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.
Poziotinib in Non–Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial
Author(s): Xiuning Le 1, Robin Cornelissen 2, Marina Garassino 3, Jeffrey M Clarke 4, Nishan Tchekmedyian 5, Jonathan W Goldman 6, Szu-Yun Leu 7, Gajanan Bhat 7, Francois Lebel 7, John V Heymach 1, Mark A Socinski 8
Source: J Clin Oncol. 2022 Mar 1;40(7):710-718. doi: 10.1200/JCO.21.01323. Epub 2021 Nov 29.
Dr. Lucio Gordan's Thoughts
Importance of NGS testing cannot be overemphasized. Besides poziotinib (which has very reasonable clinical benefit), anti-HER2 combination therapy may be of value in this patient population. Studies are ongoing. Poziotinib-related rash and diarrhea are manageable with proper understanding and interventions.
PURPOSE
Insertion mutations in Erb-b2 receptor tyrosine kinase 2 gene (ERBB2 or HER2) exon 20 occur in 2%-5% of non–small-cell lung cancers (NSCLCs) and function as an oncogenic driver. Poziotinib, a tyrosine kinase inhibitor, was evaluated in previously treated patients with NSCLC with HER2 exon 20 insertions.
METHODS
ZENITH20, a multicenter, multicohort, open-label phase II study, evaluated poziotinib in patients with advanced or metastatic NSCLC. In cohort 2, patients received poziotinib (16 mg) once daily. The primary end point was objective response rate evaluated by independent review committee (RECIST v1.1); secondary outcome measures were disease control rate, duration of response, progression-free survival, and safety and tolerability. Quality of life was assessed.
RESULTS
Between October 2017 and March 2021, 90 patients with a median of two prior lines of therapy (range, 1-6) were treated. With a median follow-up of 9.0 months, objective response rate was 27.8% (95% CI, 18.9 to 38.2); 25 of 90 patients achieved a partial response. Disease control rate was 70.0% (95% CI, 59.4 to 79.2). Most patients (74%) had tumor reduction (median reduction 22%). Median progression-free survival was 5.5 months (95% CI, 3.9 to 5.8); median duration of response was 5.1 months (95% CI, 4.2 to 5.5). Clinical benefit was seen regardless of lines and types of prior therapy, presence of central nervous system metastasis, and types of HER2 mutations. Grade 3 or higher treatment-related adverse events included rash (48.9%), diarrhea (25.6%), and stomatitis (24.4%). Most patients had poziotinib dose reductions (76.7%), with median relative dose intensity of 71.5%. Permanent treatment discontinuation because of treatment-related adverse events occurred in 13.3% of patients.
CONCLUSION
Poziotinib demonstrates antitumor activity in previously treated patients with HER2 exon 20 insertion NSCLC.
Author Affiliations
1Department of Thoracic Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX.2Medical Oncology, Erasmus University Medical Center, Rotterdam, the Netherlands.3Medical Thoracic Oncology, Istituto Nazionale dei Tumori di Milano-Fondazione IRCCS, Milan, Italy.4Medical Oncology, Duke University Medical Center, Durham, NC.5Medical Oncology, Pacific Shores Medical Group, Irvine, CA.6David Geffen School of Medicine at UCLA, Los Angeles, CA.7Research and Development, Spectrum Pharmaceuticals, Irvine, CA.8Thoracic Oncology, AdventHealth Cancer Institute, Orlando, FL.Related Articles
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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.
Lung Cancer Diagnosed Through Screening, Lung Nodule, and Neither Program: A Prospective Observational Study of the Detecting Early Lung Cancer (DELUGE) in the Mississippi Delta Cohort
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.
Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer
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.
