However, durvalumab might help fill a treatment gap for post-chemoradiotherapy consolidation, especially when no consolidation chemotherapy is planned.

“The PACIFIC study is the highest hope for durvalumab right now,” Dr Tanvetyanon continued. “In the setting of post-radiotherapy to the lung, there is a greater concern for safety if a complication like pneumonitis were to happen. At this time there is really no approved consolidation therapy (except chemotherapy carboplatin/paclitaxel for patients who received concurrent carboplatin/paclitaxel with radiotherapy) so durvalumab will potentially fill this gap very nicely if the FDA approves it.”


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Combining immune checkpoint inhibitors with different targets like PD-1/PD-L1 and CTLA-4, might offer better lung tumor response rates than single-target checkpoint blockade, Dr Tanvetyanon and others have argued—but such combinations appear to entail increased toxicity than single-agent immune checkpoint inhibition.9

“I am cautiously optimistic for the future development of durvalumab given the strength of the AstraZeneca drug pipeline, which includes a range of different partners for the development of rational combinations, which could be very relevant for NSCLC and other cancers,” said Timothy Yap, MD PhD, a medical oncologist and associate professor  in the Departments of Investigational Cancer Therapeutics and Thoracic/Head and Neck Medical Oncology, a MD Anderson Cancer Center in Houston, Texas. “Nevertheless, appropriate patient selection through the use of analytically validated predictive biomarkers and other strategies will be key to its ultimate success.”

Patient selection for durvalumab is likely to remain a challenge, as well, because although PD-L1 expression is prognostic, indicating poor prognosis, it does not appear to be a robust predictive biomarker for tumor response to durvalumab treatment; better biomarkers are needed.3-5,10 Tobacco smoking status might also affect PD-L1 expression and durvalumab outcomes in lung cancer. Lung tumor PD-L1 overexpression is more frequently observed in men and tobacco smokers.10 Patients who have never smoked showed no clinical response, regardless of tumor lung tumor histology or PD-L1 expression.1

“The next steps are to better understand how to predict the efficacy of and resistance to these new immunotherapy-based strategies and how to address primary and secondary resistance,” noted Arnaud Jeanson and Fabrice Barlesi in a recent review.5

References

  1. Ogunleye F, Blankenship L, Millisor V, et al. Programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors, heralding a new era of immunotherapy in the management of advanced non-small cell lung cancer (NSCLC). Cancer Treat Res Commun. 2017;12:6-13. doi: 10.1016/j.ctarc.2017.05.002
  2. Khanna P, Blais N, Gaudreu PO, Corrales-Rodriguez L. Immunotherapy comes of age in lung cancer. Clin Lung Cancer. 2016;18(1):13-22. doi: 10.1016/j.clic.2016.06.006
  3. Califano R, Kerr K, Morgan RD, et al. Immune checkpoint blockade: a new era for non-small cell lung cancer. Curr Oncol Rep. 2016;18(9):59. doi: 10.1007/s11912-016-0544-7
  4. Kumar R, Collins D, McDonald F, et al. Targeting the PD-1/PD-L1 axis in non-small cell lung cancer. Curr Probl Cancer. 2017;41:111-124. doi: 10.1016/j.currproblcancer.2016.12.002
  5. Jeanson A, Barlesi F. MEDI 4736 (durvalumab) in non-small cell lung cancer. Exp Opin Biol Ther. 2017 July 13. doi: 10.1080/14712598.2017.1351939 [Epub ahead of print].
  6. Antonia S, Goldberg SB, Balmanoukian A, et al. Safety and antitumor activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016;17:299-308. doi: 10.1016/S1470-2045(15)00544-6
  7. Makarious D, Horwood K, Coward JIG. Myasthenia gravis: an emerging toxicity of immune checkpoint inhibitors. Eur J Cancer. 2017;82:128-136. doi: 10.1016/j.ejca.2017.05.041
  8. Carrera W, Baartman BJ, Kosmorsky G. A case report of drug-induced myopathy involving extraocular muscles after combining therapy with tremelimumab and durvalumab for non-small cell lung cancer. Neuro-ophthalmol. 2017;41(3):140-143. doi: 10.1080/01658107.2017.1291686
  9. Tanvetyanon T, Gray JE, Antonia SJ. PD-1 checkpoint blockade alone or combined with PD-1 and CTLA-4 blockade as immunotherapy for lung cancer? Exp Opin Biol Ther. 2017 January 18. [Epub ahead of print]. doi: 10.1080/14712598.2017.1280454
  10. Wu S, Shi X, Sun J, et al. The significance of programmed cell death ligand 1 expression in resected lung adenocarcinoma. Oncotarget. 2017;8(10):16421-16429. doi: 10.18632/oncotarget.14851