Clinical Trial

. 2018 Jan 25;18(1):98.

doi: 10.1186/s12885-018-4001-x.

The PANDA study: a randomized phase II study of first-line FOLFOX plus panitumumab versus 5FU plus panitumumab in RAS and BRAF wild-type elderly metastatic colorectal cancer patients

Francesca Battaglin¹, Marta Schirripa¹, Federica Buggin¹, Filippo Pietrantonio², Federica Morano², Giorgia Boscolo³, Giuseppe Tonini⁴, Eufemia Stefania Lutrino⁵, Jessica Lucchetti⁶, Lisa Salvatore⁷, Alessandro Passardi⁸, Chiara Cremolini⁹, Ermenegildo Arnoldi¹⁰, Mario Scartozzi¹¹, Nicoletta Pella¹², Luca Boni¹³, Francesca Bergamo¹, Vittorina Zagonel¹, Fotios Loupakis¹⁴, Sara Lonardi¹⁵

Affiliations

¹ Istituto Oncologico Veneto - IRCCS, S.C. Oncologia Medica 1, Dipartimento di Oncologia Clinica e Sperimentale, Via Gattamelata, 64, 35128, Padova, Italy.
² Fondazione IRCCS Istituto Nazionale Tumori, Dipartimento di Oncologia Medica, Via Venezian, 1, 20133, Milan, Italy.
³ Azienda Unita Locale Socio-Sanitaria N°3 Serenissima - Distretto Mirano, Dolo, Noale - Dipartimento di Scienze Mediche, U.O.C. Oncologia ed Ematologia Oncologica, Via Don G. Sartor, 4, 30035, Mirano, VE, Italy.
⁴ Policlinico Universitario Campus Bio-Medico, U.O.C. Oncologia Medica, Via Alvaro del Portillo, 200, 00128, Rome, Italy.
⁵ Ospedale Senatore A. Perrino, U.O.C. Oncologia Medica, Strada Statale 7 (Appia), 72100, Brindisi, Italy.
⁶ U.O. Oncologia Medica, Dipartimento di Medicina, Ospedale Universitario Policlinico Tor Vergata, Università degli Studi di Roma Tor Vergata, Viale Oxford, 81, 00133, Rome, Italy.
⁷ Oncologia, Azienda Ospedaliera Universitaria Integrata di Verona, Piazzale Scuro, 10, 37134, Verona, Italy.
⁸ IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), U.O. Oncologia Medica, Via P. Maroncelli, 40, 47014, Meldola, FC, Italy.
⁹ Azienda Ospedaliero Universitaria Pisana, U.O. Oncologia Medica 2 Universitaria, Via Roma, 67, 56126, Pisa, Italy.
¹⁰ ASST Papa Giovanni XXIII, U.O. Oncologia Medica, Piazza OMS, 1, 24127, Bergamo, Italy.
¹¹ U.O. Oncologia Medica, Azienda Ospedaliero-Universitaria di Cagliari e Università di Cagliari, via Ospedale, 54, 09124, Cagliari, Italy.
¹² Azienda Sanitaria Universitaria Integrata di Udine, Dipartimento di Oncologia, Piazzale Santa Maria della Misericordia, 15, 33100, Udine, Italy.
¹³ Centro Coordinamento Sperimentazioni Cliniche - Istituto Toscano Tumori, Via Taddeo Alderotti, 26/N, 50139, Florence, Italy.
¹⁴ Istituto Oncologico Veneto - IRCCS, S.C. Oncologia Medica 1, Dipartimento di Oncologia Clinica e Sperimentale, Via Gattamelata, 64, 35128, Padova, Italy. fotios.loupakis@iov.veneto.it.
¹⁵ Istituto Oncologico Veneto - IRCCS, S.C. Oncologia Medica 1, Dipartimento di Oncologia Clinica e Sperimentale, Via Gattamelata, 64, 35128, Padova, Italy. sara.lonardi@iov.veneto.it.

PMID: 29370781
PMCID: PMC5784655
DOI: 10.1186/s12885-018-4001-x

Clinical Trial

The PANDA study: a randomized phase II study of first-line FOLFOX plus panitumumab versus 5FU plus panitumumab in RAS and BRAF wild-type elderly metastatic colorectal cancer patients

Francesca Battaglin et al. BMC Cancer. 2018.

. 2018 Jan 25;18(1):98.

doi: 10.1186/s12885-018-4001-x.

Authors

Affiliations

¹ Istituto Oncologico Veneto - IRCCS, S.C. Oncologia Medica 1, Dipartimento di Oncologia Clinica e Sperimentale, Via Gattamelata, 64, 35128, Padova, Italy.
² Fondazione IRCCS Istituto Nazionale Tumori, Dipartimento di Oncologia Medica, Via Venezian, 1, 20133, Milan, Italy.
³ Azienda Unita Locale Socio-Sanitaria N°3 Serenissima - Distretto Mirano, Dolo, Noale - Dipartimento di Scienze Mediche, U.O.C. Oncologia ed Ematologia Oncologica, Via Don G. Sartor, 4, 30035, Mirano, VE, Italy.
⁴ Policlinico Universitario Campus Bio-Medico, U.O.C. Oncologia Medica, Via Alvaro del Portillo, 200, 00128, Rome, Italy.
⁵ Ospedale Senatore A. Perrino, U.O.C. Oncologia Medica, Strada Statale 7 (Appia), 72100, Brindisi, Italy.
⁶ U.O. Oncologia Medica, Dipartimento di Medicina, Ospedale Universitario Policlinico Tor Vergata, Università degli Studi di Roma Tor Vergata, Viale Oxford, 81, 00133, Rome, Italy.
⁷ Oncologia, Azienda Ospedaliera Universitaria Integrata di Verona, Piazzale Scuro, 10, 37134, Verona, Italy.
⁸ IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), U.O. Oncologia Medica, Via P. Maroncelli, 40, 47014, Meldola, FC, Italy.
⁹ Azienda Ospedaliero Universitaria Pisana, U.O. Oncologia Medica 2 Universitaria, Via Roma, 67, 56126, Pisa, Italy.
¹⁰ ASST Papa Giovanni XXIII, U.O. Oncologia Medica, Piazza OMS, 1, 24127, Bergamo, Italy.
¹¹ U.O. Oncologia Medica, Azienda Ospedaliero-Universitaria di Cagliari e Università di Cagliari, via Ospedale, 54, 09124, Cagliari, Italy.
¹² Azienda Sanitaria Universitaria Integrata di Udine, Dipartimento di Oncologia, Piazzale Santa Maria della Misericordia, 15, 33100, Udine, Italy.
¹³ Centro Coordinamento Sperimentazioni Cliniche - Istituto Toscano Tumori, Via Taddeo Alderotti, 26/N, 50139, Florence, Italy.
¹⁴ Istituto Oncologico Veneto - IRCCS, S.C. Oncologia Medica 1, Dipartimento di Oncologia Clinica e Sperimentale, Via Gattamelata, 64, 35128, Padova, Italy. fotios.loupakis@iov.veneto.it.
¹⁵ Istituto Oncologico Veneto - IRCCS, S.C. Oncologia Medica 1, Dipartimento di Oncologia Clinica e Sperimentale, Via Gattamelata, 64, 35128, Padova, Italy. sara.lonardi@iov.veneto.it.

PMID: 29370781
PMCID: PMC5784655
DOI: 10.1186/s12885-018-4001-x

Abstract

Background: Few data are available regarding the treatment of metastatic colorectal cancer elderly patients with anti-EGFR agents in combination with chemotherapy. FOLFOX plus panitumumab is a standard first-line option for RAS wild-type metastatic colorectal cancer. Slight adjustments in chemo-dosage are commonly applied in clinical practice to elderly patients, but those modified schedules have never been prospectively tested. Clinical definition of elderly (≥70 years old) patients that may deserve a more or less intensive combination therapy is still debated. Several geriatric screening tools have been developed to predict survival and risk of toxicity from treatment. Among those, the G8 screening tool has been tested in cancer patients showing the strongest prognostic value for overall survival, while the CRASH score can stratify patients according to an estimated risk of treatment-related toxicities.

Methods: The PANDA study is a prospective, open-label, multicenter, randomized phase II trial of first-line therapy with panitumumab in combination with dose-adjusted FOLFOX or with 5-fluorouracil monotherapy, in previously untreated elderly patients (≥70 years) with RAS and BRAF wild-type unresectable metastatic colorectal cancer. RAS and BRAF analyses are centralized. Geriatric assessment by means of G8 and CRASH score is planned at baseline and G8 will be re-evaluated at disease progression. The primary endpoint is duration of progression-free survival in both arms. Secondary endpoints include prospective evaluation of the prognostic role of G8 score and the correlation of CRASH risk categories with toxicity.

Discussion: The PANDA study aims at exploring safety and efficacy of panitumumab in combination with FOLFOX or with 5FU/LV in elderly patients affected by RAS and BRAF wild-type metastatic colorectal cancer, to identify the most promising treatment strategy in this setting. Additionally, this is the first trial in which the prognostic role of the G8 score will be prospectively evaluated. Results of this study will drive further experimental developments for one or both combinations.

Trial registration: PANDA is registered at Clinicaltrials.gov : NCT02904031 , July 11, 2016. PANDA is registered at EudraCT-No.: 2015-003888-10, September 3, 2015.

Keywords: BRAF; CRASH; Clinical trial; Elderly; G8; Metastatic colorectal cancer; Panitumumab; RAS.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The trial was approved by the Ethics Committee of the Istituto Oncologico Veneto IRCCS and by local Committees of participating centers. All study participants will provide their written informed consent after careful explanation by their treating investigators.

Consent for publication

Not applicable

Competing interests

Fotios Loupakis is an advisor/speaker for Amgen Inc., Bayer Healthcare, Eli Lilly and Company and Roche. Sara Lonardi is an advisor/speaker for Amgen Inc., Bayer Healthcare, Eli Lilly and Company, Roche and Sanofi. Filippo Pietrantonio has advisory role/honoraria for Amgen Inc., Roche, Sanofi, Eli Lilly and Company and Bayer Healthcare. Mario Scartozzi is an advisor/speaker for Merck-Serono, Bristol-Myers Squibb, Amgen Inc., Bayer Healthcare, Eli Lilly and Company and Sanofi-Aventis.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Study Design. *Pan = panitumumab

See this image and copyright information in PMC

References

1. Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67(3):177–193. doi: 10.3322/caac.21395. - DOI - PubMed
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1. Sorbye H, Pfeiffer P, Cavalli-Bjorkman N, et al. Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients. Cancer. 2009;115:4679–4687. doi: 10.1002/cncr.24527. - DOI - PubMed
1. Papamichael D, Audisio RA, Glimelius B, et al. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol. 2015;26:463–476. doi: 10.1093/annonc/mdu253. - DOI - PubMed
1. Cunningham D, Lang I, Marcuello E, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14:1077–1085. doi: 10.1016/S1470-2045(13)70154-2. - DOI - PubMed

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The PANDA study: a randomized phase II study of first-line FOLFOX plus panitumumab versus 5FU plus panitumumab in RAS and BRAF wild-type elderly metastatic colorectal cancer patients

Affiliations

The PANDA study: a randomized phase II study of first-line FOLFOX plus panitumumab versus 5FU plus panitumumab in RAS and BRAF wild-type elderly metastatic colorectal cancer patients

Authors

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

Publication types

MeSH terms

Substances

Supplementary concepts

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous