World GI 2013 Press Release: Study Confirms Adding Chemotherapy to Surgery Improves Survival in Advanced Gastric Cancer

Lugano - Barcelona, 3 July 2013

For patients with advanced gastric cancer, treatment with chemotherapy after surgery can reduce the risk of cancer related death by 34% over five years compared to surgery alone, researchers said at the 15th ESMO World Congress in Gastrointestinal Cancer.

At the meeting Prof Sung Hoon Noh, a gastric surgeon from Yonsei University College of Medicine, Korea, presented 5-year follow-up from the phase III CLASSIC trial, which added combination chemotherapy to a standard surgical procedure called D2 gastrectomy. The chemotherapy regimen studied in the trial is called XELOX, which is a combination of the drugs capecitabine and oxaliplatin.

CLASSIC was a multinational open-label randomised phase III trial performed in South Korea, China and Taiwan. Patients with stage II–IIIB gastric cancer who had undergone curative D2 gastrectomy were assigned to adjuvant XELOX for eight cycles or surgery alone. The primary endpoint was 3-year disease-free survival.

The clinical cut-off date for the prospectively planned final 5-year efficacy analysis was in November 2012. At that point, 103 (20%) patients in the XELOX group and 141 (27%) patients in the surgery alone group had died. This represented a 34% reduction in the risk of death with XELOX versus surgery alone, which is higher than the 28% reduction previously reported after three years of follow-up.

“Surgery is the most important modality in gastric cancer treatment and in the past it was considered that gastric cancer could be cured by surgery alone, if the surgery was properly performed,” Dr Noh said. “However, there has been controversy over whether surgery is enough in advanced disease. The new CLASSIC data clearly shows that a XELOX regimen administered after surgery prolongs the lives of patients with gastric cancer compared to patients who had surgery alone.”

The further benefits in cancer mortality risk compared to the earlier analysis are statistically significant and clinically highly relevant, Prof Noh said. “There is no doubt that XELOX is an effective therapy in the adjuvant setting.”

The study also shows the importance of treatment with a multidisciplinary team of oncologists, Prof Noh said. “This work was done by collaboration between surgeons and medical oncologists. To win the war on cancer, collaboration is one of most important virtues across disciplines.”

Commenting on the study, ESMO spokesperson Andrés Cervantes, Professor of Medicine at the University of Valencia, Spain, said the new findings were very important because they report mature survival data.

“Many trials reporting the effect of postoperative chemotherapy after gastrectomy for gastric cancer patients have failed in finding a significant benefit in survival,” notes Dr Cervantes, who was not involved in the study. “This is a well designed trial.”

Although a meta-analysis published in recent years showed that chemotherapy after a surgical resection of gastric cancer improved survival, most single studies have been negative, Dr Cervantes noted. “Having a positive study in this setting with drugs that are available in any country in Europe or even worldwide is definitely important.”

Notes to Editors

References

1. Abstracts from the 15th ESMO World Congress on Gastrointestinal Cancer are published in Annals of Oncology, Volume 24 suppls 4 June 2013 (Ann Oncol 2013 Jun; 24(Suppl 4): 5-130) http://annonc.oxfordjournals.org/content/24/suppl_4.toc 
2. Abstract presentation: Thursday, 4 July 2013, 17:25 hrs, Session VII: Gastric Cancer

About the ESMO World Congress on Gastrointestinal Cancer

The ESMO World Congress on Gastrointestinal Cancer is the premier global event in the field, encompassing malignancies affecting every component of the gastrointestinal tract and aspects related to the care of patients with gastrointestinal cancer, including screening, diagnosis and the latest management options for common and uncommon tumours. It has been endorsed by leading professional societies and organizations.
The ESMO 15th World Congress on Gastrointestinal Cancer has been organized in partnership with ESMO (European Society for Medical Oncology). The Congress is developed and managed by Imedex®, LLC.

About the European Society for Medical Oncology

The European Society for Medical Oncology (ESMO) is the leading European professional organization committed to advancing the specialty of medical oncology and promoting a multidisciplinary approach to cancer treatment and care.
ESMO’s mission is to advance cancer care and cure through fostering and disseminating good science that leads to better medicine and determines best practice.
ESMO’s scientific journal, Annals of Oncology, ranks among the top clinical oncology journals worldwide. ESMO events are the meeting place in Europe for medical oncologists to update their knowledge, to network and to exchange ideas.
To find out more about ESMO, please visit: www.esmo.org 

ABSTRACT 0007

Adjuvant capecitabine and oxaliplatin (XELOX) for gastric cancer after D2 gastrectomy: final results from the CLASSIC trial

Sung Hoon Noh 1, Sook Ryun Park 2, Han-Kwang Yang 3, Hyun Cheol Chung 1, Ik-Joo Chung 4, Kyung Hee Lee 5, Hyung-Ho Kim 6, Jiafu Ji 7, Jen-Shi Chen 8, Yunni Lim 9, Stella Ha 9, Yung-Jue Bang 3

1 Yonsei University College of Medicine, Seodeamungyu Shinchon-dong 134, Seoul, 2 Research Institute and Hospital, National Cancer Center, Ilsandong-gu, Goyang-si Gyeonggi-do, 3 Seoul National University College of Medicine, Jongno-gu, Seoul, 4 Chonnam National University Hwasun Hospital, Hwasun-Eup, Hwasun-Gun, Jeonnam, 5 Yeungnam University College of Medicine, Nam-gu, Daegu, 6 Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, 7 Beijing Cancer Hospital, Haidian, Beijing, 8 Chang Gung Memorial Hospital, Kwei-Shan Shiang, Taoyuan, 9 Roche Korea Co.,Ltd, Seocho-Gu, Seoul

Background: D2 gastrectomy, which is widely used in East Asia as the preferred surgery for patients with operable gastric cancer, is now recommended in US and European treatment guidelines for gastric cancer. Two phase III trials (ACTS-GC and CLASSIC) have been performed to assess the possible benefits of adjuvant chemotherapy after D2 surgery. ACTS-GC showed a survival benefit with fluoropyrimidine monotherapy after D2 gastrectomy compared with surgery only [Sasako et al. J Clin Oncol 2011;29:4387–93]. The CLASSIC trial compared fluoropyrimidine-oxaliplatin combination therapy (XELOX) with surgery alone; interim results showed that XELOX improved 3-year disease-free survival after D2 gastrectomy compared with surgery only [Bang et al. Lancet 2012;379:315–21]. Improved overall survival was also evident after only 3 years, but the data were immature. We report here the final results from the CLASSIC trial after a median follow-up of 5 years.

Methods: CLASSIC was a multinational open-label randomised phase III trial performed in South Korea, China, and Taiwan. Randomisation was stratified by country and disease stage. Patients with stage II–IIIB gastric cancer who had undergone curative D2 gastrectomy were assigned to adjuvant XELOX (oxaliplatin 130 mg/m2 day 1 plus capecitabine 1000 mg/m2 twice daily days 1–14 q3w) for 8 cycles or surgery alone. The primary endpoint was 3-year disease-free survival. The clinical cut-off date for the prospectively planned final 5-year efficacy analysis was 22 November 2012.

Results: At data cut-off, 103 (20%) patients in the XELOX group and 141 (27%) patients in the surgery alone group had died. This represented a 34% reduction in the risk of death with XELOX versus surgery alone (hazard ratio 0.66, 95% CI 0.51–0.85; p=0.0015 by stratified Cox regression analysis). The 5-year overall survival rate was 78% in the XELOX group and 69% in the surgery alone group (p=0.0029, log-rank test unstratified). 76 (15%) patients in the XELOX group and 135 (26%) patients in the surgery alone group received subsequent, non-protocol-specified anticancer therapies after progression of disease. In the analysis of disease-free survival, 139 (26.7%) patients in the XELOX group and 203 (39.4%) patients in the surgery alone group had relapsed, developed a new gastric cancer or died. This represented a 42% reduction in the risk of an event with XELOX versus surgery alone (hazard ratio 0.58, 95% CI 0.47–0.72; p<0.0001 by stratified Cox regression analysis). The 5-year disease-free survival rate was 68% in the XELOX group and 53% in the surgery alone group (p<0.0001, log-rank test unstratified).

Conclusion:

The final analysis of the CLASSIC trial, after a median follow-up of 5 years, supports the findings from the primary analysis performed 2 years earlier. Adjuvant XELOX after curative D2 gastrectomy improves overall survival compared with surgery alone and should be considered as a standard treatment option for patients with operable gastric cancer.