Editor’s Note:
The ESMO Annual Meeting in 2023 was held grandly in Madrid, Spain, from October 20th to 24th. As an authoritative annual event in the field of oncology, the conference announces many cutting-edge academic advances in oncology each year. This year, Chinese scholars have performed prominently at the conference, with many domestic experts having their posters or oral presentations selected. Professor Fei Han from the Cancer Prevention and Treatment Center of Sun Yat-sen University has two outstanding research results included in this conference. Professor Fei Han was interviewed on-site, providing insights into the current research progress on nasopharyngeal carcinoma (NPC) in China.
920P – Envafolimab plus chemoradiotherapy for locally advanced nasopharyngeal carcinoma (NPC), a prospective, single-armed phase II trial
▌Background
The combination of gemcitabine and cisplatin (GP) before concurrent chemoradiotherapy (CCRT) has shown good survival outcomes and acceptable toxicity in patients with locally advanced nasopharyngeal carcinoma (LANPC). Immune checkpoint blockade therapy with GP has been shown to improve the survival of recurrent or metastatic nasopharyngeal carcinoma. We aimed to evaluate the efficacy and safety of camrelizumab (PD-L1) combined with definitive chemoradiotherapy in previously untreated LANPC.
▌Methods
In this single-arm phase 2 study, eligible patients aged 18-65 with non-keratinizing LANPC staged TxN2-3M0 or T4N1M0 (AJCC 8th) were enrolled. Patients received 3 cycles of intravenous gemcitabine (1000 mg/m2, d1/8, Q3W) + cisplatin (80 mg/m2, d1, Q3W), combined with subcutaneous camrelizumab (300 mg, d1, Q3W) for induction chemotherapy. Subsequently, CCRT was performed, and during this period, each patient received 2 cycles of cisplatin (100 mg/m2, d1, Q3W) + camrelizumab (300 mg, d1, Q3W). Maintenance treatment with camrelizumab (300 mg, d1, Q3W) was continued for one year until disease progression or intolerance. The primary endpoint was 3-year progression-free survival, and secondary endpoints included objective response rate (ORR), disease control rate (DCR), local-regional progression-free survival, distant metastasis-free survival, and toxicity. All enrolled patients have completed induction chemotherapy, and the study is ongoing.
▌Results
From June 14, 2022, to December 13, 2022, a total of 36 patients were enrolled at the Cancer Center of Sun Yat-sen University (median age 44 years, 63.9% male). As of May 4, 2023, with a median follow-up of 7.38 months, the ORR and DCR were 94.4% (95% confidence interval: 81.3%, 99.3%) and 97.2% (95% confidence interval: 85.5%, 99.9%), respectively. Compared to standard regimens, the use of camrelizumab in combination did not increase the incidence of hematologic toxicity events, and no grade 3/4 immune-related adverse events (irAEs) were observed. Long-term efficacy awaits further observation.
▌Conclusion
Camrelizumab plus chemoradiotherapy is effective and safe for the treatment of LANPC, and further follow-up is needed to confirm long-term efficacy.
Researcher’s Comments
“Due to the pandemic, we haven’t attended the ESMO conference for several years. The focus of the European Society for Medical Oncology (ESMO) is always on the advances in internal medicine, and this year’s conference impressed me with the development of many new drugs and innovative applications of existing drugs in oncology.
Nasopharyngeal carcinoma is a cancer with Chinese characteristics, and the previous treatment outcomes have been quite remarkable. Currently, we are seeking new breakthroughs in the treatment of some advanced nasopharyngeal cancers, such as N2, N3, or T4-stage patients. These patients are known to have a higher risk of recurrence and metastasis, leading to suboptimal overall survival.
With the advent of PD-1/PD-L1 immune therapy, many PD-L1 drugs have shown good efficacy in the clinical treatment of various cancers. The application of PD-L1 drugs in nasopharyngeal carcinoma has achieved an efficacy rate of over 94%, with a DCR reaching 97%. The efficacy is remarkable, making the use of PD-L1 drugs in locally advanced nasopharyngeal carcinoma highly anticipated. Additionally, as PD-L1 drugs are administered via subcutaneous injection, patients almost do not need lengthy intravenous infusions or hospitalization. Our ongoing clinical study has provided preliminary results, and overall, the side effects are manageable, and patients show excellent efficacy. We look forward to further updates on long-term results in the future, which can better guide the clinical application for advanced nasopharyngeal cancer patients.”
860MO – MRG003: A novel EGFR-targeted antibody-drug conjugant (ADC) for recurrent/metastatic nasopharyngeal carcinoma
▌Background
The need for more effective treatment after chemotherapy and immunotherapy for recurrent/metastatic nasopharyngeal carcinoma (r/m NPC) has not been met. MRG003 is a novel ADC composed of a humanized anti-EGFR monoclonal antibody conjugated to MMAE via a VC linker. This study reports the main dose-finding results of MRG003 in r/m NPC.
▌Methods
This was a phase IIa study aiming to evaluate the safety and efficacy of MRG003 in pathologically confirmed r/m NPC patients who had failed prior platinum-based and/or PD-L1 therapies. The study investigated two dose levels of MRG003 (2.0 or 2.3 mg/kg, Q3W) to determine the optimal dose. The primary endpoint was the objective response rate (ORR) according to RECIST 1.1. Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and safety.
▌Results
A total of 61 patients received at least one cycle of MRG003, with 30 patients receiving 2.0 mg/kg (DL1) and 31 patients receiving 2.3 mg/kg (DL2). Most patients (52/61) had received ≥2 lines of previous treatment, and 53 patients (86.9%) had received platinum and PD-1/L1 therapy. As of the data cutoff date (March 15, 2023), 28 evaluable patients in the DL1 cohort had an ORR and DCR of 39.3% and 71.4%, respectively. In the DL2 cohort, 29 evaluable patients had an ORR and DCR of 55.2% and 86.2%, respectively. The median duration of response (mDoR) for DL1 was 6.8 months (95% CI: 5.7, 16.3), and for DL2, it was 6.8 months (95% CI: 2.9, 9.8). The median PFS (mPFS) for DL1 was 7.3 months (95% CI: 2.9, 9.7), while DL2 was not mature. The most commonly reported treatment-related adverse events (TRAEs) were rash (49.2%), itching (41.0%), anemia (34.4%), and hair loss (31.1%); most TRAEs were grade 1 or 2 according to CTCAE 5.0. The incidence of treatment-related serious adverse events (SAEs) was 11.5% (7/61). The dose reduction rate due to TRAEs was 13.1% (8/61), and treatment discontinuation occurred in 3 cases (4.9%). No treatment-related deaths were observed.
▌Conclusion
MRG003 shows promising antitumor activity in advanced r/m nasopharyngeal cancer patients, with acceptable tolerability and controllable safety. Based on the numerically higher ORR, 2.3 mg/kg may have better efficacy, tolerability, and safety, recommending it for further crucial research.
Researcher’s Comments
“The research on nasopharyngeal carcinoma is currently flourishing in China, with different units proposing many new ideas to address the clinical difficulties encountered: one is local recurrence, and the other is distant metastasis. Our team’s main goal is still the treatment of locally recurrent nasopharyngeal carcinoma. In the future, it may involve new research drugs such as biologic therapy and immunotherapy, hoping to effectively improve patient survival.
Although our research may still be lacking in some basic aspects, we have made some breakthroughs in clinical aspects. An oral presentation on an EGFR ADC drug at the conference showed higher efficacy than PD-1/PD-L1 drugs, and it may be a highly anticipated new drug in the future. If its efficacy in recurrent metastatic nasopharyngeal cancer patients is further clarified in future phase III clinical trials, it may be applied to the clinical treatment of advanced nasopharyngeal cancer in the future.”
Cancer Prevention and Treatment Center, Sun Yat-sen University
Chief Physician, Doctor of Medicine, Doctoral Supervisor
Deputy Director of Radiotherapy Department, Cancer Prevention and Treatment Center, Sun Yat-sen University
Visiting Scholar, Stanford University Hospital, USA
Chairman of the Radiotherapy Professional Committee, Guangdong Anti-Cancer Association
Deputy Leader of the Biology Group, Radiation Oncology Treatment Branch, Chinese Medical Association
Deputy Director of the Expert Committee on Laryngeal Cancer Quality Control, National Tumor Quality Control Center
Executive Committee Member, Head and Neck Tumor Expert Committee, Chinese Society of Clinical Oncology
Executive Committee Member, Radiation Protection Professional Committee, Chinese Anti-Cancer Association
Secretary-General, Pearl River Delta Regional Radiotherapy Collaboration Group
Director, 5th Council of Guangdong Anti-Cancer Association
Deputy Director, Radiation Professional Committee, Guangdong Clinical Medical Association
