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WCLC 2023 Highlights
2023 World Conference on Lung Cancer Preview: Experts Choose the Top Abstracts

Released: August 30, 2023

Matthew Gubens
Matthew Gubens, MD, MS, FASCO
Helena Yu
Helena Yu, MD
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The International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer (WCLC) will feature notable results from numerous clinical trials in lung cancer. Lung cancer experts Matthew Gubens, MD, MS, and Helena Yu, MD, have identified their most anticipated abstracts, which we will cover online as part of CCO’s Independent Conference Coverage of WCLC 2023. Remember to check the CCO website often as the meeting unfolds for timely downloadable slidesets summarizing the data from these studies and then again for a CME-certified online text module featuring expert analysis of how the new data will affect clinical practice. [link: WCLC 2023 PROGRAM PAGE] (Editor’s note: All links below go to the session on the WCLC 2023 program website where individual abstracts can be found.)

The most noteworthy studies include:

  • FLAURA2: phase III trial evaluating first-line osimertinib plus platinum-based chemotherapy vs osimertinib alone in patients with EGFR-mutated advanced non-small-cell lung cancer (NSCLC) (abstract PL03.13)
    • Single-agent osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), is the standard of care for newly diagnosed EGFR-mutated advanced NSCLC based on the phase III FLAURA trial. However, acquired resistance to osimertinib is inevitable. We know from a press release that intensification of first-line treatment by adding chemotherapy to osimertinib achieves a progression-free survival benefit in this patient population, but will its magnitude be enough to make this a standard of care despite the added toxicity? Will we learn from subgroup analyses how to select patients with higher-risk disease who may benefit more from this escalation of care?
  • HERTHENA-Lung01: phase II registrational trial evaluating the HER3-targeting antibody–drug conjugate patritumab deruxtecan (HER3-DXd) in patients with EGFR-mutated advanced NSCLC following progression on an EGFR TKI and platinum-based chemotherapy (abstract OA05.03)
    • Treatment options are scarce for EGFR-mutated advanced NSCLC previously treated with EGFR TKI therapy and platinum-based chemotherapy. In phase I, HER3-DXd showed promising efficacy and manageable safety in this setting—results that will be reinforced by the report of HERTHENA-Lung01 at WCLC 2023, including clinically meaningful activity across various EGFR TKI resistance mechanisms and HER3 expression levels and the first report of its efficacy in the central nervous system. If these data lead to an approval by the FDA, HER3-DXd will become the favored third-line option for EGFR-mutated advanced NSCLC and the only approved targeted therapy post osimertinib.
  • INSIGHT 2: phase II trial evaluating combination therapy with tepotinib, a selective MET inhibitor, plus osimertinib in patients with EGFR-mutated advanced NSCLC and MET amplification following first-line osimertinib (abstract OA21.05)
    • MET amplification is a common resistance mechanism seen at progression on osimertinib in EGFR-mutated NSCLC. At WCLC 2023, the primary analysis from INSIGHT 2 promises to show that adding a MET inhibitor to osimertinib in the setting of MET amplification is efficacious and safe in this subset of patients. Consistent with a precision oncology framework, the results of INSIGHT 2 will help clarify the utility of biopsy and biomarker testing to identify rational second-line targeted therapy approaches in the setting of osimertinib resistance before moving on to platinum-based chemotherapy.

Additional studies of interest include:

  • I-SABR: randomized trial evaluating nivolumab after stereotactic ablative radiotherapy in patients with early-stage NSCLC (abstract OA12.04)
  • AEGEAN: surgical outcomes from a phase III trial evaluating neoadjuvant durvalumab plus chemotherapy followed by adjuvant durvalumab in patients with resectable NSCLC (abstract OA12.05)
  • TRIDENT-1: updated efficacy and safety results with long-term follow-up from a pivotal phase I/II trial evaluating repotrectinib, a next-generation ROS1 TKI, in patients with ROS1 fusion–positive advanced/metastatic NSCLC (abstract OA03.06)
  • FAVOUR: preliminary efficacy and safety results from a phase Ib study evaluating the oral, brain-penetrant, selective EGFR inhibitor furmonertinib in patients with EGFR exon 20 insertion–positive advanced/metastatic NSCLC (abstract OA03.04)
  • CHRYSALIS: updated efficacy and safety results from a phase I study evaluating the EGFR/MET bispecific antibody amivantamab in patients with MET exon 14–positive advanced/metastatic NSCLC (abstract OA21.04)
  • EVOKE-02: preliminary report of a phase II study evaluating combination therapy with the TROP-2–targeting antibody–drug conjugate sacituzumab govitecan plus pembrolizumab in patients with newly diagnosed metastatic NSCLC (abstract OA05.04)
  • TROPION-Lung04: preliminary report of a phase Ib study evaluating the TROP-2–targeting antibody–drug conjugate datopotamab deruxtecan (Dato-DXd) plus durvalumab with or without carboplatin in patients with advanced/metastatic NSCLC (abstract OA05.06)
  • DESTINY-Lung02: primary analysis from a phase II trial evaluating the HER2-targeting antibody–drug conjugate trastuzumab deruxtecan (T-DXd) in patients with HER2-mutated metastatic NSCLC (abstract MA13.10)
  • EMPOWER-Lung 1 and 3: updated exploratory analysis by liver metastases from 2 phase III trials evaluating cemiplimab-based therapy in patients with advanced NSCLC (abstract P2.06-01)
  • LUNAR: subgroup analysis by PD-L1 expression from a phase III trial evaluating tumor-treating field therapy in combination with either docetaxel or immune checkpoint inhibitor therapy for metastatic NSCLC after failure of platinum-based chemotherapy (abstract OA22.05)
  • Subgroup analysis of patients with refractory small-cell lung cancer from a phase I/II study evaluating ifinatamab deruxtecan (DS-7300) in patients with heavily pretreated solid tumors (abstract OA05.05)
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What magnitude of increase in median progression-free survival would you need to see reported for FLAURA2 to consider adding platinum-based chemotherapy to osimertinib for your patients with newly diagnosed EGFR-mutated advanced NSCLC if the potential increase in toxicity were as expected?

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