Initial Panitumumab Plus Fluorouracil, Leucovorin, and Oxaliplatin or Plus Fluorouracil and Leucovorin in Elderly Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer: The PANDA Trial by the GONO Foundation
Authors: Lonardi Sara , Rasola Cosimo , Lobefaro Riccardo , Rossini Daniele , Formica Vincenzo , Scartozzi Mario , Frassineti Giovanni Luca , Boscolo Giorgia , Cinieri Saverio , Di Donato Samantha , Pella Nicoletta , Bergamo Francesca , Raimondi Alessandra , Arnoldi Ermenegildo , Antonuzzo Lorenzo , Granetto Cristina , Zustovich Fable , Ronzoni Monica , Leo Silvana , Morano Federica , Loupakis Fotios , Buggin Federica , Zagonel Vittorina , Fassan Matteo , Cremolini Chiara , Boni Luca , Pietrantonio Filippo ,   on behalf of the GONO Foundation Investigators, Arnoldi Ermenegildo , Antonuzzo Lorenzo , Aprile Giuseppe , Ardizzoia Antonio , Aschele Carlo , Baldini Editta , Ballestrero Alberto , Bertolini Alessandro , Bordonaro Roberto , Boscolo Giorgia , Buonadonna Angela , Cinieri Saverio , Clavarezza Matteo , Corsi Domenico , Cortesi Enrico , De Braud Filippo , Di Donato Samantha , Falcone Alfredo , Favaretto Adolfo , Formica Vincenzo , Frassineti Luca , Frassoldati Antonio , Frisinghelli Michela , Gamucci Teresa , Gianni Luca , Giovanardi Filippo , Gori Stefania , Grande Roberta , Granetto Cristina , Leo Silvana , Leone Francesco , Lonardi Sara , Luciani Andrea , Milandri Carlo , Pella Nicoletta , Sartore-Bianchi Andrea , Scartozzi Mario , Silvestris Nicola , Tamburini Emiliano , Tomasello Gianluca , Tonini Giuseppe , Tortora Gianpaolo , Vergani Claudio , Zaniboni Albrto , Zustovich Fable 
Published: August 2023

PURPOSE

To verify whether both doublet chemotherapy with a modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) and monochemotherapy with fluorouracil plus leucovorin (5-FU + LV) achieve satisfactory efficacy when both regimens are combined with panitumumab (PAN) as initial treatment of elderly patients with RAS/ BRAF wild-type metastatic colorectal cancer (mCRC).

PATIENTS AND METHODS

PANDA (ClinicalTrials.gov identifier: NCT02904031 ) was an open-label, randomized phase II noncomparative trial in previously untreated patients age 70 years and older with unresectable RAS/ BRAF wild-type mCRC. Patients were randomly assigned 1:1 to mFOLFOX + PAN (arm A) or 5-FU + LV + PAN (arm B) for up to 12 cycles, followed by PAN maintenance. The primary end point was progression-free survival (PFS). In each arm, assuming a null hypothesis of median PFS time ≤6 months and target PFS ≥9.65, 90 patients per arm were needed to achieve 90% power and 5% type I error (one-sided Brookmeyer-Crowley test).

RESULTS

Between July 2016 and April 2019, 91 patients were randomly assigned to arm A and 92 to arm B. At a median follow-up of 50.0 months (IQR, 45.6-56.4), median PFS was 9.6 and 9.0 months for arm A and B, respectively ( P < .001 in each arm). Overall response rate was 69% and 52%, whereas median overall survival was 23.5 and 22.0 months in arm A and B, respectively. The overall rate of grade >2 chemotherapy-related adverse events was 60% and 37%, respectively. Baseline G8 and Chemotherapy Risk Assessment Scale for High-Age Patients scores were prognostic, but they were not associated with efficacy and safety of the two arms.

CONCLUSION

Both mFOLFOX and 5-FU + LV + PAN are reasonable options as initial therapy of elderly patients with RAS/ BRAF wild-type mCRC. 5-FU + LV + PAN is associated with a better safety profile.