Trastuzumab deruxtecan (T-DXd) demonstrated strong and durable responses in patients with previously treated human epidermal growth factor receptor 2 (HER2;ERBB2)-mutant (HER2m) metastatic non-small cell lung cancer (mNSCLC) in the DESTINY-Lung02 primary analysis (December 23, 2022, data cutoff). This final analysis evaluated T-DXd efficacy and safety after 8 additional months of follow-up, including clinically relevant subgroups and patient-reported outcomes. DESTINY-Lung02 was a randomized, dose-blinded, multicenter, phase 2 trial. Patients with previously treated HER2m mNSCLC were randomized 2:1 to receive T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. Primary endpoint was confirmed objective response rate (cORR) by blinded independent central review. As of August 25, 2023, 102 and 50 patients had received T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up (Q1-Q3) was 15.8 months (8.2-20.7) and 16.5 months (9.4-20.8). cORR (95% CI) was 50.0% (51/102; 39.9%-60.1%) and 56.0% (28/50; 41.3%-70.0%). Safety profile was acceptable and generally manageable. Median treatment duration (Q1-Q3) was 7.7 months (3.7-14.4) and 8.3 months (2.8-13.1); drug-related grade ≥3 treatment-emergent adverse events occurred in 39.6% (40/101) and 60.0% (30/50), with nausea most common (67.3% [68/101], 82.0% [41/50]). Adjudicated drug-related interstitial lung disease (ILD) occurred in 14.9% (15/101) and 32.0% (16/50), mostly grade 1/2; one grade 5 in each arm. Health-related quality of life (HRQoL) was preserved for the duration of T-DXd treatment while sample size was sufficient for analysis, with no adverse effects on HRQoL observed at either dose. T-DXd showed strong and durable responses at both doses, with no clinically significant changes in toxicity. The approved 5.4-mg/kg dose showed a more favorable benefit-risk profile, including lower adjudicated drug-related ILD incidence.

Background: The treatment of lung cancer has made dramatic progress in the past decade, but due to the high cost of drugs, the total pharmaceutical cost has been rising explosively. There are currently no data available in Japan on which regimens are used, to what extent they are used, and what their total cost is. Methods: Sixty Japanese centers belonging to the Lung Cancer Study Group of the Japan Clinical Oncology Group were surveyed for information about the first-line treatment for advanced lung cancer in practice from July 2021 to June 2022. Three types of cancer were included: driver gene mutation-negative NSCLC, EGFR mutation-positive NSCLC, and extensive-stage small cell lung cancer (ES-SCLC). Results: Recent treatment costs for ICIs or ICI plus chemotherapy were about 20–55 times higher than those for conventional chemotherapy. Of the 3738 patients with driver gene aberration-negative NSCLC, 2573 (68.8%) received treatments with monthly cost of 500 000 Japanese yen (JPY) or more; 2555 (68.4%) received ICI therapy. Of the 1486 patients with EGFR mutation-positive NSCLC, 1290 (86.8%) received treatments with a monthly cost of 500 000 JPY or more; 1207 (81.2%) received osimertinib. ICI treatments with a monthly cost of 500 000 JPY or more were administered to 607 (56.3%) of 1079 patients with ES-SCLC. Elderly NSCLC patients received slightly more high-cost treatment than younger patients. Conclusion: Recent treatments cost many times more than conventional chemotherapy. This study revealed that high-cost treatments were widely used in advanced lung cancer and some of high-cost treatments were used despite the lack of clear evidence. Physicians should pay attention to the cost of treatments they use.

Anti-programmed death 1 (PD-1) antibodies, a type of immune checkpoint inhibitor (ICI), have enhanced survival rates in non-small cell lung cancer (NSCLC).