Non-Small Cell Lung Cancer: RT Out, Pembrolizumab In, and Vaccine Hope or Hype

Three articles on non-small cell lung cancer (NSCLC) recently appeared which were of interest and might alter therapy. The first on whole brain radiation therapy (WBRT) was presented at the at the European Respiratory Society (ERS) International Congress 2016 and simultaneously published online in the Lancet (1). WBRT and dexamethasone have been the standard of care for patients with NSCLC brain metastases. However, the study of 538 randomized patients concludes that WBRT provides "little additional clinically significant benefit" with brain metastases. Notably, all the patients were unsuitable for surgical resection or stereotactic radiotherapy, owing to widespread metastases. However, patients younger than 60 years did seem to have a survival advantage and might represent an exception.

The second study presented at the European Society for Medical Oncology (ESMO) 2016 Congress reports that the addition of pembrolizumab to first-line treatment with pemetrexed and carboplatin significantly improved objective response rate and progression-free survival in NSCLC (2). The study included 123 treatment-naive NSCLC patients whose tumors did not harbor EGFR or ALK aberrations. Participants were randomly assigned to receive pemetrexed plus carboplatin with or without pembrolizumab. At a median follow-up of 10.6 months, results showed that objective response rate was 55% with pembrolizumab vs 29% with chemotherapy alone (treatment difference, 26%; 95% CI, 9-42; P = .0016). All responses were partial.

Pembrolizumab is a humanized IgG4 monoclonal antibody (mouse antibody grafted to human immunoglublin) which destroys a protective mechanism on cancer cells, allowing the immune system to destroy those cancer cells. It targets the programmed cell death 1 (PD-1) receptor. The drug was initially used in treating metastatic melanoma but is a promising new therapy for advanced cancers, now including lung cancer. Brighton et al. (3) recently reported in the SWJPCC that pembrolizumab can result in drug-induced pneumonitis.

Earlier this spring a Fox News report in Phoenix made some spectacular claims about a Cuban lung cancer vaccine concluding that it “could literally save millions of live” (4-includes a video of the original broadcast). Dr. Santosh Rao from Banner MD Anderson Cancer Center in Phoenix, who apparently has seen studies on the vaccine says that the vaccine does something, and that it extends life. However, he added that "the question will always come up, is it better than some of the new therapies that we have that also help the immune system function better". Banner MD Anderson Cancer Center has been promoting the coverage on social media adding that the vaccine is “potentially groundbreaking". Dr. Doug Campos-Outcalt, Chair of New Department of Family, Community and Preventive Medicine, commented that he was as baffled by the coverage. “Why MD Anderson would hype this alleged breakthrough before it has undergone controlled clinical trials is beyond my understanding,” said Campos-Outcalt. The drug has not been used in the United States but Roswell Park Institute in Buffalo, NY, has applied to do a clinical trial on the vaccine called CIMAVax. If approved, the trial will probably not begin until 2017 and will likely take several years.

Richard A. Robbins, MD

Editor, SWJPCC

References

1. Mulvenna P, Nankivell M, Barton R, et al. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet. 2016 Oct 22;388(10055):2004-14. [CrossRef] [PubMed]
2. Hoffman J. Adding pembrolizumab to chemo improves efficacy in metastatic NSCLC. Cancer Therapy Advisor. November 1, 2016. Available at: http://www.cancertherapyadvisor.com/lung-cancer/lung-cancer-nsclc-pembrolizumab-chemotherapy-improved-efficacy/article/569669/ (accessed 11/2/16).
3. Brighton AM, Jain T, Bryce AH, Sista RR, Viggiano RW, Wesselius LJ. November 2016 pulmonary case of the month. Southwest J Pulm Crit Care. 2016:13(5):191-5. [CrossRef]
4. Lomangino K. FOX, Banner MD Anderson hype Cuba cancer “breakthrough”. Health News Review. March 7, 2016. Available at: http://www.healthnewsreview.org/2016/03/fox-md-anderson-hype-cuba-cancer-breakthrough-rumors/ (accessed 11/2/16).

Cite as: Robbins RA. Non-small cell lung cancer: RT out, pembrolizumab in, and vaccine hope or hype. Southwest J Pulm Crit Care. 2016;13(5):205-6. doi: http://dx.doi.org/10.13175/swjpcc107-16 PDF

Comments

[Rick Robbins, M.D.]

On 11/4 the US Food and Drug Administration approved the Roswell Park Cancer Institute in Buffalo clinical trial of the lung cancer vaccine CIMAvax. The newly approved study will be phase 1/2 trial of CIMAvax in combination with the anti-PD1 checkpoint inhibitor nivolumab (Opdivo, Bristol-Myers Squibb) in patients previously treated for advanced NSCLC. Roswell Park anticipates that the trial will take 3 years to complete and will enroll 60 to 90 patients.

[Rick Robbins, M.D.]

The Miami Herald (http://www.miamiherald.com/news/nation-world/world/americas/cuba/article155129444.html) is reporting that the first patients in a clinical trial at Roswell Park Cancer Institute have begun receiving monthly doses of CIMAvax-EGF. CIMAvax-EGF is a Cuban lung cancer vaccine that some researchers say shows promise in preventing the recurrence of lung cancer. The Roswell trial, which was authorized by the U.S. Food and Drug Administration last fall, is the first time that a Cuban-made therapy has been tested on U.S. patients.