In conclusion, immunotherapy has demonstrated a significant survival benefit in patients with advanced NSCLC. Recent studies combining chemotherapy and checkpoint inhibition have demonstrated OS benefits in the first-line setting. This combination has become standard of care for patients with advanced NSCLC (Figure 1). The excitement surrounding immunotherapy and checkpoint inhibition stems from the durable responses that are observed in some patients with advanced NSCLC. Given these results, understanding how to improve responses and outcomes in patients with advanced NSCLC will be extremely important given the potential for durable responses with immunotherapy. Additional research is needed to further our understanding of the biology underlying those patients that are “exceptional-responders” to immunotherapy.
It will also be important to understand more fully how to incorporate immunotherapy with chemotherapy to improve patient outcomes not only in advanced staged lung cancers but also in early stage disease as well. Already, durvalumab is FDA approved for patients with unresectable, stage III NSCLC. Other studies have explored the use of immunotherapy in the adjuvant setting in patients with early stage NSCLC with results pending.41 Neoadjuvant immunotherapy is also being studied in early stage NSCLC. A pilot study using neoadjuvant nivolumab in patients with early stage NSCLC demonstrated a 43% response rate as determined by major pathologic response at time of surgery.41–43 More recently a phase I study is underway testing pembrolizumab for Stage I and II NSCLC in the neoadjuvant setting and has demonstrated promising results.44
It should also be noted that several studies included EGFR-positive patients with advanced NSCLC and a recent meta-analysis was completed to assess outcomes in these patients.45 As mentioned previously the CheckMate 057 trial assessed the use of nivolumab vs docetaxel in the second-line setting for treatment of advanced NSCLC. Approximately 14% of patient enrolled were EGFR-positive median OS was 12.2 vs 9.4 months in patients treated with nivolumab vs docetaxel, however, this was not statistically significant (HR: 1.18; 95%CI: 0.69–2.00).46 Pembrolizumab has also been assessed in EGFR-positive patients. The KEYNOTE-010 as previously mentioned was a study assessing previously treated patients with advanced NSCLC randomized to pembrolizumab (2 mg/kg and 10 mg/kg) vs docetaxel. Patients treated with either dose of pembrolizumab demonstrated improve OS as compared to docetaxel, however, this was statistically significant (HR: 0.88; 95%CI: 0.45–1.70). Finally, two studies using atezolizumab in the second-line setting for treatment of patients with advanced NSCLC have included EGFR-positive patients. Both these studies failed to demonstrate a significant improvement in OS.13,47 Further studies are needed to assess whether combination or sequential immunotherapy and EGFR tyrosine kinase inhibitor (standard of care for EGFR-positive advanced stage NSCLC) treatment will lead to better outcomes in EGFR-positive patients. Altogether, understanding how to optimize the benefits of immunotherapy for patients with NSCLC will be extremely important in improving patient outcomes.
Dr Shirish Gadgeel reports personal fees from Genentech/Roche, Astra-Zeneca and Takeda. The authors report no other conflicts of interest in this work.
Frank Weinberg, Shirish Gadgeel
Division of Hematology and Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI, USA
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Source: Lung Cancer: Targets and Therapy.
Originally published June 4, 2019.
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