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  IBS24 - Optimal Immunotherapy Sequence in Stage IV NSCLC (Ticketed Session) (ID 55)

  • Event: WCLC 2019
  • Type: Interactive Breakfast Session
  • Track: Immuno-oncology
  • Presentations: 1
  • Now Available
  • Moderators:
  • Coordinates: 9/10/2019, 07:00 - 08:00, Interlaken (1988)

  • 29501

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    IBS24.02 - IO Followed by Chemo or Chemo Followed by IO (Now Available) (ID 3390)

    07:00 - 08:00  |  Presenting Author(s): Barbara Melosky
    • Abstract
    • Presentation
    • Slides

    Abstract
    

    IBS24 - Optimal Immunotherapy Sequence in Stage IV NSCLC

    Barbara Melosky

    Immunotherapy Followed by Chemotherapy or Chemotherapy Followed by Immunotherapy

    For our patients presenting with stage IV advanced NSCLC, the goals of therapy are primarily palliative. These goals need to be carefully balanced to meet the individual needs of each patient: while we want to keep our patients living as long as possible, we also want to provide them with the highest quality of life. Many patients with advanced NSCLC are treated with the combination of immunotherapy and chemotherapy. This comes at a cost of toxicity and may not be the best strategy for long term survival. We need to compare the evidence to determine which agent, immunotherapy or chemotherapy, to use first in patients with stage IV advanced NSCLC without a targetable mutation (wild-type).

    Immunotherapy followed by Chemotherapy

    Numerous phase III trials have compared immunotherapy to chemotherapy for patients with stage IV NSCLC. Some of the trials to be discussed include KEYNOTE 024¹, KEYNOTE 189², KEYNOTE 407³, KEYNOTE 042⁴, CheckMate 227⁵ and MYSTIC⁶. For each trial, the outcomes and side effect profiles will be presented, and the different trials will be compared.

    OR

    Chemotherapy followed by Immunotherapy

    Immunotherapy agents were initially studied after patients progressed on a platinum doublet. Trials to be discussed include CheckMate 017⁷ (squamous), CheckMate 057⁸ (non-squamous), KEYNOTE 010⁹, and OAK¹⁰. Again, outcomes and side effect profiles will be presented with a view to identifying which patients will experience the greatest benefit from this strategy.

    Conclusion & Key Points

    The increasing percentage of long term survivors in lung cancer is unprecedented and strengthens the argument that sequencing is important.

    While the evidence is clear that immunotherapy is the best choice for patients who express high PD-L1 or have high tumour mutational burden (TMB), evidence is less clear for how to treat patients without these biomarkers.

    	IO followed by Chemo	Chemo followed by IO
    Biomarkers	PD-L1 expression, high TMB	PD-L1 non-expressors, low TMB, non-selected population
    Evidence to support	KEYNOTE 024//042, CheckMate 227, MYSTIC	CheckMate 017/057, KEYNOTE 010, OAK

    References

    1. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. J Clin Oncol 2019; 37:537.

    2. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med 2018; 378:2078.

    3. Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med 2018; 379:2040.

    4. Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 2019.

    5. Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N Engl J Med 2018; 378:2093.

    6. Peters S, Cho BC, Reinmuth N, et al. Tumor mutational burden (TMB) as a biomarker of survival in metastatic non-small cell lung cancer (mNSCLC): Blood and tissue TMB analysis from MYSTIC, a Phase III study of first-line durvalumab ± tremelimumab vs chemotherapy. AACR 2019; #CT074.

    7. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med 2015; 373:123.

    8. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med 2015; 373:1627.

    9. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomized controlled trial. Lancet 2016; 387:1540.

    10, Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 2017; 389:255.

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