Improved Overall Survival and Reduced Disease Progression in Patients Failing Tagrisso Treatment
The combination therapy of 슬롯사이트 볼트 (amivantamab) and chemotherapy as a second-line treatment for EGFR-mutated, locally advanced, or metastatic non-small cell lung cancer (NSCLC) has demonstrated sustained improvement in overall survival (OS) compared to chemotherapy alone.
On September 14th, the ESMO Annual Meeting featured results from the secondary analysis of the MARIPOSA-2 study, which compared 슬롯사이트 볼트 and chemotherapy to chemotherapy alone for patients who had progressed after Tagrisso (osimertinib) treatment. The analysis, conducted after a median follow-up of 18.1 months, builds upon last year’s interim results presented at ESMO, which were based on 8.7 months of follow-up.
This year’s data focused solely on the 슬롯사이트 볼트 and chemotherapy combination group. Data on the cohort with Leclaza (lazertinib) were not disclosed.
At 18.1 months, the OS for the 슬롯사이트 볼트 combination group was 17.7 months, compared to 15.3 months in the chemotherapy group. The survival rate for both groups was 50%.
Dr. Sanjay Popat from the Royal Marsden Hospital and Institute of Cancer Research in the UK, who presented the findings, commented, “The 슬롯사이트 볼트 combination group showed a numerical improvement in OS compared to chemotherapy. While the data are clinically meaningful, they did not reach the pre-specified threshold for statistical significance. Further follow-up is required."
The 슬롯사이트 볼트 combination also improved PFS2 (progression-free survival from first-line treatment to disease progression or death during or after second-line treatment), aligning with the OS results. The median PFS2 was 16 months for the 슬롯사이트 볼트 group, versus 11.6 months for chemotherapy, marking a 36% reduction in the risk of disease progression or death during second-line treatment (HR=0.64, 95% CI: 0.48-0.85, p=0.002).
Additionally, time to symptomatic progression, an important secondary efficacy endpoint, was 16 months in the 슬롯사이트 볼트 group compared to 11.8 months in the chemotherapy group (HR=0.73, 95% CI: 0.55-0.96, p=0.026). This endpoint is crucial for assessing patients' quality of life during treatment.
The time to treatment discontinuation was 10.4 months for the 슬롯사이트 볼트 group versus 4.5 months for chemotherapy (HR=0.42, 95% CI: 0.33-0.53, p<0.0001). Time to subsequent therapy, or the time between second- and third-line treatments, was also prolonged, at 12.2 months for the 슬롯사이트 볼트 group compared to 6.6 months for chemotherapy (HR=0.51, 95% CI: 0.39-0.65, p<0.0001).
Dr. Popat added, "With the extended follow-up period of the MARIPOSA-2 study, we confirmed that the 슬롯사이트 볼트 and chemotherapy combination is more effective than chemotherapy alone in second-line treatment for EGFR-mutated advanced NSCLC. The post-progression endpoints also showed continued improvement, and the final OS analysis is ongoing."
In addition to the MARIPOSA-2 findings, the MARIPOSA study, which compares the combination of 슬롯사이트 볼트 and Leclaza with Tagrisso monotherapy in first-line NSCLC treatment, was also highlighted. The study focuses on whether the 슬롯사이트 볼트-Leclaza combination can better prevent resistance mutations compared to Tagrisso.
Dr. Benjamin Besse from the Gustave Roussy Institute in France discussed the MARIPOSA study’s sub-analysis. "In the Tagrisso group, 13.6% of patients had MET amplification mutations, while only 4.4% of those in the 슬롯사이트 볼트-Leclaza group showed similar mutations. Secondary EGFR resistance mutations were observed in 7.9% of the Tagrisso group but just 0.9% in the 슬롯사이트 볼트 combination group, a significant reduction."
The study also showed benefits in resistance mechanisms independent of MET and EGFR, such as HER2 amplification, RAS/RAF mutations, PI3K mutations, cell cycle alterations, and TP53/RB1 deficiencies.
Dr. Besse emphasized, "TP53/RB1 loss, a known biomarker for the transformation of NSCLC into small cell lung cancer (SCLC), occurred in 2.9% of patients treated with Tagrisso, compared to just 0.9% in the 슬롯사이트 볼트 combination group."
He concluded, "The 슬롯사이트 볼트-Leclaza combination therapy offers a potential option to reduce the scope and complexity of resistance mechanisms compared to Tagrisso monotherapy."
In a discussion session, Professor Jurgen Wolf from the University of Cologne, Germany, highlighted the limitations of the study.
"While the MARIPOSA-2 study continues to show benefits with the 슬롯사이트 볼트 and chemotherapy combination, the targeted therapy of 슬롯사이트 볼트 and Leclaza is akin to firing an expensive and toxic arrow. The challenge is how to strategically develop these treatments for maximum effectiveness," Wolf explained.
He added, "As seen in the MARIPOSA sub-analysis, while 슬롯사이트 볼트 and Leclaza target MET and EGFR mutations effectively, overcoming immune evasion, treating all mutations in NSCLC remains a challenge, akin to cauterizing each head of the Hydra."