Sinonasal Squamous Cell Carcinoma

WEDNESDAY, Sept. 18, 2024 -- Neoadjuvant platinum-based chemotherapy improves structure preservation (SP) for patients with T3, T4a, and selected T4b resectable nasal and paranasal sinus squamous cell carcinoma (NPNSCC) requiring orbital or skull base resection, according to a study presented at the annual meeting of the European Society for Medical Oncology, held from Sept. 13 to 17 in Barcelona, Spain. Nabil F. Saba, M.D., from Winship Cancer Institute of Emory University in Atlanta, and colleagues reported the SP analysis in a study involving patients with T3, T4a, and selected T4b resectable NPNSCC. Participants were randomly allocated to receive surgery followed by postoperative radiation therapy of 60 Gy (standard arm) or the same treatment preceded by three cycles of neoadjuvant docetaxel 75 mg/m 2 and cisplatin 75 mg/m 2 (experimental arm). The SP rate and overall survival were the co-primary objectives. After enrolling 29 patients, the study was closed due to slow accrual in November 2023. The researchers found that the overall SP rate was 32 percent among 22 evaluable patients, with rates of 15 and 56 percent in the standard arm and experimental arm, respectively. The overall orbit preservation rate was 55 percent, with rates of 46 and 67 percent in the standard and experimental arms, respectively. The overall skull base preservation rate was 55 percent, with rates of 38 and 78 percent, respectively, in the standard and experimental arms. "Despite being unable to complete the planned accrual and reach a definitive answer, the study results are striking and support the use of neoadjuvant chemotherapy as an intervention that could improve the chance of organ preservation for these patients," Saba said in a statement. Press Release More Information Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

The Breakthrough Therapy Designation is based on data from a Phase I trial of JNJ-6372 alone and in combination with lazertinib, a novel third-generation EGFR TKI in adults with advanced NSCLC. The Janssen Pharmaceutical , a Johnson & Johnson company, reported the U.S. Food and Drug Administration (FDA) granted its JNJ-6372 Breakthrough Therapy Designation. The drug is being developed for metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) Exon 20 insertion mutations where the disease has progressed while the patient is on or after receiving platinum-based chemotherapy. Breakthrough Therapy Designation is designed to speed the development and regulatory review of drugs for serious or life-threatening diseases. It is based on preliminary clinical data showing the drug might have substantial improvement on at least one clinically significant endpoint over available therapy. NSCLC and EGFR Exon 20 insertion mutation cancers do not typically respond to EGFR tyrosine kinase inhibitors (TKI)s and have a worse prognosis compared to patients with more common EGFR mutations. JNJ-6372 is an EGFR-MET bispecific antibody that targets activating and resistant EGFR and MET mutations and amplifications. It came out of a licensing deal with Genmab for use of its DuoBody technology platform. Janssen also collaborated with Genmab on its Darzalex (daratumumab), a blockbuster drug for multiple myeloma, and its follow-up HexaBody-CD38. hbspt.cta.load(4413123, '4e87abe9-779b-4c65-98dd-ea451779faa9', {}); The Breakthrough Therapy Designation is based on data from a Phase I trial of JNJ-6372 alone and in combination with lazertinib, a novel third-generation EGFR TKI in adults with advanced NSCLC. Currently the company is enrolling Part 2 dose expansion cohorts as the study is now evaluating the drug as a monotherapy in multiple NSCLC sub-populations with specific genetic changes like those with C797S resistance mutation or MET amplification. Lazertinib is a third-generation EGFR inhibitor that Janssen licensed from Korea’s Yuhan Corp in 2018 for $50 million up front and up to $1.25 billion in possible milestone payments. “JNJ-6372 is a novel bispecific antibody that we believe has the potential to benefit patients with Exon 20 mutation insertions who often do not respond to currently available oral EGFR-targeted or immune checkpoint inhibitor therapies,” said Peter Lebowitz, Global Therapeutic Area Head, Oncology, Janssen Research & Development. “This Breakthrough Therapy Designation is a significant milestone in our ongoing efforts to advance JNJ-6372 in clinical development and target genetically-defined lung cancer.” EGFR exon 20 insertions have been reported in 4% to 10% of all cases of EGFR-mutated NSCLC, as well as in other cancers including a rare head and neck cancer called sinonasal squamous cell carcinoma (SNSCC). These types of mutated cancers do not typically respond to treatment with first- and second-generation EGFR inhibitors like AstraZeneca’s Iressa (gefitinib), Roche’s Tarceva (erlotinib) and Boehringer Ingelheim’s Giotrif (afatinib). They also do not seem to respond to immunotherapies like checkpoint inhibitors. In 2019, Spectrum Pharmaceuticals provided data for its third-generation therapy poziotinib in EGFR exon 20 insertion mutation-positive NSCLCs but did not receive Breakthrough Therapy Designation from the FDA. The company expects to report more data from a Phase II trial in 2022. Lung cancer is the second most common cancer in men and women in the U.S., after skin cancer. NSCLC accounts for 80% to 85% of all lung cancers. The primary subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.