The US Food and Drug Administration (FDA) has approved a lurbinectedin (Zepzelca, Jazz Pharmaceuticals, Inc.)-based combination therapy for the maintenance treatment of certain adults with extensive-stage small cell lung cancer (ES-SCLC).

Specifically, lurbinectedin is now approved in combination with atezolizumab (Tecentriq, Genentech Inc.) or atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza, Genentech Inc.) for patients whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab plus hyaluronidase-tqjs, carboplatin, and etoposide, according to the FDA approval notice.

Lurbinectedin was initially approved in June 2020 for the treatment of adults with metastatic SCLC who progressed on or after platinum-based chemotherapy. 

“The [new] approval marks the first combination therapy for first-line maintenance treatment of ES-SCLC, a fast-growing and aggressive cancer with limited treatment options,” Jazz Pharmaceuticals said in a press release.

Approval was based on significant improvements in overall survival (OS) and progression-free survival (PFS) as demonstrated in the randomized, open-label, phase 3 IMforte trial of 483 patients with ES-SCLC whose disease had not progressed after completion of four cycles of atezolizumab, carboplatin, and etoposide for induction therapy. Patients were randomly assigned 1:1 to receive either intravenous lurbinectedin plus atezolizumab or intravenous atezolizumab alone until disease progression or unacceptable toxicity. 

Median OS was 13.2 vs 10.6 months in the treatment arms, respectively, and median PFS was 5.4 vs 2.1 months, respectively. Adverse reactions occurring in at least 30% of patients in the combination therapy arm were decreased lymphocytes, decreased platelets, decreased hemoglobin, decreased leukocytes, decreased neutrophils, nausea, and fatigue/asthenia.

The findings were reported at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The Lancet. 

The National Comprehensive Cancer Network subsequently updated its Clinical Practice Guidelines in Oncology for SCLC to include the lurbinectedin and atezolizumab combination therapy as the preferred maintenance regimen for patients whose disease has not progressed following four cycles of platinum-based chemotherapy and atezolizumab induction, Jazz Pharmaceuticals noted in the press release.

"For people with extensive-stage small cell lung cancer and their families, the period after induction therapy is often filled with uncertainty, given the high risk of relapse," stated Roy Herbst, MD, PhD, deputy director and chief of medical oncology and hematology at Yale Cancer Center and Smilow Cancer Hospital. "[This] combination provides a new option and a proactive approach in this setting … [and] 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." 

Prescribing information for lurbinectedin includes warning and precautions for myelosuppression, hepatotoxicity, extravasation resulting in tissue necrosis, rhabdomyolysis, and embryo-fetal toxicity. Prescribing information for atezolizumab and for atezolizumab and hyaluronidase-tqjs — a subcutaneously administered atezolizumab option — includes warnings and precautions for severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

The recommended treatment dose for lurbinectedin is 3.2 mg/m² intravenously every 21 days until disease progression or unacceptable toxicity. The recommended dose for atezolizumab is 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks; and the recommended dose for atezolizumab and hyaluronidase-tqjs is 1875 mg and 30,000 units, respectively, given subcutaneously every 3 weeks until disease progression or unacceptable toxicity.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter