Single-Agent Panitumumab in Frail Elderly Patients With Advanced RAS and BRAF Wild-Type Colorectal Cancer: Challenging Drug Label to Light Up New Hope.
BACKGROUND
No prospective trials have specifically addressed the efficacy and safety of panitumumab in elderly patients with metastatic colorectal cancer (CRC). We aimed at assessing the efficacy and safety of single agent panitumumab in "frail" elderly patients diagnosed with metastatic RAS and BRAF wild-type CRC.


MATERIALS AND METHODS
Forty elderly patients (aged ≥ 75 years) with metastatic RAS-BRAF wild-type CRC received off-label prescriptions of single-agent panitumumab at seven Italian institutions. Treatment was administered as first line in patients with absolute contraindication to any chemotherapy or as second-line treatment after failure of a fluoropyrimidine-based treatment, in the presence of contraindication to irinotecan. The outcome measures included objective response rate (ORR), as well as progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety.


RESULTS
The median PFS and OS were 6.4 months (95% confidence interval [CI]: 4.9-8 months) and 14.3 months (95% CI: 10.9-17.7 months), respectively. ORR was 32.5%, and DCR was 72.5%. Dose reductions related to adverse events (AEs) were reported in 9 (23%) patients, but no permanent treatment discontinuation caused by was reported. The most frequent grade 3 AE was skin rash, with an incidence of 20%.


CONCLUSION
Panitumumab is effective and well-tolerated in frail elderly patients with RAS-BRAF wild-type metastatic CRC and deemed unfit for chemotherapy. A randomized study is needed to confirm these data.


IMPLICATIONS FOR PRACTICE
Treatment of elderly patients with metastatic colorectal cancer represents a difficult challenge in clinical practice. A significant proportion of frail elderly patients do not receive treatment, reflecting ongoing uncertainty of clinical benefit and toxicity of chemotherapy. Unfit condition in this cohort of patients further limits antineoplastic prescription and consequently patient survival. RAS and BRAF wild-type status could help select an elderly and unfit population that could benefit from anti-epidermal growth factor receptor single agent therapy. In the present study, single-agent off-label panitumumab was effective and well-tolerated as first-line treatment in frail elderly patients deemed unfit for chemotherapy for metastatic RAS and BRAF wild-type colorectal cancer.
['Pietrantonio|Filippo|F|', 'Cremolini|Chiara|C|', 'Aprile|Giuseppe|G|', 'Lonardi|Sara|S|', 'Orlandi|Armando|A|', 'Mennitto|Alessia|A|', 'Berenato|Rosa|R|', 'Antoniotti|Carlotta|C|', 'Casagrande|Mariaelena|M|', 'Marsico|Valentina|V|', 'Marmorino|Federica|F|', 'Cardellino|Giovanni Gerardo|GG|', 'Bergamo|Francesca|F|', 'Tomasello|Gianluca|G|', 'Formica|Vincenzo|V|', 'Longarini|Raffaella|R|', 'Giommoni|Elisa|E|', 'Caporale|Marta|M|', 'Di Bartolomeo|Maria|M|', 'Loupakis|Fotios|F|', 'de Braud|Filippo|F|']
D000368:Aged D000369:Aged, 80 and over D000911:Antibodies, Monoclonal D015179:Colorectal Neoplasms D018572:Disease-Free Survival D004348:Drug Labeling D066246:ErbB Receptors D005260:Female D016330:Frail Elderly D006801:Humans D053208:Kaplan-Meier Estimate D008297:Male D009362:Neoplasm Metastasis D000077544:Panitumumab D048493:Proto-Oncogene Proteins B-raf D018631:ras Proteins
Panitumumab Frail Elderly Metastatic colorectal cancer