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Clinical Trial
. 2024 Jun 15;154(12):2142-2150.
doi: 10.1002/ijc.34894. Epub 2024 Mar 6.

Efficacy of ramucirumab combination chemotherapy as second-line treatment in patients with advanced adenocarcinoma of the stomach or gastroesophageal junction after exposure to checkpoint inhibitors and chemotherapy as first-line therapy

Michael Masetti  1 , Salah-Eddin Al-Batran  2 , Thorsten O Goetze  2 , Peter Thuss-Patience  3 , Jorge Riera Knorrenschild  4 , Eray Goekkurt  5 , Gunnar Folprecht  6 , Thomas Jens Ettrich  7 , Udo Lindig  8 , Kim Barbara Luley  9 , Daniel Pink  10 , Tobias Dechow  11 , Disorn Sookthai  12 , Sabine Junge  12 , Maria Loose  12 , Claudia Pauligk  12 , Sylvie Lorenzen  1
Affiliations
Clinical Trial

Efficacy of ramucirumab combination chemotherapy as second-line treatment in patients with advanced adenocarcinoma of the stomach or gastroesophageal junction after exposure to checkpoint inhibitors and chemotherapy as first-line therapy

Michael Masetti et al. Int J Cancer. .

Abstract

FOLFOX plus nivolumab represents a standard of care for first-line therapy of advanced gastroesophageal cancer (aGEC) with positive PD-L1 expression. The efficacy of second-line VEGFR-2 inhibition with ramucirumab (RAM) plus chemotherapy after progression to immunochemotherapy remains unclear. Medical records of patients with aGEC enrolled in the randomized phase II AIO-STO-0417 trial after treatment failure to first-line FOLFOX plus nivolumab and ipilimumab were retrospectively analyzed. Patients were divided into two groups based on second-line therapy: RAM plus chemotherapy (RAM group) or treatment without RAM (control group). Eighty three patients were included. In the overall population, progression-free survival (PFS) in the RAM group was superior to the control (4.5 vs 2.9 months). Responders (CR/PR) to first-line immunochemotherapy receiving RAM containing second-line therapy had prolonged OS from start of first-line therapy (28.9 vs 16.5 months), as well as second-line OS (9.6 vs 7.5 months), PFS (5.6 vs 2.9 months) and DCR (53% vs 29%) compared to the control. PD-L1 CPS ≥1 was 42% and 44% for the RAM and the control, respectively. Patients with CPS ≥1 in the RAM group showed better tumor control (ORR 25% vs 10%) and improved survival (total OS 11.5 vs 8.0 months; second-line OS 6.5 vs 3.9 months; PFS 4.5 vs 1.6 months) compared to the control. Prior exposure to first-line FOLFOX plus dual checkpoint inhibition followed by RAM plus chemotherapy shows favorable response and survival rates especially in patients with initial response and positive PD-L1 expression and has the potential to advance the treatment paradigm in aGEC.

Keywords: antiangiogenic treatment; anti‐VEGFR‐2 therapy; gastroesophageal cancer; immunotherapy; ramucirumab.

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