TCE TALK | Tarlatamab in Difficult-to-Treat SCLC and the Chinese DLL3-TCE Consensus

Small cell lung cancer (SCLC) is highly aggressive, proliferates rapidly, and metastasizes early. Although chemotherapy combined with immunotherapy is the first-line standard for extensive-stage SCLC (ES-SCLC), most patients still progress within a year, and treatment options after relapse are limited with poor prognosis. Tarlatamab, a DLL3-targeted bispecific T-cell engager (TCE), bridges T cells and tumor cells through a directed-immunity mechanism to mediate precise killing. It has brought a breakthrough for relapsed SCLC and is driving treatment earlier in the course of disease.

TCE TALK is a series of academic programs focused on innovative SCLC treatment that brings together leading experts in lung cancer to advance care through frontier dialogue and shared experience. This installment, held under the theme "To Conquer Expectations — from DeLLphi to the clinic, where TCE clinical performance exceeds expectations," continues the discussion with Prof. Qin Lili and Prof. Qin Haifeng of Beijing GOBROAD Hospital and Prof. Liu Xiaoqing of the Fifth Medical Center of the Chinese PLA General Hospital, focusing on the management of difficult-to-treat patients and the practical implementation of the Chinese expert consensus, to provide clinical guidance for the standardized and safe use of tarlatamab.

Difficult-to-Treat Patients: Hold the Safety Line, Still Fight for the Chance

Randomized controlled trials set strict limits on performance status and organ function, and a large number of patients with relapsed disease in the real world cannot meet them. A multicenter retrospective analysis showed that nearly 60% of real-world patients would not have met trial eligibility criteria, and this population had higher rates of disease progression, shorter treatment duration, and more ICANS. The prognostic differences in these out-of-window patients stem mainly from baseline characteristics rather than from the drug itself, suggesting that, provided the safety line is strictly held, treatment can be extended cautiously and in an orderly way to more complex populations — but with reasonable expectations and without indiscriminate expansion.

Prof. Qin Haifeng notes that patients with ECOG performance status of 2 or higher, the very elderly, and those with concurrent respiratory failure are precisely the group with the most urgent treatment need, yet they are the ones excluded from trials. Encouragingly, these patients can still achieve rapid and even better-than-expected tumor responses with tarlatamab, which strengthens clinicians' confidence in using the drug. He also emphasizes, however, that such patients often carry higher risks of CRS and ICANS, so fighting for the chance must be premised on holding the safety line, and indiscriminate use must be avoided. Prof. Liu Xiaoqing adds that when a new drug first reaches the market, patients should initially be selected and treated according to the registrational trial population, so that the first experiences with the drug are successful and a complete understanding of its efficacy and safety can be built. As experience accumulates, use can then be extended strictly and individually to more difficult patients within the approved indication.

Beyond patients who fall outside RCT eligibility criteria, patients with brain metastases are another special population that deserves close attention in SCLC practice, and several studies including DeLLphi-300, 301, and 304 have enrolled such patients. A post hoc analysis of DeLLphi-304 showed that, compared with chemotherapy, tarlatamab significantly reduced the risk of CNS progression or death by 46% (HR 0.54, 95% CI 0.39–0.75), with median CNS-PFS not estimable versus 7.2 months. Among patients with baseline brain metastases, median OS in the tarlatamab arm was 13.9 months, superior not only to 6.8 months with chemotherapy (HR 0.51, 95% CI 0.34–0.74) but also close to the 13.6 months seen in patients without brain metastases, indicating that the therapy can effectively improve survival outcomes in patients with ES-SCLC and brain metastases. Real-world studies further show that tarlatamab combined with radiotherapy is well tolerated, with no delayed CRS or ICANS after dose escalation, and that local radiotherapy for oligoprogression allows patients to continue treatment.

Drawing on his own clinical experience, Prof. Qin Haifeng notes that patients with brain metastases can generally benefit from tarlatamab whether or not they have previously received cranial radiotherapy, and that the drug does not appear to increase the risk of ICANS. Before treatment, however, brain MRI and neurological assessment should be completed, and symptomatic or progressive intracranial disease should be controlled with radiotherapy first before a TCE is started. He also proposes an approach for oligoprogression: when systemic disease is controlled and only a few sites are progressing, stereotactic radiotherapy can be used to treat those sites and tarlatamab continued, rather than switching systemic therapy in haste. Prof. Liu Xiaoqing also favors stratified management of patients with brain metastases: those who are symptomatic with marked brain edema should receive radiotherapy first, while asymptomatic patients with mild edema, good general condition, and no high-risk features may be cautiously treated with full informed consent and close monitoring. She summarizes the principle as steady advancement — neither rushing to use a new drug indiscriminately out of enthusiasm for innovation, nor letting concern deprive a patient who could benefit from access to tarlatamab.

Closing the Experience Gap With Consensus

After tarlatamab was approved in China, clinicians quickly found themselves in a position of not knowing how to use it and not daring to use it, with experience concentrated in leading hospitals. Disseminating that experience evenly to grassroots practice became the key task. Prof. Liu Xiaoqing notes that the Chinese expert consensus on DLL3-TCE therapy for SCLC was developed by more than 50 experts from medical oncology, radiation oncology, respiratory medicine, hematology, and other disciplines, producing ten recommendations covering clinical application and adverse event management, and was released in step with the 2026 CSCO SCLC guidelines, so that tarlatamab had guidance from the moment it reached the market. International experience likewise shows that standardized collaboration and multidisciplinary training are prerequisites for uniform practice. The consensus integrates global registrational evidence, Chinese bridging data, and domestic investigator-initiated trial and real-world experience, and calibrates them to Chinese practice in light of the high uptake of first-line immunotherapy, the high proportion of patients with brain metastases, and the heavy burden of comorbidities, establishing a single yardstick for clinical use.

Prof. Liu Xiaoqing stresses that the value of a consensus lies not only in listing recommendations, but in converting the experience concentrated in leading hospitals into a standard that all physicians can follow. China is vast and standards of care vary; if a new drug remains confined to a few centers, access is meaningless. The role of the expert committee is precisely to combine global evidence with the characteristics of Chinese patients through local calibration, forming a unified and executable standard, advancing standardized and uniform practice, and offering a replicable model for future TCEs and antibody-drug conjugates, while accumulating Chinese data and giving Chinese practice a voice. She emphasizes that a consensus is not an endpoint; it will be revised as evidence and experience evolve, and complex-case experience will be pushed down to grassroots practice through capacity building and online channels.

Prof. Qin Haifeng believes the key to implementing a consensus is turning paper recommendations into in-hospital workflow. He suggests establishing a multidisciplinary mechanism led by medical oncology with participation from critical care, neurology, imaging, pharmacy, and nursing, embedding grading and management of CRS and ICANS, ICE assessment, and criteria for discontinuation and restart into standard operating procedures, and setting up dedicated monitoring and referral pathways for the first cycle, so that there is a defined pathway for any event at any point in the patient journey. He also advocates shared physician-patient management across the whole course, with full disclosure before treatment and close follow-up during it. In his view, competition among new drugs ultimately concerns not only efficacy and safety but management capability: only when workflows and teams are in place can a drug's value translate reliably into real benefit for patients.

Summary: Moving Forward Together With TCE

The clinical value of tarlatamab has been established by the evidence from the DeLLphi registrational program and continues to be extended and corroborated in real-world studies and clinical practice. But moving from being able to use the drug to using it well and managing it safely still leaves many clinical questions in China for local investigators to answer through research and practice. We look forward to more lung cancer clinicians using TCE as a connection point to use tarlatamab in a standardized way, manage it safely, and study it in depth, so that more patients with SCLC benefit from innovative therapy.

Expert Profiles

References

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