High response rates in gastric cancer treatment with immunotherapy plus a targeted drug – pembrolizumab and lenvatinib

The Lancet Oncology reported a single-center Japanese phase II clinical trial in which Kawazoe and colleagues investigated first- or second-line treatment with lenvatinib and pembrolizumab in patients with advanced gastric cancer and found a high objective response rate.

Summary of the results

• An objective response was observed in 69% of patients, while the remaining patients had stable disease.
• PD-L1 CPS value was associated with response rates of 84% in patients with CPS ≥1 and 40% in those with CPS <1.

Details of the study

Between October 2018 and March 2019, the study enrolled patients with metastatic (advanced) gastric or gastroesophageal junction adenocarcinoma, for a total of 29 patients. The patients received 20 mg of lenvatinib daily (a targeted drug) and 200 mg of pembrolizumab every 3 weeks (immunotherapy) until cancer progression or unacceptable adverse effects. The study's primary endpoint was the objective response rate.

Results

• The median follow-up was 12.6 months.
• An objective response was observed in 20 of the 29 patients (69%), with a complete response in 1 patient.
• An additional nine patients (31%) had stable disease.
• A response was observed in 10 of the 14 patients (71%) receiving this two-drug treatment as first-line therapy and in 10 of the 15 patients (67%) receiving it as second-line therapy.
• The median progression-free survival was 7.1 months.
• The median overall survival had not been reached.

In a further analysis, an objective response was observed in 16 of the 19 PD-L1-positive patients (84%) and in 4 of the 10 PD-L1-negative patients (40%). Among these patients, the median progression-free survival was 9.1 months and 5.9 months, respectively. Tumor mutational burden (TMB) data were available for 21 patients. A response was observed in 9 of the 11 patients with a high TMB score (82%) and in 6 of the 10 patients with a low TMB score (60%).

Adverse effects

Treatment-related grade 3 (serious) adverse effects occurred in 14 patients (48%). The most frequently reported were hypertension in 11 patients (38%), proteinuria in 5 patients (17%) and a decreased platelet count in 2 patients (7%). No treatment-related grade 4 adverse effects were observed.

Serious adverse effects were observed in four patients (14%), including grade 2 jaundice, grade 3 heart failure, grade 3 gastric bleeding and gastric perforation in one patient. None of the events was considered treatment-related. No treatment-related deaths were reported.

In conclusion lenvatinib plus pembrolizumab showed promising antitumor activity with an acceptable safety profile in patients with advanced gastric cancer. Based on these results, a confirmatory and more comprehensive phase-III clinical trial will be planned in the future.

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Lenvatinib (Lenvima), a targeted cancer drug taken orally as a pill, had previously received approvals for thyroid cancer in 2015, kidney cancer in combination with everolimus in 2016, liver cancer in 2018 and uterine cancer in combination with pembrolizumab in 2019 from the FDA. Lenvatinib works by preventing the function of a receptor called a tyrosine kinase receptor, which is located on the cell membrane. Tyrosine kinase receptors generally play a role in cancer cell growth, proliferation, new blood vessel formation and spread to distant tissues.

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