Impact of early tumor shrinkage and depth of response on the outcomes of panitumumab-based maintenance in patients with RAS wild-type metastatic colorectal cancer

被引：16

作者：

Manca, Paolo ^{[1
]}

Corallo, Salvatore ^{[1
]}

Randon, Giovanni ^{[1
]}

Lonardi, Sara ^{[2
]}

Cremolini, Chiara ^{[3
]}

Rimassa, Lorenza ^{[4
,5
]}

Bergamo, Francesca ^{[2
]}

Antoniotti, Carlotta ^{[3
]}

Smiroldo, Valeria ^{[4
]}

Zaniboni, Alberto ^{[6
]}

Murialdo, Roberto ^{[7
,8
]}

Tampellini, Marco ^{[9
]}

Tomasello, Gianluca ^{[10
]}

Clavarezza, Matteo ^{[11
]}

Racca, Patrizia ^{[12
]}

Antista, Maria ^{[1
]}

Raimondi, Alessandra ^{[1
]}

Prisciandaro, Michele ^{[1
]}

Pagani, Filippo ^{[1
]}

Palermo, Federica ^{[1
]}

Greco, Francesca Gabriella ^{[13
]}

Vaiani, Marta ^{[13
]}

Di Bartolomeo, Maria ^{[1
]}

de Braud, Filippo ^{[1
,14
]}

Calareso, Giuseppina ^{[13
]}

Morano, Federica ^{[1
]}

Pietrantonio, Filippo ^{[1
,14
]}

机构：

[1] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy

[2] Ist Oncol Veneto, Dept Clin & Expt Oncol, Unit Med Oncol 1, Padua, Italy

[3] Univ Pisa, Med Oncol Unit, Azienda Osped Univ Pisana, Dept Translat Res & New Technol Med, Pisa, Italy

[4] IRCCS, Humanitas Clin & Res Ctr, Humanitas Canc Ctr, Med Oncol & Hematol Unit, Rozzano, Italy

[5] Humanitas Univ, Dept Biomed Sci, Pieve Emanuele, Italy

[6] Fdn Poliambulanza, Med Oncol Unit, Brescia, Italy

[7] Univ Genoa, Dept Internal Med Di MI, Genoa, Italy

[8] IRCCS AOU San Martino IST, Genoa, Italy

[9] Univ Turin, AOU San Luigi Orbassano, Dept Oncol, Turin, Italy

[10] ASST Osped Cremona, Med Oncol Unit, Cremona, Italy

[11] Ente Osped Osped Galliera, Med Oncol Unit, Genoa, Italy

[12] AOU Citta Salute & Sci Torino, Dipartimento Oncol, SSD ColoRectal Canc Unit, Turin, Italy

[13] Fdn IRCCS Ist Nazl Tumori, Dept Radiol, Milan, Italy

[14] Univ Milan, Oncol & Hematooncol Dept, Milan, Italy

来源：

EUROPEAN JOURNAL OF CANCER | 2021年 / 144卷

关键词：

Metastatic colorectal cancer; Early tumor shrinkage; Depth of response; Maintenance therapy; Panitumumab; RAS wild-type; Molecular hyper-selection; EGFR MONOCLONAL-ANTIBODIES; PLUS BEVACIZUMAB; RESISTANCE; CETUXIMAB; FIRE-3; TRIAL;

D O I：

10.1016/j.ejca.2020.11.017

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: In patients with metastatic colorectal cancer (mCRC) receiving highly active first-line combination treatments, early tumor shrinkage (ETS) and depth of response (DoR) are associated with survival, but their influence on outcomes during maintenance therapy is unknown. The Valentino study showed inferior PFS in 229 RAS wild-type mCRC patients randomized to panitumumab plus FOLFOX followed by maintenance with panitumumab vs. panitumumab + 5-FU/LV. Patients and methods: After blinded independent central review of ETS (>= 20% reduction of the sum of target lesions) and DoR in patients enrolled in Valentino, the prognostic and predictive role of such parameters was investigated, along with their combination with PRESSING panel (uncommon genomic alterations associated with anti-EGFRs resistance beyond RAS and BRAF). Results: One hundred and ninety-six patients were included (ETS in 132 [67.3%], median DoR: 44.1%). Both ETS and DoR >= 34% were associated with longer mPFS (p = 0.010 and p < 0.001) and mOS (p = 0.006 and p < 0.001). The PFS benefit of 5-FU/LV added to panitumumab maintenance, reported in the study, was independent from ETS and DoR status (interaction tests NS for both PFS and OS). However, outcomes were extremely poor in patients who received single-agent panitumumab and had no-ETS (mPFS and mOS: 7.7 and 18.7 months) or DoR < 34% (mPFS and mOS: 6.5 and 18 months). Combining PRESSING panel ('molecular hyperselection') and response dynamics allowed to stratify both PFS (p < 0.001 and p < 0.001 for ETS and DoR, respectively) and OS (p < 0.001 and p = 0.017 for ETS and DoR, respectively). Conclusions: ETS and DoR allow on-treatment anticipation of outcomes following an anti-EGFR-based strategy planning de-escalation, and poor radiological response may guide enrolment in crossover strategy trials. As in vivo markers of drug sensitivity, ETS and DoR may be integrated with several patient- and tumor-related factors to wisely drive decision-making on upfront treatment duration and intensity. (C) 2020 The Author(s). Published by Elsevier Ltd.

引用

页码：31 / 40

页数：10

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