Tuesday, April 16, 2024

Breakthrough in Esophageal Cancer Treatment: FDA Greenlights Tevimbra as Second-Line Monotherapy

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The US Food and Drug Administration (FDA) has granted approval to tislelizumab-jsgr (marketed as Tevimbra by BeiGene, Ltd.) for use as second-line monotherapy in specific adult patients diagnosed with unresectable or metastatic esophageal cancer (ESCC). This approval pertains to individuals who have previously undergone systemic chemotherapy that did not involve a programmed death–ligand 1 (PD-L1) inhibitor.

The recent approval of tislelizumab-jsgr (Tevimbra, BeiGene, Ltd.) by the US Food and Drug Administration (FDA) marks a significant milestone in the treatment landscape for patients grappling with unresectable or metastatic esophageal cancer as a second-line monotherapy. This novel checkpoint inhibitor, now greenlit for clinical use, represents a beacon of hope for individuals who have experienced disease progression following prior systemic chemotherapy devoid of a programmed death–ligand 1 (PD-L1) inhibitor.

The pivotal decision by the FDA to approve tislelizumab-jsgr was informed by robust clinical evidence gleaned from the phase 3 RATIONALE 302 trial. This open-label study enrolled a diverse cohort of 512 adult participants drawn from 123 research sites dispersed across 11 countries spanning Europe, Asia, and North America. Within this multinational trial, patients were randomized to receive either intravenous tislelizumab or standard chemotherapy options such as paclitaxel, docetaxel, or irinotecan. The treatment was administered until the occurrence of disease progression, unacceptable toxicity, or the voluntary withdrawal of participation from the study.

Tislelizumab Outperforms Standard Chemotherapy in Esophageal Cancer Trial, Offering New Hope for Advanced Cases

Throughout the RATIONALE 302 trial, tislelizumab-jsgr showcased its potential as a game-changing therapeutic option for patients grappling with advanced esophageal cancer. Notably, the trial’s primary endpoint, overall survival, demonstrated a statistically significant and clinically meaningful improvement with tislelizumab compared to conventional chemotherapy regimens. In the intention-to-treat population, the median overall survival clocked in at 8.6 months with tislelizumab, significantly outpacing the 6.3 months observed in the chemotherapy arms. Importantly, this survival advantage was observed across various predefined subgroups, including baseline PD-L1 status and geographic region.

Moreover, the clinical benefits of tislelizumab-jsgr extended beyond mere survival outcomes. The novel checkpoint inhibitor was associated with an enhanced overall response rate compared to standard chemotherapy (20.4% vs. 9.8%) and a significantly prolonged duration of response (median of 7.1 vs. 4.0 months). These findings underscore the therapeutic promise of tislelizumab in achieving durable and clinically meaningful responses among patients grappling with advanced ESCC.

However, as with any therapeutic intervention, the use of tislelizumab-jsgr may be accompanied by certain adverse reactions. The most commonly reported adverse events included alterations in glucose levels, hemoglobin levels, lymphocyte counts, sodium levels, and albumin levels, as well as fluctuations in alkaline phosphatase, anemia, fatigue, aspartate aminotransferase levels, musculoskeletal pain, weight loss, alanine aminotransferase levels, and cough.

Esophageal Cancer

FDA-Approved Tislelizumab Sets New Standard for Esophageal Cancer Treatment

In terms of safety, the incidence of grade 3 or greater treatment-emergent adverse events was lower among patients receiving tislelizumab compared to those on standard chemotherapy (46% vs. 68%). Moreover, fewer patients discontinued tislelizumab treatment due to adverse events compared to those receiving chemotherapy (7% vs. 14%). These findings underscore the favorable safety profile of tislelizumab-jsgr and its potential to be well-tolerated among patients with advanced esophageal cancer.

The approval of tislelizumab-jsgr by the FDA heralds a new era in the management of advanced esophageal cancer and underscores the critical importance of precision medicine in oncology. With its proven efficacy, favorable safety profile, and potential to revolutionize treatment paradigms, tislelizumab-jsgr represents a beacon of hope for patients grappling with this devastating disease. As this novel checkpoint inhibitor becomes available for clinical use in the United States, it holds the promise of improving outcomes and enhancing the quality of life for individuals battling advanced esophageal cancer.

Results from the RATIONALE 302 trial demonstrated a statistically significant and clinically meaningful improvement in overall survival among patients treated with tislelizumab compared to those receiving chemotherapy alone. Median overall survival in the intention-to-treat population, the primary study endpoint, was 8.6 months with tislelizumab versus 6.3 months with chemotherapy. This survival benefit was consistent across various subgroups, including baseline PD-L1 status and geographical region. Moreover, tislelizumab exhibited enhanced overall response rates and longer-lasting responses compared to chemotherapy.

Promising Esophageal Cancer Therapy with a Favorable Safety Profile and Potential New Indications

Common adverse reactions associated with tislelizumab treatment included alterations in glucose levels, hemoglobin levels, lymphocytes, sodium levels, and albumin levels, as well as increased alkaline phosphatase, anemia, fatigue, aspartate aminotransferase levels, musculoskeletal pain, weight loss, alanine aminotransferase levels, and cough. Notably, fewer patients experienced grade 3 or greater treatment-related adverse events with tislelizumab compared to chemotherapy, and fewer discontinued treatment due to adverse events.

Dr. Syma Iqbal from the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, emphasized the significance of tislelizumab as a treatment option for patients with advanced or metastatic ESCC. The approval, which had been postponed in 2022 due to COVID-19-related limitations, marks the first for the agent in the United States. It is anticipated that tislelizumab will be accessible in the US market during the second half of 2024, as announced by BeiGene.

Furthermore, BeiGene has disclosed that the FDA is currently reviewing a Biologics License Application for tislelizumab as a first-line treatment option for patients with unresectable, locally advanced, or metastatic ESCC, as well as for individuals with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

 

Resource: Med Scape, March 14, 2024

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