Relevant clinical trials, such as the KEYNOTE-012 Phase I-b trial of pembrolizumab and CheckMate-141 of nivolumab, have shown that these drugs have similar efficacy and adverse events, most frequently hypothyroidism (J Clin Oncol. 2016;34:3838–3845; Oral Oncol. 2018;81:45–51). Both are both superior second-line agents compared to the standard of care approach in these patients, he said.
Patients in KEYNOTE-012 had an overall response rate of 18%, with 3% achieving a complete response, 15% achieving a partial response, and 20% achieving stable disease. There was also a correlation between PD-1 expression in tumor cells and improved survival. A subsequent Phase III trial of pembrolizumab, KEYNOTE-040, did not meet its primary endpoint of a 20% decrease in death compared to patients receiving chemotherapy, but median survival for the pembrolizumab patients was 8.4 months, compared to 7.1 months for those receiving chemotherapy, a significant response nonetheless, said Dr. Kim. In 2018, an updated presentation on KEYNOTE-040 showed that the drug did meet its overall survival goal.
In a 2017 Phase III trial of nivolumab, CheckMate-141, the immunotherapy agent had a better survival rate than the investigators’ chemotherapy of choice: methotrexate, docetaxel, or cetuximab. The study and a later follow-up showed that patients on nivolumab had a 30% decrease in risk of death, and patients with a higher expression of PD-L1 had a better response. Also, patients with P16-positive disease had a much better response to nivolumab than those with P16-negative disease. One reason may be that “because P16 tumors are induced by HPV, a foreign virus, the expression of the viral particles on the surface of the tumor cells may make them more antigenic, allowing the nivolumab to be more effective,” said Dr. Kim.
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