Tarlatamab Reduces Symptom Burden and Treatment Side Effects in Extensive-Stage Small Cell Lung Cancer

Clinical Summary:

• Design/Population: DeLLphi-304 was a phase 3 trial comparing tarlatamab with standard-of-care chemotherapy in patients with extensive-stage small cell lung cancer whose disease had progressed during or after first-line platinum-based therapy.
• Key Outcomes: Tarlatamab delayed deterioration in dyspnea, cough, chest pain, and physical functioning compared with chemotherapy. At week 19, a greater proportion of patients receiving tarlatamab reported clinically meaningful symptom improvement. Treatment-related side-effect burden was also less persistent with tarlatamab.
• Clinical Relevance: These patient-reported findings extend the clinical benefit of tarlatamab beyond survival, strengthening its overall benefit-risk profile in this patient population. 

Patient-reported outcome data from the phase 3 DeLLphi-304 trial showed that tarlatamab improved symptom burden and delayed deterioration in multiple domains compared with standard-of-care chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease had progressed during or after first-line platinum-based treatment.

“ES-SCLC is associated with a high symptom burden and impaired health-related quality of life,” stated Giannis Mountzios, MD, Henry Dunant Hospital Center, Athens, Greece, and coauthors. “Capturing the patients’ perspective of their symptoms, functioning, and overall [health-related quality of life] is therefore essential, complementing the traditional efficacy and safety end points.” 

In this multicenter, open-label trial, 509 patients were randomized 1:1 to receive either tarlatamab (n = 254) or standard-of-care chemotherapy with topotecan, lurbinectedin, or amrubicin (n = 255). Tarlatamab was administered with a 1-mg step-up dose on day 1 of cycle 1, followed by 10 mg on days 8 and 15 of cycle 1 and then 10 mg every 2 weeks thereafter. 

Patient-reported outcomes were assessed using multiple validated instruments, including EORTC QLQ-C30, EORTC QLQ-LC13, FACT-G GP5, Brief Pain Inventory–Short Form, and EQ-5D-5L visual analogue scale. Analyses evaluated changes from baseline, response rates, and time to deterioration in symptoms functioning, and health-related quality of life. 

At week 19, a greater proportion of patients receiving tarlatamab achieved clinically meaningful improvement compared with chemotherapy in chest pain (19% vs 10%), cough (35% vs 26%), dyspnea (22% vs 7%), physical functioning (13% vs 8%), and global health status/quality of life (23% vs 15%). 

Tarlatamab also delayed deterioration in several key disease-related symptoms. Median time to deterioration in dyspnea was 38.6 weeks with tarlatamab compared with 17.9 weeks with chemotherapy, corresponding to a 47% reduction in the risk of deterioration. 

Median time to deterioration in cough was 66.1 weeks with tarlatamab compared with 31.7 weeks with chemotherapy. For chest pain, median time to deterioration was not estimable with tarlatamab compared with 48.3 weeks with chemotherapy. 

Physical functioning was also preserved longer with tarlatamab. Median time to deterioration was 35.7 weeks compared with 8.7 weeks with chemotherapy. Time to deterioration in global health status/quality of life was comparable between arms (2.6 weeks vs 4 weeks). 

Across additional symptom and functional domains, outcomes also tended to favor tarlatamab. At week 19, all functional scales favored tarlatamab over chemotherapy, while improvements were observed across 12 of 16 symptom scales. Significant between-group differences favored tarlatamab for diarrhea, dyspnea, insomnia, alopecia, fatigue, nausea, pain, and financial difficulties. 

Patient-reported treatment tolerability also favored tarlatamab. At week 19, 10.3% of patients receiving tarlatamab reported at least moderate bother from treatment side effects compared with 29.2% receiving chemotherapy. Side effect burden increased initially with both treatments, but declined after the first 3 weeks with tarlatamab while remaining elevated with chemotherapy.

These patient-reported findings complement the previously reported efficacy results from DeLLphi-304, in which tarlatamab improved overall survival (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.47 to 0.77; P < .001) and progression-free survival compared with standard-of-care chemotherapy. Grade ≥3 adverse events were also less frequent with tarlatamab (54% vs 80%).

“Collectively, these [patient-reported outcome] data further support the positive benefit–risk profile of tarlatamab and underscore its value in improving both efficacy and [health-related quality of life] in this patient population,” concluded Dr Mountzios et al. 

Source: 

Mountzios G, Lammers PE, Sun L, et al. Patient-reported outcomes with tarlatamab in extensive-stage small cell lung cancer after platinum-based chemotherapy: Results from the phase 3 DeLLphi-304 trial. Lung Cancer. Published online: August 13, 2026. doi: 10.1016/j.lungcan.2026.109581