Navigational Bronchoscopy or Transthoracic Needle Biopsy for Lung Nodules
Non-inferior in diagnosing malignant or benign lesions, and safer (less pneumothorax). The question remains about the amount of tissue for further testing.
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
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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FCS medical oncologist and hematologist Ernesto Bustinza-Linares, MD has co-authored an abstract published in the American Society of Clinical Oncology Journal, JCO Precision Oncology, that uncovers a new testing method to determine personalized care options for patients with metastatic non-small cell lung cancer (NSCLC). The abstract’s authors address the limitations of existing guidelines that recommend checkpoint immunotherapy, sometimes in combination with chemotherapy, for treating NSCLC, which often discounts patient variability and immune factors. The findings from the study show that by incorporating additional plasma proteome-based testing, combined with the standard protein inhibitor testing, clear differences in patient outcomes were observed after applying targeted treatments based on the testing results.
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Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study
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.