Vanesa Gutiérrez Calderón

BACKGROUND: (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC). METHODS: -mutated (exon 19 deletion or L858R), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib (in an open-label fashion), osimertinib (in a blinded fashion), or lazertinib (in a blinded fashion, to assess the contribution of treatment components). The primary end point was progression-free survival in the amivantamab-lazertinib group as compared with the osimertinib group, as assessed by blinded independent central review. RESULTS: -related toxic effects. The incidence of discontinuation of all agents due to treatment-related adverse events was 10% with amivantamab-lazertinib and 3% with osimertinib. CONCLUSIONS: -mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).

BACKGROUND: (epidermal growth factor receptor)-mutated advanced non-small-cell lung cancer (NSCLC) was significantly improved with amivantamab-lazertinib as compared with osimertinib. Results of the protocol-specified final overall survival analysis in this trial have not been reported. METHODS: -mutated (exon 19 deletion or L858R substitution), locally advanced or metastatic NSCLC to receive amivantamab-lazertinib, osimertinib, or lazertinib. Overall survival (assessed in an analysis of the time from randomization to death from any cause) in the amivantamab-lazertinib group as compared with the osimertinib group was a key secondary end point. Additional end points included safety. RESULTS: A total of 429 participants each were assigned to receive amivantamab-lazertinib or osimertinib. Over a median follow-up of 37.8 months, amivantamab-lazertinib led to significantly longer overall survival than osimertinib (hazard ratio for death, 0.75; 95% confidence interval, 0.61 to 0.92; P = 0.005); 3-year overall survival was 60% and 51%, respectively. At the clinical cutoff date, 38% of participants in the amivantamab-lazertinib group and 28% in the osimertinib group were still receiving the assigned treatment. Adverse events of grade 3 or higher were more common with amivantamab-lazertinib (in 80% of participants) than with osimertinib (in 52%), particularly skin-related events, venous thromboembolism, and infusion-related events; these findings were consistent with the established safety profile of each treatment. No new safety signals were observed with additional follow-up. CONCLUSIONS: -mutated advanced NSCLC than osimertinib but was associated with an increased risk of adverse events of grade 3 or higher. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).

PURPOSE The phase III RESILIENT trial compared second-line liposomal irinotecan with topotecan in patients with small cell lung cancer (SCLC). PATIENTS AND METHODS Patients with SCLC and progression on or after first-line platinum-based chemotherapy were randomly assigned (1:1) to intravenous (IV) liposomal irinotecan (70 mg/m 2 every 2 weeks in a 6-week cycle) or IV topotecan (1.5 mg/m 2 daily for 5 consecutive days, every 3 weeks in a 6-week cycle). The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) and objective response rate (ORR). RESULTS Among 461 randomly assigned patients, 229 received liposomal irinotecan and 232 received topotecan. The median follow-up was 18.4 months. The median OS was 7.9 months with liposomal irinotecan versus 8.3 months with topotecan (hazard ratio [HR], 1.11 [95% CI, 0.90 to 1.37]; P = .31). The median PFS per blinded independent central review (BICR) was 4.0 months with liposomal irinotecan and 3.3 months with topotecan (HR, 0.96 [95% CI, 0.77 to 1.20]; nominal P = .71); ORR per BICR was 44.1% (95% CI, 37.6 to 50.8) and 21.6% (16.4 to 27.4), respectively. Overall, 42.0% and 83.4% of patients receiving liposomal irinotecan and topotecan, respectively, experienced grade ≥3 related treatment-emergent adverse events (TEAEs). The most common grade ≥3 related TEAEs were diarrhea (13.7%), neutropenia (8.0%), and decreased neutrophil count (4.4%) with liposomal irinotecan and neutropenia (51.6%), anemia (30.9%), and leukopenia (29.1%) with topotecan. CONCLUSION Liposomal irinotecan and topotecan demonstrated similar median OS and PFS in patients with relapsed SCLC. Although the primary end point of OS was not met, liposomal irinotecan demonstrated a higher ORR than topotecan. The safety profile of liposomal irinotecan was consistent with its known safety profile; no new safety concerns emerged.

BACKGROUND: RESILIENT (NCT03088813) is a phase 2/3 study assessing the safety, tolerability, and efficacy of liposomal irinotecan monotherapy in patients with small cell lung cancer and disease progression on/after first-line platinum-based therapy. Here, we present results from RESILIENT part 1. METHODS: This open-label, single-arm, safety run-in evaluation with dose-exploration and dose-expansion phases included patients ≥18 years old with Eastern Cooperative Oncology Group performance status of 0/1; those with asymptomatic central nervous system metastases were eligible. The primary objectives were to evaluate safety and tolerability and recommend a dose for further development. Efficacy end points were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: . Of these 25 patients (median age [range], 59.0 [48.0-73.0] years, 92.0% with metastatic disease), 10 experienced grade ≥3 treatment-related treatment-emergent adverse events (TEAEs), most commonly diarrhea (20.0%) and neutropenia (16.0%), and 3 had serious treatment-related TEAEs, of whom 2 died. ORR was 44.0% (95% confidence interval [CI]: 24.40-65.07; 1 complete response, 10 partial responses) and median (95% CI) PFS and OS were 3.98 (1.45-4.24) months and 8.08 (5.16-9.82) months, respectively. CONCLUSION: Overall, no new safety signals were identified with liposomal irinotecan, and antitumor activity was promising. RESILIENT part 2, a randomized, controlled, phase 3 study of liposomal irinotecan versus topotecan, is ongoing. LAY SUMMARY: Small cell lung cancer (SCLC) is an aggressive disease with few treatment options after platinum-based therapy. Administering 1 option, irinotecan, as a "liposomal" formulation, may extend drug exposure and improve outcomes. The RESILIENT part 1 trial assessed the safety and efficacy of liposomal irinotecan in 25 adults with SCLC after disease progression despite platinum-based therapy. No new safety concerns were reported. The most common moderate-to-severe side effects were diarrhea (20% of patients) and neutropenia (16%). Tumors responded to treatment in 44% of patients. Average survival was 8.08 months, and time to disease progression was 3.98 months. Liposomal irinotecan trials are ongoing.