Anti-PD-1 Therapy Versus Chemotherapy for NSCLC Treatment

Ling Jun Chen, Mercer University College of Pharmacy

Non-small cell lung cancer (NSCLC) and small cell lung cancer are two distinct types of lung cancer.  Between 80 and 85% of lung cancers have been determined to be NSCLC.  This cancer has been classified as expressing a high concentration of programmed death ligand 1 (PD-L1) in approximately 25% of patients. [1] 

This transmembrane protein, PD-L1, plays a role in suppressing the immune system.  Keytruda® (pembrolizumab) is a programmed death receptor-1 blocking antibody. [2]  Until this trial, treatment for lung cancer has been limited to cytotoxic chemotherapy.

Pembrolizumab versus chemotherapy for PD-L1-positive NSCLC [3]
Design International, randomized, open-label, intention-to-treat; N= 305
Objective To compare pembrolizumab with chemotherapy as first-line NSCLC therapy
Study Groups Pembrolizumab group (n= 154); chemotherapy group (n= 151)
Methods Patients with advanced NSCLC and a PD-L1 tumor proportion score of 50% or greater were randomly assigned to receive pembrolizumab 200 mg intravenously every 3 weeks for 35 cycles or the investigator’s choice of platinum-based chemotherapy regimens for 4 to 6 cycles.
Duration (Range) September 19, 2014 to October 29, 2015
Primary Outcome Measure Progression-free survival
Baseline Characteristics Pembrolizumab Chemotherapy
Mean age, years 64.5 66.0
Male, n (%) 92 (59.7) 95 (62.9)
Enrollment from East Asia, n (%) 21 (13.6) 19 (12.6)
Enrollment from non-East Asia, n (%) 133 (86.4) 132 (87.4)
Smoking status, n (%)
Current 34 (22.1) 31 (20.5)
Former 115 (74.7) 101 (66.9)
Never 5 (3.2) 19 (12.6)
Histology, n (%)
Squamous 29 (18.8) 27 (17.9)
Nonsquamous 125 (81.2) 124 (82.1)
Results Pembrolizumab Chemotherapy
Median progression-free survival, months (95% CI) 10.3 (95% CI, 6.7 to not reached) 6.0 (95% CI, 4.2 to 6.2)
Alive and no disease progression at 6 months 61% (95% CI, 53.8 to 69.4) 50.3% (95% CI, 41.9 to 58.2)
Progression-free survival was longer in the pembrolizumab group (p= 0.005). The hazard ratio for disease progression or death was 0.60 (95% CI, 0.41-0.89).
Adverse Events Pembrolizumab (%) Chemotherapy (%)
Any, n 113 (73.4) 135 (90.0)
Serious, n 33 (21.4) 31 (20.7)
Led to discontinuation, n (%) 11 (7.1) 16 (10.7)
Led to death, n (%) 1 (0.6) 3 (2.0)
Nausea, n (%) 15 (9.7) 65 (43.3)
Anemia, n (%) 8 (5.2) 66 (44.0)
Fatigue, n (%) 16 (10.4) 43 (28.7)
Diarrhea, n (%) 22 (14.3) 20 (13.3)
Any immune-mediated, n (%) 45 (29.2) 7 (4.7)
Hypothyroidism, n (%) 14 (9.1) 2 (1.3)
Hyperthyroidism, n (%) 12 (7.8) 2 (1.3)
Severe skin reaction, n (%) 6 (3.9) 0 (0)
Study Author Conclusion Pembrolizumab was associated with longer progression-free and overall survival and fewer treatment-related adverse events than platinum-based combination chemotherapy.

With an extra five months of progression-free survival, pembrolizumab has the potential to change the management of NSCLC in patients with a PD-L1 tumor proportion score of 50% or greater.  The endpoints of tolerability were also more favorable to pembrolizumab.  One limitation of this trial is that patients with lower tumor proportion scores were not assessed.  Another limitation is that pembrolizumab was administered at a fixed dose instead of patient-specific doses.  Future trials should consider how the combination of pembrolizumab and chemotherapy could jointly treat NSCLC.  

References:

  1. Lung Cancer. American Cancer Society. 2016. Available at: http://www.cancer.org/cancer/lungcancer/. Accessed October 17, 2016.
  2. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2016;387:1540-1550.
  3. Reck M, Rodríguez-abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016.
Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s