Preoperative Chemoradiotherapy for Resectable Gastric Cancer

Author(s): Trevor Leong, M.D., B. Mark Smithers, M.D., Michael Michael, M.D., Karin Haustermans, M.D., Rebecca Wong, M.D., Val Gebski, M.Stat., Rachel L. O’Connell, Ph.D., John Zalcberg, M.D., Alex Boussioutas, M.D., Michael Findlay, M.D., David Willis, M.Tech., Alisha Moore, B.Med.Rad.Sci., William K. Murray, M.D., Florian Lordick, M.D., Chris O’Callaghan, D.V.M., Ph.D., Carol Swallow, M.D., Gail Darling, M.D., Danielle Miller, M.P.H., Andrew Strickland, M.D., Moishe Liberman, M.D., Laurent Mineur, M.D., and John Simes, M.D. https://orcid.org/0000-0002-3740-7563, for the Australasian Gastro-Intestinal Trials Group, National Health and Medical Research Council Clinical Trials Centre, Trans-Tasman Radiation Oncology Group, European Organisation for Research and Treatment of Cancer, and Canadian Cancer Trials Group*
Source: DOI: 10.1056/NEJMoa2405195
Original Article
Professional photo of Anjan J Patel, MD

Dr. Anjan Patel's Thoughts

Preoperative chemoradiation added to perioperative chemotherapy (ECF/ECX or FLOT) was not beneficial.  Of note this study was done in a non-US, predominantly caucasian population. It seems XRT has less and less of a role in gastroesophageal junction / gastroesophageal (GEJ/GE) cancers.

BACKGROUND

In Western countries, the current standard of care for resectable gastric cancer is perioperative chemotherapy. Preoperative chemoradiotherapy has been considered, but data are limited regarding this treatment as compared with perioperative chemotherapy alone.

METHODS

We conducted an international, phase 3 trial in which patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive preoperative chemoradiotherapy plus perioperative chemotherapy or perioperative chemotherapy alone (control). In both groups, patients received either epirubicin, cisplatin, and fluorouracil or fluorouracil, leucovorin, oxaliplatin, and docetaxel both before and after surgery; the preoperative-chemoradiotherapy group also received chemoradiotherapy (45 Gy in 25 fractions of radiation, plus fluorouracil infusion). The primary end point was overall survival, and secondary end points included progression-free survival, pathological complete response, toxic effects, and quality of life.

RESULTS

A total of 574 patients underwent randomization at 70 sites in Australasia, Canada, and Europe: 286 to the preoperative-chemoradiotherapy group and 288 to the perioperative-chemotherapy group. A higher percentage of patients in the preoperative-chemoradiotherapy group than in the perioperative-chemotherapy group had a pathological complete response (17% vs. 8%) and greater tumor downstaging after resection. At a median follow-up of 67 months, no significant between-group differences in overall survival or progression-free survival were noted. The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death, 1.05; 95% confidence interval, 0.83 to 1.31), and the median progression-free survival was 31 months and 32 months, respectively. Treatment-related toxic effects were similar in the two groups.

CONCLUSIONS

The addition of preoperative chemoradiotherapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone among patients with resectable gastric and gastroesophageal junction adenocarcinoma. (Funded by the National Health and Medical Research Council and others; TOPGEAR ClinicalTrials.gov number, NCT01924819.)

Author Affiliations

From the Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre, University of Melbourne (T.L., M.M., W.K.M.), the School of Public Health, Monash University (J.Z.), the Department of Medical Oncology, Alfred Health (J.Z.), Central Clinical School, Alfred Centre (A.B.), and Monash Medical Centre (A.S.), Melbourne, VIC, Princess Alexandra Hospital, University of Queensland, Brisbane (B.M.S.), and Cancer Care Services, Sunshine Coast University Hospital, Birtinya, QLD (D.W.), National Health and Medical Research Council Clinical Trials Centre, University of Sydney (V.G., R.L.O., J.S.), and Chris O’Brien Lifehouse (D.M.), Sydney, and the Trans-Tasman Radiation Oncology Group, University of Newcastle, Newcastle, NSW (A.M.) — all in Australia; the Department of Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium (K.H.); Princess Margaret Hospital (R.W.) and Mount Sinai Hospital (C.S.), Toronto, the Canadian Cancer Trials Group, Queen’s University, Kingston, ON (C.O.), Nova Scotia Health Central Zone, Halifax (G.D.), and Centre Hospitalier de l’Université de Montréal, Montreal (M.L.) — all in Canada; the Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (M.F.); University Cancer Center Leipzig and Comprehensive Cancer Center Central Germany Leipzig–Jena, University Medicine Leipzig, Leipzig, Germany (F.L.); and Sainte Catherine Institut du Cancer Avignon–Provence, Avignon, France (L.M.).

Leave a Comment

Your email address will not be published. Required fields are marked *

Related Articles

Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer

The MATTERHORN trial assessed patients with resectable gastric cancer/gastroesophageal junction cancer and assigned them 1:1 to perioperative durvalumab 1500 mg Q4W + FLOT (neoadjuvant and adjuvant) vs placebo + FLOT. Durvalumab + FLOT significantly improved 2-yr EFS (67.4% vs 58.5%) and increased pathological complete response (pCR) (19.2% vs 7.2%), with a numerically higher 2-year overall survival (OS) (75.7% vs 70.4%). Safety was comparable between arms (grade 3–4 AEs 71.6% vs 71.2%) with no excess surgical delays, unexpected toxicities or adjuvant initiation delays. Bottom line: Immunotherapy (IO) benefit appears linked to the FLOT backbone—as cis/FP + IO regimens have not consistently improved event-free survival (EFS)—and mature OS plus broader representation remain needed, but this looks like a meaningful advance.

Read More »

Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer

The phase III DESTINY-Gastric04 trial randomized HER2+ metastatic gastric/GEJ adenocarcinoma progressing on trastuzumab to T-DXd versus RAM+PTX, showing a significant overall survival (OS) benefit with T-DXd (14.7 vs 11.4 months) and improved PFS (6.7 vs 5.6 months). Objective response rate (ORR) was higher with T-DXd (44.3% vs 29.1%), and duration of response was longer (7.4 vs 5.3 months). Grade ≥3 AE rates were comparable (50.0% vs 54.1%), though adjudicated ILD/pneumonitis was more frequent with T-DXd (13.9% vs 1.3%, mostly grade 1–2), underscoring the need for vigilant monitoring. Bottom line: T-DXd looks like the new second-line standard for HER2+ disease that stays HER2-positive post-trastuzumab—meaningful survival gains. Please make sure to plan for a repeat biopsy in this setting.

Read More »

Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer

The DESTINY-Gastric04 trial compared trastuzumab deruxtecan (T-DXd) vs ramucirumab + paclitaxel as second-line therapy for HER2+ advanced gastric or gastroesophageal junction (GEJ) cancer, showing significant improvements in progression-free survival (PFS) (7.1 vs 5.7 months) and overall survival (OS) (13.6 vs 10.2 months). The antibody-drug conjugate (ADC) also achieved a higher objective response rate (43.6% vs 28.4%). This is no surprise as this T-DXd seems to be a game changer in many diseases. Toxicities were as expected.

Read More »

Randomized Phase III Trial of Ramucirumab Beyond Progression Plus Irinotecan in Patients With Ramucirumab-Refractory Advanced Gastric Cancer: RINDBeRG Trial

The RINDBeRG phase III trial investigated Ram + IRI versus IRI alone in Ram-refractory advanced gastric cancer, showing a significant improvement in progression-free survival (PFS) (3.8 vs 2.8 months) but no significant difference in overall survival (OS) (9.4 vs 8.5 months). The combination therapy achieved a higher overall response rate (ORR) (22.1% vs 15.0%) and disease control rate (DCR) (64.4% vs 52.1%), indicating likely modest antitumor activity. This combo offers a slight edge in delaying progression, but the lack of overall survival (OS) benefit means we’ll need to carefully consider its role in practice.

Read More »
Load More