#AACR16 Update: Checkpoint Inhibition and Improving Anti-Tumor Immunity

Checkpoint inhibitors, which release the immune system’s brakes to strengthen an anti-tumor immune response, are currently the most widely successful class of immunotherapies, benefiting patients with a variety of cancers, including those at very advanced stages of disease. Day two of the 2016 annual meeting of the American Association for Cancer Research highlighted even more of their benefits in cancer patients.

F. Stephen Hodi, M.D, a member of the CVC Trials Network managed by both CRI and Ludwig Cancer Research, showed that nivolumab⎯an antibody that inhibits activity of the PD-1 pathway⎯led to historically high rates of survival in metastatic melanoma patients after five years. Since 2005, only 16.6% of all patients with advanced melanoma survived at least five years, while more than twice as many patients—34%—hit that survival threshold after treatment with nivolumab immunotherapy.

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On the combination immunotherapy front, Michael Postow MD, discussed the benefits of treating advanced melanoma with a combination of nivolumab and ipilimumab⎯an anti-CTLA-4 antibody and the first checkpoint inhibitor to receive FDA approval⎯as opposed to ipilimumab alone. After two years, tumors in patients treated with both checkpoint inhibitors together decreased by 70%, while those treated with ipilimumab alone increased by 5% (though one wonders how much of that growth can be attributed to infiltration of immune cells to the tumor site). Overall, 61% of patients responded to the combination treatment compared to only 11% of those who received ipilimumab alone. Furthermore, durable responses two years out are still seen in 80% of the patients who responded initially to the combination therapy. Combination-treated patients also showed improved rates of progression-free survival (51% vs. 12%) and overall survival (64% vs. 54%) compared to patients who only received ipilimumab. These differences were even more pronounced among patients who lacked the V600 mutation.

Dr. Matteo Carlino presented work involving Dr. Antoni Ribas⎯a member of the CVC Trials Network and a principle investigator on the CRI-SU2C Cancer Immunology Dream Team—showing that tumors expressing PD-L1 (the ligand or counterpart to PD1) were more likely to benefit from anti-PD-1 therapy than tumors that did not. Additionally, higher levels of PD-L1 expression correlated with higher response rates after treatment with pembrolizumab, an anti-PD1 checkpoint inhibitor, but not with ipilimumab, which targets the CTLA-4 pathway. The six-month progression-free survival rates of patients with PD-L1-positive tumors were 51% and 25%, respectively, in response to pembrolizumab and ipilimumab treatments. On the bright side, even patients whose tumors lacked PD-L1 still showed responses to both pembrolizumab and ipilimumab monotherapies, which led to progression-free survival rates of 32% and 28%, respectively.

Coming up next on our report from #AACR16, we’ll share latest reports on the role of the tumor microenvironment in cancer.