ASPECCT: A Randomised, Multicentre, Open-Label, Phase 3 Study of Panitumumab Vs Cetuximab for Previously-Treated Wild-Type (WT) KRAS Metastatic Colorectal Cancer (mCRC) — ASN Events
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  3. ASPECCT: A Randomised, Multicentre, Open-Label, Phase 3 Study of Panitumumab Vs Cetuximab for Previously-Treated Wild-Type (WT) KRAS Metastatic Colorectal Cancer (mCRC)

ASPECCT: A Randomised, Multicentre, Open-Label, Phase 3 Study of Panitumumab Vs Cetuximab for Previously-Treated Wild-Type (WT) KRAS Metastatic Colorectal Cancer (mCRC) (#44)

Tim J Price 1 , Marc Peeters 2 , Tae W Kim 3 , Jin Li 4 , Stefano Cascinu 5 , Paul Ruff 6 , Atilli S Suresh 7 , Kathy Zhang 8 , Swaminathan Murugappan 8 , Roger Sidhu 8
  1. Queen Elizabeth Hospital, Woodville, SA, Australia
  2. Antwerp University Hospital and University of Antwerp, Antwerp, Belgium
  3. Asan Medical Center, University of Ulsan, Seoul, Korea
  4. Fudan University Cancer Hospital, Shanghai, China
  5. Universita Politecnica delle Marche, Ancona, Italy
  6. University of Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa
  7. Apollo Hospital, Hyderabad, India
  8. Amgen Inc., Thousand Oaks, USA

Background: Epidermal growth factor receptor (EGFR)-targeting monoclonal antibodies have demonstrated efficacy for the treatment of WT KRAS mCRC. ASPECCT is a non-inferiority trial comparing the efficacy and safety of panitumumab with cetuximab in chemorefractory WT KRAS mCRC.
Methods: Adult patients (ECOG PS 0-2, prior irinotecan, oxaliplatin and fluorouracil-based treatment for mCRC and no prior anti-EGFR treatment) were stratified by geographic region and ECOG PS and randomised 1:1 to receive panitumumab 6mg/kg q2w or cetuximab (400mg/m2 then 250mg/m2 qw) until disease progression (PD), intolerability, consent withdrawal or death. Treatment crossover was not allowed. The primary endpoint was overall survival (OS). Non-inferiority was concluded if panitumumab preserved at least 50% of the cetuximab OS effect versus best supportive care using a synthesis method. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. Global enrolment has been completed.
Results: 999 patients were randomised and treated: 499 panitumumab, 500 cetuximab. Demographics were balanced between arms. Non-inferiority of OS with panitumumab versus cetuximab was met. Median OS in the panitumumab and cetuximab arms was 10.4 and 10.0 months, respectively, hazard ratio (HR) (95% CI) (panitumumab:cetuximab): 0.97 (0.84–1.11); p=0.0007. OS retention rate (95% CI) was 1.06 (0.82–1.3). Median PFS was 4.1 and 4.4 months, respectively, HR (95% CI): 1.00 (0.88–1.14). ORRs were 22% and 19.8%, respectively. Worst grade 3, 4, and 5 adverse events (AEs) for panitumumab/cetuximab, respectively, were 36.3%/31.6%, 7.5%/5.4%, and 5.8%/9.9% (69% of all grade 5 AEs related to PD). Grade 3 and 4 (panitumumab/cetuximab, respectively) AEs of interest were skin toxicity 12.5%/9.5%, hypomagnesaemia 7.3%/2.6% and infusion reactions 0.2%/1.8%.
Conclusions: The phase 3 ASPECCT study met the primary endpoint of non-inferiority of OS of panitumumab versus cetuximab in chemorefractory WT KRAS mCRC. Observed safety profiles between the treatment arms were consistent with previously-reported studies for both agents.