Recent clinical and regulatory developments are establishing immunotherapy as a cornerstone in treating small cell lung cancer (SCLC), offering renewed hope for improved outcomes in both limited and extensive-stage disease. These advancements include the use of durvalumab as consolidation therapy in limited-stage SCLC (LS-SCLC) and the FDA approval of tarlatamab-dlle for extensive-stage SCLC (ES-SCLC). Emerging antibody-drug conjugates (ADCs) are also generating interest among clinicians.
Durvalumab in Limited-Stage SCLC
The phase 3 ADRIATIC trial has demonstrated that consolidation treatment with durvalumab after concurrent platinum-based chemoradiotherapy significantly improves survival in patients with LS-SCLC. The study, presented at the 2024 ASCO Annual Meeting, showed a median overall survival (OS) of 55.9 months in patients treated with durvalumab compared to 33 months in those receiving placebo (HR, 0.73; 95% CI, 0.57-0.93; P = .0104). Progression-free survival (PFS) also improved, with a median PFS of 16.6 months with durvalumab versus 9.2 months with placebo (HR, 0.76; 95% CI, 0.61-0.95; P = .0161).
According to Dr. David R. Spigel, chief scientific officer at the Sarah Cannon Research Institute, "The ADRIATIC study has changed the standard of care and now includes subsequent durvalumab immunotherapy after the completion of concurrent chemoradiation."
Tarlatamab-dlle Approval for Extensive-Stage SCLC
Tarlatamab-dlle (Imdelltra), a bispecific T-cell engager (BiTE) targeting delta-like ligand 3 (DLL3) and CD3, received accelerated FDA approval on May 16, 2024, for patients with SCLC whose disease has progressed on or after platinum-based chemotherapy. This approval was based on findings from the phase 2 DeLLphi-301 trial, which demonstrated an objective response rate of 40% in heavily pretreated patients.
Dr. Alissa J. Cooper, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, noted, "In heavily pretreated patients, the response rate was 40%. But what was even more important was that some patients achieved a durable response that was ongoing at 12 months."
Antibody-Drug Conjugates: Emerging Therapies
Several antibody-drug conjugates (ADCs) are under investigation for SCLC treatment. ABBV-706, an ADC, is being evaluated in a phase 1 dose escalation study. Preliminary findings presented at the 2024 ASCO Annual Meeting showed a confirmed objective response rate of 40% in patients with SCLC. GSK5764227 (GSK227; HS-20093), another ADC, received breakthrough therapy designation from the FDA, with early data showing tumor shrinkage in 96.2% of patients with evaluable targeted lesions.
Challenges and Future Directions
Despite these advances, significant unmet needs remain in SCLC treatment, particularly in achieving durable remissions and cures. As Dr. Taofeek K. Owonikoko, executive director of the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, stated, "We are beginning to move ahead from wanting to just turn cancer into a chronic illness to trying to cure it."
Ongoing research is focused on optimizing the duration of immunotherapy, exploring novel combinations, and developing strategies to overcome treatment resistance. The integration of these advances into clinical practice promises to improve outcomes for patients with SCLC.
