Ann-Lii Cheng1, Gerardo Cornelio2, Lin Shen3, Timothy Price4, Tsai-Sheng Yang5, Ik Joo Chung6, Guang-Hai Dai7, Jen-Kou Lin8, Atul Sharma9, Kun-Huei Yeh10, Brigette Ma11, Adel Zaatar12, Zhongzhen Guan13, Nehal Masood14, Vichien Srimuninnimit15, Thomas Yau16, Peter Gibbs17, Xiuwen Wang18, Dinesh Chandra Doval19, Seung-Taek Oh20, Byoung Yong Shim21, Charity Gorospe22, Hwei-Ming Wang23, Ekaphop Sirachainan15, Andrew Hill24, Kwang Wook Suh25, Frank Beier26, Sudipto Chatterjee27, Robert Lim28. 1. National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan. Electronic address: alcheng@ntu.edu.tw. 2. San Juan de Dios Hospital, Pasay City, Philippines. 3. Peking University Cancer Hospital and Institute, Beijing, China. 4. Queen Elizabeth Hospital, Woodville, Australia. 5. Chang Gung Memorial Hospital-LinKou, Taoyuan, Taiwan. 6. Chonnam National University Hwasun Hospital, Hwasun-eup, South Korea. 7. The General Hospital of the People's Liberation Army, Beijing, China. 8. Taipei Veterans General Hospital, Taipei, Taiwan. 9. All India Institute of Medical Sciences, New Delhi, India. 10. National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan. 11. Chinese University of Hong Kong, Prince of Wales Hospital, Sha Tin, New Territories, Hong Kong, China. 12. Mount Miriam Cancer Hospital, Penang, Malaysia. 13. Sun Yat-sen University Cancer Center, Guangzhou, China. 14. The Aga Khan University and Hospital, Karachi, Pakistan. 15. Ramathibodi Hospital, Siriraj Hospital, Bangkok, Thailand. 16. Queen Mary Hospital, Pok Fu Lam, Hong Kong. 17. Western Hospital, Australia. 18. Qilu Hospital of Shandong University, Shandong, China. 19. Rajiv Gandhi Cancer Institute & Research Centre, Rohini, New Delhi, India. 20. The Catholic University of Korea: Seoul St. Mary's Hospital, Seoul, Republic of Korea. 21. The Catholic University of Korea: St. Vincent's Hospital, Paldal-Gu, Suwon, Republic of Korea. 22. St Luke's Medical Center, Philippines. 23. Taichung Veterans General Hospital, Taichung City, Taiwan. 24. Gold Coast Hospital, Southport, Queensland, Australia. 25. Ajou University Hospital, Yeongtong-gu, Suwon, Republic of Korea. 26. Merck KGaA, Darmstadt, Germany. 27. Merck Ltd, Mumbai, India. 28. National University Cancer Institute, Singapore.
Abstract
BACKGROUND: In patients with KRAS wild-type (wt) metastatic colorectal cancer (mCRC), outcomes with first-line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first-line once-every-2-weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed. PATIENTS AND METHODS: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region. Patients (n = 289) received once-every-2-weeks cetuximab with investigator's choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression-free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated. RESULTS: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations. CONCLUSION: The observed activity and safety profile is similar to that reported in prior first-line pivotal studies involving weekly cetuximab, suggesting once-every-2-weeks cetuximab is effective and tolerable as first-line therapy and may represent an alternative to weekly administration.
BACKGROUND: In patients with KRAS wild-type (wt) metastatic colorectal cancer (mCRC), outcomes with first-line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first-line once-every-2-weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed. PATIENTS AND METHODS: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region. Patients (n = 289) received once-every-2-weeks cetuximab with investigator's choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression-free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated. RESULTS: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations. CONCLUSION: The observed activity and safety profile is similar to that reported in prior first-line pivotal studies involving weekly cetuximab, suggesting once-every-2-weeks cetuximab is effective and tolerable as first-line therapy and may represent an alternative to weekly administration.