KEY TAKEAWAYS
- The CheckMate 648 Phase 3 study (NCT03143153) aimed to test the Efficacy and Safety of NIVO + chemotherapy and NIVO + IPI in previously untreated advanced ESCC patients.
- Advanced ESCC patients were assigned to chemotherapy, NIVO + IPI, or chemotherapy alone. BICR assessed OS and PFS.
- The study revealed that NIVO + chemo and NIVO + IPI show improved PFS2, prolonged DOR, and acceptable safety profiles in advanced ESCC, supporting their potential as the 1L standard of care.
In the phase 3 CheckMate 648 study, NIVO + chemotherapy and NIVO + IPI significantly improved overall survival (OS) compared to chemotherapy in previously untreated patients (pts) with advanced esophageal squamous cell carcinoma (ESCC). Researchers report extended findings from the primary analysis with a minimum of 13-month (mo) follow-up.
Patients with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC were randomized to receive either NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), or chemo. OS and progression-free survival (PFS) per blinded independent central review (BICR) in patients with tumor cell programmed death ligand 1 (PD-L1) ≥ 1% were the primary endpoints.
Planned secondary endpoints for hierarchical testing were OS, PFS, and objective response rate (ORR) according to BICR in all randomized patients. Exploratory endpoints included duration of response (DOR) per BICR and progression-free survival (PFS2) per investigator (time from randomization to progression after subsequent systemic therapy, initiation of second subsequent systemic therapy, or death).
PFS2 favored NIVO + chemo (HR 0.64, 95% CI 0.54–0.77) and NIVO + IPI (HR 0.74, 95% CI 0.62–0.88) vs. chemo among all patients randomized to NIVO + chemo (n = 321), NIVO + IPI (n = 325), or chemo (n = 324). ORR (95% CI) was 47% (range: 42–53), 28% (23–33), and 27% (22–32)). About 39% of responders to NIVO + chemo and 48% of responders to NIVO + IPI had DOR ≥12 months, compared to 23% of responders to chemotherapy. There will be a presentation of efficacy data by tumor cell PD-L1 and PD-L1 combined positive scores.
Non-endocrine selection TRAE soccurred in less than equal to 6% of pts with NIVO + chemo, and NIVO + IPI resolved in 57%–95% of patients across organ categories. The study revealed that NIVO + chemo and NIVO + IPI show improved PFS2, prolonged DOR, and acceptable safety profiles in advanced ESCC, supporting their potential as the 1L standard of care.
Source:https://meetings.asco.org/abstracts-presentations/211132
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03143153
Ian Chau, Jaffer A. Ajani, Yuichiro Doki, Jianming Xu, Lucjan Wyrwicz, Satoru Motoyama, Takashi Ogata, Hisato Kawakami, Chih-Hung Hsu, Antoine Adenis, Farid El Hajbi, Maria Di Bartolomeo, Maria Ignez Freitas Melro Braghiroli, Eva Holtved, Mariela A. Blum Murphy, Sandzhar Abdullaev, Samira Soleymani, Ming Lei, Ken Kato, Yuko Kitagawa/Nivolumab (NIVO) plus chemotherapy (chemo) or ipilimumab (IPI) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): Expanded efficacy and safety analyses from CheckMate 648/J Clin Oncol 40, 2022 (suppl 16; abstr 4035) DOI10.1200/JCO.2022.40.16_suppl.4035
