Weigh Benefit Against Burden: Defining Lurbinectedin’s Role in a Shifting Small Cell Lung Cancer Landscape

Welcome to OncLive On Air®! I’m your host today, Caroline Seymour.

OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, we spoke with Triparna Sen, PhD, and Jacob Sands, MD. Dr Sen is a professor of internal medicine and the director of the Lung Cancer Preclinical Therapeutics Platform at the Ohio State University Comprehensive Cancer Center—James in Columbus. Dr Sands is associate chief of the Lowe Center for Thoracic Oncology and the oncology medical director of the International Patient Center at Dana-Farber Cancer Institute, as well as an assistant professor at Harvard Medical School in Boston, Massachusetts.

In our exclusive interview, Drs Sen and Sands discussed findings from the phase 3 IMforte trial (NCT05091567), which showed that adding lurbinectedin (Zepzelca) to atezolizumab (Tecentriq) maintenance following carboplatin, etoposide, and atezolizumab induction improved outcomes in patients with extensive-stage small cell lung cancer (SCLC). Dr Sen noted that although the regimen’s safety profile was manageable, the combination does increase rate of hematologic toxicities, including anemia, neutropenia, and thrombocytopenia, so the key question is whether the added treatment burden is justified by longer disease control and survival. Dr Sands added that the neutropenia rates in IMforte were lower than in the earlier second-line lurbinectedin experience, likely because primary prophylaxis, such as granulocyte colony-stimulating factor, was permitted.

The experts also weighed in on a trial in progress presented at the 2026 World Conference on Lung Cancer evaluating lurbinectedin plus durvalumab (Imfinzi) as maintenance therapy. Dr Sen explained that a positive result could show that the strategy is reproducible with a different PD-L1 inhibitor and induction regimen but cautioned against assuming a class-wide effect or treating the 2 regimens as interchangeable. Dr Sands said he would not expect durvalumab to perform differently from atezolizumab in this context, and that the more pressing question is whether lurbinectedin belongs in maintenance at all, particularly as the IMforte curves have converged with longer follow-up. Both experts pointed to the phase 3 DeLLphi-305 trial (NCT06211036) of tarlatamab (Imdelltra) plus durvalumab vs durvalumab alone as first-line maintenance, which has reported positive OS and PFS results via press release, as the most significant development to watch in this space.

Turning to the relapsed setting, Drs Sen and Sands discussed the negative phase 3 LAGOON trial (NCT05153239), in which neither lurbinectedin monotherapy nor lurbinectedin plus irinotecan improved OS vs investigator’s choice of topotecan (Hycamtin) or irinotecan, leading to the withdrawal of lurbinectedin’s second-line indication. Dr Sands highlighted that the control arm median OS was unexpected given the median OS data that supported the original accelerated approval of the agent. Both experts emphasized that the LAGOON results should not be conflated with the maintenance data, and Dr Sands expressed hope that lurbinectedin remains a guideline-listed option in later lines, citing its convenient every-3-week dosing.

Finally, the experts looked ahead to emerging therapies. Dr Sands discussed B7-H3–directed antibody-drug conjugates (ADCs), including YL201 and ifinatamab deruxtecan. He also outlined practical toxicity management for ADCs, including cytopenias, nausea, fatigue, alopecia counseling, and the challenge of distinguishing drug-related interstitial lung disease from waxing and waning inflammatory findings common in SCLC. Dr Sen highlighted anticipated data at the 2026 ESMO Congress and stressed that treatment selection in SCLC maintenance will depend on magnitude of benefit, patient selection, toxicity, and center capabilities rather than a one-size-fits-all approach.

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