Lurbinectedin Plus Atezolizumab Approved for Maintenance Treatment in ES-SCLC After Induction Therapy
Expert Perspectives · Lyn Brook · 2025-10-06
The FDA has approved lurbinectedin (Zepzelca™, Jazz Pharmaceuticals, Inc.) plus atezolizumab (Tecentriq®, Genentech Inc.) or atezolizumab and hyaluronidase‑tqjs (Tecentriq Hybreza®, Genentech Inc.) for the maintenance treatment of adults with extensive‑stage small–cell lung cancer (ES‑SCLC) whose disease has not progressed following first‑line induction with atezolizumab or atezolizumab and hyaluronidase‑tqjs, carboplatin, and etoposide.
Why This Approval Matters
This approval adds the first lurbinectedin‑based maintenance regimen to consolidate benefit after chemoimmunotherapy induction in ES‑SCLC, demonstrating clinically meaningful improvements in overall survival (OS) and progression‑free survival (PFS) versus atezolizumab maintenance alone. The availability of both intravenous (IV) atezolizumab and the subcutaneous (SC) atezolizumab/hyaluronidase formulation provides flexibility in delivery during the maintenance phase.
Breaking Down the IMforte Trial
Efficacy was evaluated in IMforte (NCT05091567), a randomized, multicenter, open‑label trial in patients with ES‑SCLC receiving first‑line therapy. After completing four cycles of induction with atezolizumab, carboplatin, and etoposide, 483 patients without disease progression were randomized 1:1 to receive either:
- Lurbinectedin plus atezolizumab IV
- Atezolizumab IV alone
Major efficacy end points were OS and PFS by an independent review facility (IRF) using RECIST v1.1, measured at the point of randomization post‑induction. Results favored the combination:
- OS: 13.2 months with lurbinectedin plus atezolizumab versus 10.6 months with atezolizumab alone
- PFS: 5.4 months with lurbinectedin plus atezolizumab versus 2.1 months with atezolizumab alone
Managing Adverse Events
Lurbinectedin prescribing information includes warnings and precautions for myelosuppression, hepatotoxicity, extravasation leading to tissue necrosis, rhabdomyolysis, and embryo‑fetal toxicity. Atezolizumab and atezolizumab/hyaluronidase‑tqjs labeling carry warnings for severe and fatal immune‑mediated adverse reactions, infusion‑related reactions, complications of allogeneic HSCT, and embryo‑fetal toxicity. Clinicians should monitor counts, hepatic function, and immune‑related toxicities, and manage per established guidelines.
Dosing and Administration
- Lurbinectedin: 3.2 mg/m² IV infusion every 21 days, until disease progression or unacceptable toxicity
- Atezolizumab (IV): 840 mg every two weeks, 1,200 mg every three weeks, or 1,680 mg every four weeks, until progression or unacceptable toxicity
- Atezolizumab and hyaluronidase‑tqjs (SC): 1,875 mg atezolizumab plus 30,000 units hyaluronidase every three weeks, until progression or unacceptable toxicity