Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Cochrane on Vaccine-Based Immunotherapy for NSCLC

Cochrane; 2017 Dec 16; Zhu, Li, Tiselius, et al

Adding vaccine-based immunotherapy does not appear to offer a survival benefit to conventional curative surgery or radiotherapy for patients with localized stage I to III non-small cell lung cancer (NSCLC), according to a Cochrane review of 9 randomized trials involving nearly 5,000 individuals. Among the findings:

  • Giving vaccine-based immunotherapy after surgery or radiotherapy did not extend life.
  • It was uncertain if immunotherapy improved quality of life, but it did appear to cause more side effects.


Zhu J, Li R, Tiselius E, et al. Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent. Cochrane Database of Syst Rev. 2017, Issue 12. Art. No.: CD011300. doi:10.1002/14651858.CD011300.pub2.


The FLAURA study reported in The New England Journal of Medicine is practice changing for patients with EGFR-mutated non small cell lung cancer and establishes osimertinib as the preferred first-line agent for these patients. The study included 556 previously-untreated patients with EGFR mutated (exon 19 deletions or L858R mutations) advanced non small cell lung cancer and randomized them to received either osimertinib (80 mg daily) or a standard EGFR tyrosine kinase inhibitor (gefitinib or erlotinib). Afatinib was not included as, per the investigators, it was “not widely used and had not been made available as a global standard-of-care EGFR-TKI.” Patients with CNS metastases whose condition was neurologically stable were eligible. The primary end point of the study was the duration of progression free survival.

The osimertinib arm achieved a superior progression free survival at 18.9 months compared to 10.2 months in the standard arm. A benefit was seen regardless of mutation type. Events of CNS progression were observed in 6% of the patients treated with osimertinib versus 15% for patients on standard EGFR TKI’s. With respect to objective response rate, osimertinib had an 80% response rate compared to 76% in the standard group. The median duration of response was longer in the osimertinib group, 17.2 months versus 8.5 months. At the time of data cutoff, the median overall survival could not be calculated in either group. However, there was an “initial signal” of a potential survival benefit with osimertinib with a hazard ratio of death of 0.63. The osimertinib group also had fewer adverse events of grade 3 or higher, 34% versus 45%. Not surprisingly given this category of drug, the most commonly reported adverse events were rash/acne, diarrhea, and dry skin. However, changes in QT interval were reported in a higher percentage of patients in the osimertinib group, 10%, versus 5% in the standard EGFR TKI group.

Given its superior progression free survival benefit and safety profile, osimertinib jumps to the front of the pack for first line EGFR directed therapy. As a result of this trial, osimertinib received breakthrough therapy designation for first-line treatment of patients with advanced EGFR mutation-positive non small cell lung cancers.

—Bobby Daly, MD, MBA

Memorial Sloan-Kettering Cancer Center

Bobby Daly, MD, MBA