in ctDNA at baseline corresponded with a favourable median PFS. In the osimertinib arm (n=209), median PFS was 14.0 months in patients without a baseline EGFR mutation vs 8.3 months in those with baseline EGFR mutation. In the platinum-pemetrexed arm (n=82), median PFS was 5.8 months in patients without baseline EGFR mutation vs 4.2 months in those with baseline EGFR mutation.

Patients who achieved clearance of EGFR-mutation in ctDNA at week 3 vs those who did not also had more favourable outcomes in both the osimertinib (median PFS: 10.9 vs 5.7 months) and platinum-pemetrexed (median PFS: 6.2 vs 4.2 months) treatment arms.

Abbreviations
ctDNA, circulating tumour DNA; EGFR, epidermal growth factor receptor; PCR, polymerase chain reaction; PFS, progression-free survival.

Reference
Ahn MJ, et al. Presented at: 2021 World Conference on Lung Cancer Singapore, 8–14 September 2021. Abstr FP16.03

Question 5/5
The use of amivantanib +/- lazertinib has been evaluated in patients progressing on standard of care osimertinib with or without intervening platinum-based chemotherapy. Based on the preliminary results of the CHRYSALIS and CHRYSALIS-2 studies, which of the following options is preferred for best outcomes in patients after failure of osimertinib?
Correct

Findings from the CHRYSALIS and CHRYSALIS-2 studies suggest amivantamab plus lazertinib demonstrates antitumour activity in populations that have progressed on both standard of care osimertinib and platinum chemotherapy.1

In CHRYSALIS, post-osimertinib treatment, the ORR for patients treated with amivantamab plus lazertinib was 36% vs 19% for amivantamab alone. The median DOR for the two groups was 9.6 months vs 5.9 months, respectively.1

In CHRYSALIS-2, post-platinum chemotherapy, the ORR was 41% in the study target group (2–3 prior lines) vs 21% in a heavily pretreated group (≥4 lines). The CBR was 69% and 51% respectively for the two groups.2

In conclusion, the study authors state that activity of amivantamab plus lazertinib is not impacted by the use of intervening chemotherapy.2

Abbreviations
CBR, clinical benefit rate; DOR, duration of response; ORR, objective response rate.

References

  1. Leighl NB, et al Ann Oncol. 2021;32(Suppl. 5):S949–1039.
  2. Shu CA, et al. Ann Oncol. 2021;32(Suppl. 5):S949–1039.
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