Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non–Small-Cell Lung Cancer
Targeted therapy in NSCLC, FCS was part of this trial.
Human epidermal growth factor receptor 2 (HER2)–targeted therapies have not been approved for patients with non–small-cell lung cancer (NSCLC). The efficacy and safety of trastuzumab deruxtecan (formerly DS-8201), a HER2 antibody–drug conjugate, in patients with HER2-mutant NSCLC have not been investigated extensively.
We conducted a multicenter, international, phase 2 study in which trastuzumab deruxtecan (6.4 mg per kilogram of body weight) was administered to patients who had metastatic HER2-mutant NSCLC that was refractory to standard treatment. The primary outcome was objective response as assessed by independent central review. Secondary outcomes included the duration of response, progression-free survival, overall survival, and safety. Biomarkers of HER2 alterations were assessed.
A total of 91 patients were enrolled. The median duration of follow-up was 13.1 months (range, 0.7 to 29.1). Centrally confirmed objective response occurred in 55% of the patients (95% confidence interval [CI], 44 to 65). The median duration of response was 9.3 months (95% CI, 5.7 to 14.7). Median progression-free survival was 8.2 months (95% CI, 6.0 to 11.9), and median overall survival was 17.8 months (95% CI, 13.8 to 22.1). The safety profile was generally consistent with those from previous studies; grade 3 or higher drug-related adverse events occurred in 46% of patients, the most common event being neutropenia (in 19%). Adjudicated drug-related interstitial lung disease occurred in 26% of patients and resulted in death in 2 patients. Responses were observed across different HER2 mutation subtypes, as well as in patients with no detectable HER2 expression or HER2 amplification.
Trastuzumab deruxtecan showed durable anticancer activity in patients with previously treated HER2-mutant NSCLC. The safety profile included interstitial lung disease that was fatal in two cases. Observed toxic effects were generally consistent with those in previously reported studies. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Lung01 ClinicalTrials.gov number, NCT03505710. opens in new tab.)
Targeted therapy in NSCLC, FCS was part of this trial.
FCS medical oncologist and hematologist Lowell L. Hart, MD, FACP was first-author a study with FCS co-authors President and Managing Physician Lucio N. Gordan, MD, Director of Pharmacy Operations Kristen Boykin, Senior Vice President & Data Officer Trevor Heritage, PhD, and (Retired) Vice President of Pharmacy Services Ray Bailey BPharm, RPh, that evaluated ES-SCLC patients with chemotherapy-induced myelosuppression over a seven-year period, from January 2013 through December 2020. Within this cohort, 98% of the patients experienced at least one myelosuppressive episode following chemotherapy treatment, leading to the need for supportive care, creating additional costs in health care management and time lost in treatment for ES-SCLC.
Suddenly met-NSCLC is a crowded space. This study did not conclude that T+D+CT was better than D+CT, the findings showed that D+CT was better than CT alone. The addition of T to D+CT improved the PFS and OS trend but I don’t think this was a homerun result. There was not a significant OS benefit and further follow-up will declare these results. Also an improved outcomes were not seen in the non-squamous population. The pembrolizumab studies have 5+ years of follow-up and an improvement in PFS and OS across NSCLC subtypes.
Interesting study which the demonstrates the importance of prescriptive approach to detect NSCLC. Hopefully, in the future ctDNA may enhance or replace LDCT ability to detect patients with stage I/II disease.
This is a potential practice-changing study. Future data on overall-survival (OS) will be important to confirm results. Patient selection will also evolve over time especially in real-world practice. I presume more patients with stage II/III will get neoadjuvant therapy as opposed to a patient with a small lung nodule (stage I) taken to surgery, unless if there is significant OS for early stage patients as well.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
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