FDA Approves Genentech's Tecentriq Plus Lurbinectedin as First-Line Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer
核心洞察
The FDA has approved Genentech's Tecentriq in combination with lurbinectedin as the first and only combination therapy for first-line maintenance treatment of extensive-stage small cell lung cancer (搜索).
The Phase III IMforte study demonstrated that the combination reduced the risk of disease progression or death by 46% and the risk of death by 27% compared to Tecentriq alone.
The approval addresses a critical unmet need in ES-SCLC (搜索), a highly aggressive disease with limited treatment options and high relapse rates.
The U.S. Food and Drug Administration has approved Genentech's Tecentriq (atezolizumab) and Tecentriq Hybreza (atezolizumab and hyaluronidase-tqjs) in combination with lurbinectedin (Zepzelca) for the maintenance treatment of adult patients with extensive-stage small cell lung cancer (搜索) (ES-SCLC (搜索)). This landmark approval represents the first and only combination therapy for first-line maintenance treatment of ES-SCLC, addressing a critical gap in managing this highly aggressive disease.
The approval applies to patients whose disease has not progressed after first-line induction therapy with Tecentriq or Tecentriq Hybreza, carboplatin and etoposide. The U.S. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology have been updated to include the regimen as a category 2A and preferred option for maintenance treatment of people with ES-SCLC (搜索) following induction therapy with Tecentriq and chemotherapy.
Clinical Trial Results Drive Approval
The FDA approval is based on results from the Phase III IMforte study, which demonstrated significant clinical benefits for the combination therapy. The study showed that Tecentriq plus lurbinectedin reduced the risk of disease progression or death by 46% and the risk of death by 27% compared to Tecentriq maintenance therapy alone.
Following 3.2 months of induction therapy, the median overall survival for the Tecentriq plus lurbinectedin regimen was 13.2 months versus 10.6 months for Tecentriq alone (stratified hazard ratio [HR]=0.73; 95% CI: 0.57–0.95; p=0.0174). Median progression-free survival by independent assessment was 5.4 months versus 2.1 months, respectively (stratified HR=0.54; 95% CI: 0.43–0.67; p<0.0001).
Study Design and Patient Population
IMforte [NCT05091567] is a Phase III, open-label, randomized trial evaluating the efficacy and safety of Tecentriq plus lurbinectedin versus Tecentriq alone as first-line maintenance therapy for adults (≥18 years) with extensive-stage small-cell lung cancer. The study enrolled 660 patients in the induction phase and randomized 483 patients in the maintenance phase.
Patients first received induction therapy with Tecentriq, carboplatin and etoposide for four 21-day cycles. Those without disease progression were then randomized 1:1 to receive maintenance therapy with either Tecentriq plus lurbinectedin or Tecentriq alone until disease progression or unacceptable toxicity. The study's primary endpoints were independent review facility-assessed progression-free survival and overall survival from randomization into the maintenance phase.
Clinical Significance for ES-SCLC Management
"For people with extensive-stage small cell lung cancer (搜索) and their families, the period after induction therapy is often filled with uncertainty, given the high risk of relapse," said Roy Herbst, M.D., Ph.D., deputy director and chief of medical oncology and hematology at Yale Cancer Center and Smilow Cancer Hospital. "The Tecentriq and Zepzelca combination provides a new option and a proactive approach in this setting shown to improve progression-free and overall survival in patients who haven't progressed after standard induction treatment with Tecentriq and chemotherapy."
Herbst noted that "the approval may lead to a meaningful shift in how we manage this challenging disease and gives us a new tool to help to delay disease progression and extend survival."
Safety Profile and Tolerability
Safety was generally consistent with the known safety profiles of Tecentriq and lurbinectedin. The trial is sponsored by Genentech and co-funded by Jazz Pharmaceuticals.
Building on Established ES-SCLC Treatment
Today's approval builds on Tecentriq's established role in ES-SCLC (搜索). In 2019, the FDA approved Tecentriq in combination with chemotherapy for the first-line treatment of adults with ES-SCLC, based on the IMpower133 study, which at the time was the first new treatment option in two decades for this patient population.
"The Tecentriq and lurbinectedin combination reduced the risk of disease progression or death by nearly half," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development at Genentech. "We are proud to deliver this advancement for the small cell lung cancer (搜索) community in partnership with Jazz Pharmaceuticals, as it reflects our abiding commitment to improving outcomes in the hardest-to-treat cancers."