A recent study showed that among melanoma patients treated with the PD-1 inhibitor MK-3475, those whose tumors had the protein PD-L1 had better immune responses and higher survival rates. The results were presented at the Annual Meeting of the American Association for Cancer Research (AACR), being held in SanDiego, April 5-9, 2014.
The researchers foundthat when the protein PD-L1, which is present on some melanoma tumors, binds to PD-1, a protein present on T cells, ?brakes? are applied on these T cells, preventing them from attacking the cancer cells. The immunotherapy MK-3475 blocks PD-1, releasing the brakes on T cells and enabling them to attack the cancer cells.
In this study, the researchersfurther mote that among melanoma patients who received MK-3475, those whose tumors had PD-L1 had an overall response rate of 46%, while those whose tumors did not have PD-L1 had an overall response rate of 17%. At six months, 64% of the patients whose tumors were PD-L1-positive had no disease progression, compared with 34% of those whose tumors were PD-L1-negative. Similarly, 86% of the patients whose tumors were PD-L1-positive were alive after one year, compared with 72% of those whose tumors were PD-L1-negative.
This is the largest data set ever looking at PD-L1 expression in tumors from melanoma patients treated with PD-1 inhibitors
?We found a major difference in the response rates between patients with PD-L1-positive and PD-L1-negative tumors treated with MK-3475,? saidAdil I. Daud, M.D., co-director of theUCSF Melanoma Center, and director of melanoma clinical research at theUCSF Helen Diller Family Comprehensive Cancer Center. ?This is the largest data set yet, to my knowledge, looking at PD-L1 expression in tumors from melanoma patients treated with PD-1 inhibitors.”
Which patient benefits.
?Data from this study identifies PD-L1 as a robust marker in determining which melanoma patients may be well served when treated with MK-3475. However, we are studying more samples from randomized trials of PD-1 inhibitor versus ipilimumab or chemotherapy to establish the validity of this marker,? Daud added
To evaluate the relationship between tumor PD-L1 expression and clinical outcome, Daud and colleagues studied tumor samples collected from 195 patients recruited to a phase I clinical trial testing MK-3475 at three different doses. All patients had late-stage melanoma, and some of them had received prior treatment with another immunotherapy drug called ipilimumab (Yervoy?, Bristol-Myers Squibb Company)
The investigators measured the amounts of PD-L1 in the tumor samples and considered them PD-L1-positive if at least one cell per 100 tumor cells had the protein. They found that, of the 125 evaluable tumor samples, 89 were PD-L1-positive and 36 were PD-L1-negative.Patients with PD-L1-positive tumors had disease that did not progress for about 50 weeks, while disease progressed at about 12 weeks for those with PD-L1-negative tumors.
Response rate
The investigators also found that among patients whose tumors were PD-L1-positive, overall response rates between those who had and had not received prior therapy with ipilimumab (44% versus 47% ) were not significantly different. Similarly, among patients whose tumors were PD-L1-negative, overall response rates between those who had and had not received prior therapy with ipilimumab (14% versus 17%) were not significantly different. ?This suggests that prior treatment with the anti-CTLA-4 antibody ipilimumab does not impact the ability of these tumors to respond to MK-3475, nor does it affect the viability of PD-L1 as a marker of response to MK-3475,? Daud noted
The investigators found a 24% and 17.5% increase in two types of activated T cells, CD8-positive and CD4-positive T cells, in the blood of patients treated at three different doses of MK-3475 for six weeks, leading them to suggest that the treatment improved the immune response in these patients at all doses tested.
For more information
Study of MK-3475 in Participants With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, or Non-small Cell Lung Carcinoma (P07990/MK-3475-001/NCT01295827).Study Record Detail.
Disclosure: This study was funded by Merck. Daud has served on the advisory boards of Merck and GlaxoSmithKline PLC.Photo:Adil I. Daud, M.D.,Photo Courtesy:The University of California, San Francisco, CA 94143, 415/476-9000.
Copyright ? 2014 InPress Media Group/Sunvalley Communication. All rights reserved. Republication or redistribution of InPress Media Group/Sunvalley Communication content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group/Sunvalley Communication. InPress Media Group/Sunvalley Communication shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Onco’Zine and Oncozine are registered trademarks and trademarks of Sunvalley Communication around the world.
