‘I’ll recommend Lumakras for KRAS G12C-mutant lung cancer patients without hesitation’

"The therapeutic benefit of sotorasib for patients with KRAS G12C genetic variant NSCLC has been clinically proven. If a patient can afford it after first-line standard therapy, I recommend sotorasib without hesitation."

Professor Lee Se-hoon of the Department of Hematology-Oncology at Samsung Medical Center said so at the 22nd Spring Symposium of the Korean Society of Medical Oncology (KSMO), held at Lotte Hotel Seoul on May 17. He stressed that he is confident of the treatment efficacy of Amgen’s sotorasib-based drug, Lumakras.

In his presentation titled "The latest knowledge on sotorasib’s efficacy in patients with pretreated KRAS G12C NSCLC," Professor Lee introduced data from key clinical trials of Lumakras and shared his experience with the treatment.

Lumakras is a highly anticipated drug for its potential to treat KRAS-mutated NSCLC, a disease that has long remained difficult to treat. Based on the phase 2 clinical trial (CodeBreaK 100), the U.S. FDA accelerated its approval.

"When the CodeBreaK 100 clinical data came out, it received a lot of applause in the clinical field," Professor Lee said. “It showed a response rate of about 37 percent in patients with KRAS G12C gene-mutated NSCLC who had received chemotherapy, with some patients showing significant Depth of Tumor response."

"The duration of response (DoR) for sotorasib was about 11 months, which is good. When considering response rates, we believe that DoR data is a more meaningful metric than PFS data of 6.8 months because, at response rates in the 30-40 percent range, there is a complete split between those who responded and those who did not respond.

Professor Lee explained the significance of the phase 3 (CodeBreaK 200) study, "As a clinician, the question was 'Should I use sotorasib or docetaxel after first-line standard therapy?' CodeBreaK 100 has been proven effective, but it is very expensive, so we were worried about the cost-effectiveness ratio, and CodeBreaK 200 compared this point.”

"With CodeBreaK 200, the PFS at one year was about 24.8 percent, which is quite significant," Lee said, referring to a patient who participated in the clinical trial. "The hazard ratio (HR) was also 0.66, which is a meaningful result, and clinicians felt the benefit. We could feel that the drug show efficacy right away."

Lee explained that another notable data point was the time to response (TTR), which was faster in sotorasib (1.4 months) than in docetaxel (2.8 months). In clinical experience, TTR correlates with the depth of tumor response. He added that faster TTR can be interpreted as a faster onset of effect and a deeper tumor response.

"In terms of adverse events, we are also quite encouraged. Although some grade 3 responses are observed, diarrhea and elevated liver levels are manageable," Professor Lee said. "One patient in the CodeBreaK 200 trial has been on sotorasib for two years and four months. However, the prerequisite is that the CNS metastases are managed consistently. This is very important."

Lee shared an experience with another patient.

"The emergence of KRAS G12C mutation treatment agents, along with the popularization of NGS, has interested us in patients with multiple gene mutations," he said. "A patient with KRAS G12C mutation and STK11 mutation participated in the sotorasib trial because he had problems using immuno-oncology drugs, and he had a near complete response (CR) and has been using it well for one year and six months."

Furthermore, Professor Lee shared a case of a patient who used Lumakras as a second-line treatment after immuno-oncology but discontinued the treatment due to liver toxicity, including elevated liver function tests (LFTs), and the patient requested to use Lumakras again.

"When I was thinking about re-prescribing sotorasib, I reviewed the results of previous studies and found that the average time between using sotorasib after using immuno-oncology drugs was 39 days for the group with liver toxicity and 131 days for the group without liver toxicity, which was a statistically significant difference," Lee said. "It can be seen that liver toxicity is different after 90 days or more after using immuno-oncology drugs."