The combination of Lenvima (lenvatinib), an oral kinase inhibitor, and the immunotherapy Keytruda (pembrolizumab), a PD-1 inhibitor, showed promising benefits for the treatment of patients with liver cancer (or hepatocellular carcinoma) that cannot be removed by surgery (unresectable). This drug combination was also shown to be safe, according to the results of a clinical trial presented at the 2020 ASCO annual meeting by Andrew X. Zhu, MD, PhD, Director, Liver Cancer Research, Massachusetts General Hospital, Boston.
“Multi-kinase inhibition with lenvatinib plus PD-1 inhibition with pembrolizumab results in promising anti-tumor activity, as evidenced by a high objective response rate and disease control rate,” Dr. Zhu reported.
Lenvatinib is a targeted therapy that is currently approved by the FDA for the treatment of liver cancer that cannot be removed by surgery in patients who have not received any previous therapy. Pembrolizumab is an immunotherapy that is approved by the FDA for the treatment of liver cancer in patients who have already received treatment with Nexavar (sorafenib), a standard treatment for liver cancer.
In this new study, Dr. Zhu and colleagues evaluated the efficacy and safety of the combination of lenvatinib and pembrolizumab in 100 patients with unresectable liver cancer.
According to Dr. Zhu, by the time of data collection at end of October 2019, 37 of the 100 patients in the study were still receiving treatment, including 34 patients who were receiving the 2 drugs and 3 patients who were receiving lenvatinib alone.
Almost 40% of patients were able to continue treatment with the combination of lenvatinib and pembrolizumab, which suggests that the drugs are safe and tolerable.
“Overall, there were no new or unexpected toxicities resulting from lenvatinib plus pembrolizumab combination therapy,” said Dr. Zhu.
According to the investigators, imaging tests showed that in the majority (more than 80%) of patients the tumor was shrinking, and these reductions continued for many months, between 9 months and 13 months.
In addition, treatment with this combination resulted in about 9 months of no disease progression for these patients. The percentage of patients whose tumors responded to therapy was between 36% and 46%, depending on the method used to measure a response. The disease was controlled, meaning the tumor was reduced or remained stable, in almost 90% of the patients.
After receiving treatment for about 8 months, almost all (95%) of the patients had at least 1 treatment-related side effect. A total of 67% of the patients had a serious (grade 3 or worse) side effect, including 63% with grade 3, 1% with grade 4 side effect, and 3 patients died. The 3 deaths were, 1 each, related to respiratory failure, abnormal liver function, and intestinal perforation (tear in the intestine).
“The most common treatment-related adverse events included hypertension, diarrhea, fatigue, decreased appetite, and hypothyroidism,” Dr. Zhu reported.
“However, most of these were grade 1 or grade 2,” he noted. Grade 1 and 2 side effects are mild and moderate and typically resolve on their own or with minimal management.
A much larger phase 3 clinical trial is currently evaluating the combination of lenvatinib plus pembrolizumab versus lenvatinib alone in patients with unresectable liver cancer. The results of this trial will provide further data on the safety and efficacy of treatment with lenvatinib plus pembrolizumab in this patient population.
- Treatment with lenvatinib plus pembrolizumab is safe and effective for patients with unresectable liver cancer
- More than 80% of patients with liver cancer had tumor shrinkage, which lasted 9 to 13 months
- Between 36% and 46% of patients’ tumors responded to the combination treatment
- In nearly 90% of the patients, the tumor was reduced or remained stable for the length of the study period