Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer

Jatin Patel, Mercer University College of Pharmacy

Lung cancer is divided into two main histopathologic subtypes: non-small cell and small cell. According to Basic & Clinical Pharmacology, non-small cell lung cancer (NSCLC) makes up about 80% of all cases of lung cancer which includes adenocarcinoma, squamous cell cancer, and large cell cancer.1 Currently, 75% to 85% of lung cancer cases are caused by cigarette smoking and the main factor responsible for smoking dependence is nicotine according to Casarett and Doull’s Toxicology: The Basic Science.2

National Comprehensive Cancer Network (NCCN) Guidelines suggest that Taxotere® (docetaxel) can be used as a first line therapy agent in patients who have NSCLC. In addition, most new agents for the treatment of NSCLC are not indicated for this subtype because of their toxicity or lack of efficacy or because their activity is limited to tumors with specific genetic alterations that are rarely found in squamous-cell NSCLC. Furthermore, the NCCN Guidelines does not make any recommendation in regards to Opdivo® (nivolumab) in the treatment of NSCLC.3

Title: Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer4
Design Randomized, open-label, international, phase 3 study; N=352
Objective To evaluated the efficacy and safety of nivolumab as compared with docetaxel
Study Groups Nivolumab group and docetaxel group
Methods The study randomized 272 patients; 135 patients were randomly assigned to receive nivolumab, at a dose of 3 mg per kilogram of body weight every 2 weeks, and 137 were randomly assigned to receive docetaxel, at a dose of 75 mg per square meter of body-surface area every 3 weeks. Both drugs were administered intravenously. Patients were treated until the disease progressed or discontinued the treatment due to toxic effects or other reasons.
Duration October 2012 through December 2013
Primary Outcome Measure Overall survival
Baseline Characteristics Nivolumab (n=135) Docetaxel (n=137)
Age range – years 39-85 42-84
Sex – Male 82% 71%
Race – White 90% 95%
Other systemic cancer therapy
Gemcitabine 44% 52%
Paclitaxel 34% 34%
Vinorelbine 15% 18%
Etoposide 13% 8%
Results The median overall survival was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) in the nivolumab group versus 6.0 months (95% CI, 5.1 to 7.3) in the docetaxel group. Overall survival was significantly longer with nivolumab than with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P<0.001). At 1 year, the overall survival rate was 42% (95% CI, 34 to 50) with nivolumab versus 24% (95% CI, 17 to 31) with docetaxel. The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel (hazard ratio for death or disease progression, 0.62; 95% CI, 0.47 to 0.81; P<0.001).
Adverse Events Common Adverse Events:
Nivolumab (n=131) Docetaxel (n=129)
Fatigue 17% 41%
Decreased appetite 12% 20%
Asthenia 10% 18%
Nausea 9% 25%
Diarrhea 8% 22%
Anemia 2% 25%
Alopecia 0% 23%
Serious Adverse Events:
Pyrexia 2% 2%
Pneumonitis 3% 0%
Febrile neutropenia 0% 20%
Neutropenia 0% 6%
Percentage that Discontinued due to Adverse Events: nivolumab group (3%) and docetaxel group (10%).
Study Author Conclusions Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level.

The study showed superior survival and an improved safety profile with nivolumab versus standard-of-care docetaxel in patient with advanced, previously treated squamous-cell NSCLC. The frequencies of both hematologic and nonhematologic adverse events, including severe toxic events, were substantially less with nivolumab than with docetaxel, as were adverse events leading to discontinuation. Further research is needed to identify relevant biomarkers that have sufficient sensitivity and specificity to predict which patients are most likely to benefit.

References

  1. Chu E, Sartorelli AC. Cancer Chemotherapy. In: Katzung BG, Trevor AJ. Basic & Clinical Pharmacology, 13e. New York, NY: McGraw-Hill; 2015. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1193&Sectionid=69112486. Accessed July 13, 2015.
  2. Leikauf GD. Toxic Responses of the Respiratory System. In: Klaassen CD. Casarett and Doull’s Toxicology: The Basic Science of Poisons, Eighth Edition. New York, NY: McGraw-Hill; 2013. http://accesspharmacy.mhmedical.com/content.aspx?bookid=958&Sectionid=5348373. Accessed July 13, 2015.
  3. National Comprehensive Cancer Network (NCCN). Non-Small Cell Lung Cancer Guidelines, Version 3. 2014. Available at: http://www.tri-kobe.org/nccn/guideline/lung/english/non_small. Accessed July 13, 2015.
  4. 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(2):123-35.
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