REMORA Trial of Lenvatinib in Thymic Carcinoma Confirms Efficacy

In the prospective phase 2 trial of lenvatinib (Lenvima) in patients with previously treated advanced or metastatic thymic carcinoma, the investigators led by Jun Sato, MD confirmed the antitumor activity and safety results for this regimen, showing it could become a standard treatment option for these patients.

For the 42 evaluable patients in this 1-arm study, the objective response rate (ORR) was 38% (90% CI, 25,6%-52.0%; P <.0001), which met the primary end point of ORR by independent central review. There were 16 (38%) patients with partial response and 24 (57%) with stable disease. The disease control rate was 95% (95% CI, 83.8%-99.4%). Between all of the patients who responded, the median time to first response was 2 months (IQR, 1.1-3.9); the median duration of response was 11.6 months (95% CI, 5.8-18.0).

The patients in the REMORA trial had pathologically confirmed unresectable advanced stage or metastatic disease. They received 24 mg of lenvatinib daily by mouth in 4-week cycles until their disease progressed or they had unacceptable adverse events (AEs). Patients received a median number of cycles with lenvatinib of 9.5 (range, 2-24) and the median duration of treatment was 8.8 months (IQR, 5.6-15.6). The median follow-up was 15.5 months (IQR, 13.1-17.5). Fourteen (33%) patients were still receiving therapy by cutoff date of February 22, 2019.

ORR by local investigator assessment was seen in 16 (38%) of the 42 patients (95% CI, 23.6%-54.4%). The median progression-free survival for patients on lenvatinib was 9.3 months (95% CI, 7.7-13.9); the median overall survival was not reached (95% CI,16.1 months-not reached). There was a probability of 41% for a 12-month progression-free survival and 83% for a 12-month overall survival.

In a subgroup analysis of these patients, 4 of 11 patients who were 65 years or older achieved an objective response, as well as 12 of 31 patients younger than 65. For the 14 patients with a bodyweight less than 58 kg, 5 had an objective response; 28 patients weighed 58 kg or more, of which 11 had objective response.

By the cutoff date, 28 (67%) patients had disease progression. Of those, 20 (48%) discontinued treatment due to disease progression. Fifteen (36%) patients had died¾13 (87%) from progressive disease and 2 from unknown causes; the local investigators decided there was no causal relationship between these deaths and the drug being studied. There were no patient deaths due to treatment-related AEs (TRAEs).

The most common TRAEs were hypertension in 88% of patients, palmar-plantar erythrodysaesthesia syndrome in 69%, decreased platelet count kin 52%, and diarrhea in 50%. For grade 3 events, the most common were hypertension and palmar-plantar erythrodysaesthesia syndrome at 64% and 7%, respectively. There was 1 patient with drug-induced grade 3 pneumonitis and their condition improved when given steroids.

AEs which caused 7 (17%) patients to discontinue lenvatinib included intestine perforation, ventricular dysfunction, pneumonitis, arthralgia, and pneumothorax. Serious AEs developed in 8 (19%) patients: large intestine perforation, left ventricular dysfunction, pneumonitis, abdominal pain, electrocardiogram T wave abnormal, pneumonia, decreased appetite, and upper abdominal pain.

Every patient in the trial received at least 1-step dose reduction of lenvatinib of 4 mg due to AEs. The main AEs to cause a need for dose reduction were proteinuria, hypertension, and palmar-plantar erythrodysaesthesia syndrome.

Baseline characteristics for these patients included a history of treatment at least 1 platinum-based chemotherapy in all patients and 25 (60%) patients with at least 2 prior lines of platinum therapy. There were 3 (7%) patients who had previously received immune checkpoint inhibitors. One patient had rheumatoid arthritis, although it was not exacerbated on this study, and one patient had asymptomatic brain metastasis but did not develop neurological symptoms during the trial.

“This multicenter, phase 2 trial confirmed the durable response of lenvatinib in advanced, previously treated thymic carcinoma,” the investigators concluded in their discussion. “We believe that lenvatinib could be a standard second-line treatment option for patients with thymic carcinoma.”

_Reference:

_{Sato J, Satouchi M, Itoh S, et al. Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial. Lancet Oncol. 2020;21(6):843–850. doi:10.1016/s1470-2045(20)30162-5}