The Immune Checkpoint Inhibitor Pembrolizumab (Keytruda) Is Effective in 13 Cancer Types
We continue our second article titled "The Shining Three Musketeers of Cancer Treatment" with pembrolizumab (Aramis). Pembrolizumab, one of the drugs that removes the immune system's braking mechanisms, was found effective and approved by the FDA (American Food and Drug Administration) for advanced malignant melanoma (skin cancer) in September 2014 last year, like its two companions ipilimumab and nivolumab.
The most important characteristic of these drugs, which can reactivate the knocked-out immune system in a cancer patient, was that they were not specific to a cancer type. The possibility that they might be effective in many cancers besides skin and lung cancer therefore left the entire oncology community eagerly waiting. At ASCO (the cancer congress attended by the largest number of physicians in the world, held in Chicago at the end of May each year) 2015, preliminary results of pembrolizumab studies in various cancers were announced. Almost all preliminary results for pembrolizumab tested in different cancers were welcomed with joy on behalf of our patients and the oncology community.
How Pembrolizumab Fights Cancer: PD-1, also known as programmed cell death protein, is a receptor on the surface of immune cells. Protein ligands called PD-L1 and PD-L2 released by cancer cells bind to this receptor and activate the immune system's braking mechanism against cancer. Pembrolizumab binds to these protein structures and prevents this braking mechanism from working. The freed immune cells act to recognize and destroy cancer (figure).
The main cancer types in which pembrolizumab activity has been observed are metastatic malignant melanoma, head and neck cancer, small cell lung cancer, esophageal cancer, stomach cancer, bladder cancer, non-small cell lung cancers, liver cancer (hepatocellular cancer), ovarian cancer (the ovaries in women), and colon and rectal (large bowel) cancer.
The data on the drug's effectiveness in all these diseases are still preliminary results. They are not currently sufficient to change the treatment strategies we use. Data from ASCO 2015 allow us to look to the future with hope and indicate that new strategies will be added to the many successful treatments currently used to fight cancer. We will eagerly await the publication of comprehensive data from these studies in the coming period.
In my opinion, ipilimumab, nivolumab, and pembrolizumab deserve to be called the three musketeers of the modern age for making a difference in malignant melanoma, one of the cancers that challenges us most in oncology treatment, and initiating a fight that will make a difference against many other cancers.
For animations and videos on this topic, click here.
Sources
1. (Abstract #LBA6008) Late-Breaker Presentation: Antitumor activity and safety of pembrolizumab in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN): Preliminary results from KEYNOTE-012 expansion cohort. T. Seiwert. Monday, June 1, 3:39 PM – 3:51 PM CDT. Location: S100bc. ASCO Press Program, Friday, May 29, 1:00 PM CDT.
2. (Abstract #6017) Poster Discussion: Inflamed-phenotype gene expression signatures to predict benefit from the anti-PD-1 antibody pembrolizumab in PD-L1+ head and neck cancer patients. T. Seiwert. Saturday, May 30, 1:15 PM – 4:45 PM CDT (poster session). Location: S Hall A. 4:45 PM – 6:00 PM CDT (discussion). Location: S406.
3. (Abstract #9005) Oral Presentation: Long-term efficacy of pembrolizumab (pembro; MK-3475) in a pooled analysis of 655 patients (pts) with advanced melanoma (MEL) enrolled in KEYNOTE-001. A. Daud. Saturday, May 30, 2:39 PM – 2:51 PM CDT. Location: E354b.
4. (Abstract #3000) Oral Presentation: Atypical patterns of response in patients (pts) with metastatic melanoma treated with pembrolizumab (MK-3475) in KEYNOTE-001. J. Wolchok. Monday, June 1, 1:15 PM – 1:27 PM CDT. Location: S406.
5. (Abstract #3001) Oral Presentation: Association of response to programmed death receptor 1 (PD-1) blockade with pembrolizumab (MK-3475) with an interferon-inflammatory immune gene signature. A. Ribas. Monday, June 1, 1:27 PM – 1:39 PM CDT. Location: S406.
6. (Abstract #3009) Poster Discussion: Pembrolizumab (MK-3475) plus low-dose ipilimumab (IPI) in patients (pts) with advanced melanoma (MEL) or renal cell carcinoma (RCC): Data from the KEYNOTE-029 phase 1 study. M. Atkins. Saturday, May 30, 8:00 AM – 11:30 AM CDT (poster session). Location: S Hall A. 3:00 PM – 4:15 PM CDT (discussion). Location: S406.
7. (Abstract #8011) Clinical Science Symposium: Phase I study of pembrolizumab (pembro; MK-3475) plus ipilimumab (IPI) as second-line therapy for advanced non-small cell lung cancer (NSCLC): KEYNOTE-021 cohort D. A. Patnaik. Sunday, May 31, 4:54 PM – 5:06 PM CDT. Location: E Hall D1.
8. (Abstract #7502) Oral Presentation: Pembrolizumab (MK-3475) in patients (pts) with extensive-stage small cell lung cancer (SCLC): Preliminary safety and efficacy results from KEYNOTE-028. P. Ott. Saturday, May 30, 3:48 PM – 4:00 PM CDT. Location: E Hall D1.
9. (Abstract #LBA100) Late-Breaker Presentation: PD-1 blockade in tumors with mismatch repair deficiency. D. Le. Saturday, May 30, 8:05 AM – 8:17 AM CDT. Location: E Hall D1. ASCO Press Program, Friday, May 29, 1:00 PM CDT.
10. (Abstract #4001) Oral Presentation: Relationship between PD-L1 expression and clinical outcomes in patients with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) in KEYNOTE-012. Y. Bang. Sunday, May 31, 8:12 AM – 8:24 AM CDT. Location: E Hall D2.
11. (Abstract #4010) Clinical Science Symposium: Pembrolizumab (MK-3475) for patients (pts) with advanced esophageal carcinoma: Preliminary results from KEYNOTE-028. T. Doi. Sunday, May 31, 4:54 PM – 5:06 PM CDT. Location: E Hall D2.
12. (Abstract #4502) Oral Presentation: Pembrolizumab (MK-3475) for advanced urothelial cancer: Updated results and biomarker analysis from KEYNOTE-012. E. Plimack. Monday, June 1, 10:09 AM – 10:21 AM CDT. Location: E Arie Crown Theater.
13. (Abstract #5510) Clinical Science Symposium: Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: Interim results from a phase Ib study. A. Varga. Monday, June 1, 3:12 PM – 3:24 PM CDT. Location: E354b.
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