TremelImumab and Durvalumab Combination for the Non-OperatIve Management (NOM) of Microsatellite InstabiliTY (MSI)-High Resectable Gastric or Gastroesophageal Junction Cancer: The Multicentre, Single-Arm, Multi-Cohort, Phase II INFINITY Study

被引：47

作者：

Raimondi, Alessandra ^{[1
]}

Palermo, Federica ^{[1
]}

Prisciandaro, Michele ^{[1
]}

Aglietta, Massimo ^{[2
]}

Antonuzzo, Lorenzo ^{[3
,4
]}

Aprile, Giuseppe ^{[5
]}

Berardi, Rossana ^{[6
]}

Cardellino, Giovanni G. ^{[7
]}

De Manzoni, Giovanni ^{[8
]}

De Vita, Ferdinando ^{[9
]}

Di Maio, Massimo ^{[10
]}

Fornaro, Lorenzo ^{[11
]}

Frassineti, Giovanni L. ^{[12
]}

Granetto, Cristina ^{[13
]}

Iachetta, Francesco ^{[14
]}

Lonardi, Sara ^{[15
]}

Murialdo, Roberto ^{[16
]}

Ongaro, Elena ^{[17
]}

Pucci, Francesca ^{[18
]}

Ratti, Margherita ^{[19
]}

Silvestris, Nicola ^{[20
,21
]}

Smiroldo, Valeria ^{[22
]}

Spallanzani, Andrea ^{[23
]}

Strippoli, Antonia ^{[24
]}

Tamberi, Stefano ^{[25
]}

Tamburini, Emiliano ^{[26
]}

Zaniboni, Alberto ^{[27
]}

Di Bartolomeo, Maria ^{[1
]}

Cremolini, Chiara ^{[28
]}

Sposito, Carlo ^{[29
]}

Mazzaferro, Vincenzo ^{[29
]}

Pietrantonio, Filippo ^{[1
]}

机构：

[1] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, I-20133 Milan, Italy

[2] IRCCS, Candiolo Canc Inst, Med Oncol Unit, FPO, I-10060 Candiolo, Italy

[3] Careggi Univ Hosp, Clin Oncol Unit, I-50139 Florence, Italy

[4] Univ Florence, Dept Expt & Clin Med, I-50121 Florence, Italy

[5] Osped Vicenza, Dept Clin Oncol, Azienda ULSS 8 Berica, I-36100 Vinceza, Italy

[6] Univ Politecn Marche, Dept Clin Oncol, AOU Osped Riuniti Ancona, I-60126 Ancona, Italy

[7] Presidio Osped Santa Maria Misericordia, Dept Oncol, ASUFC, I-33100 Udine, Italy

[8] Azienda Osped Univ Integrata Verona Borgo Trento, Dept Surg, I-37126 Verona, Italy

[9] Univ Campania Luigi Vanvitelli, Med Oncol Unit, Azienda Osped Univ, I-80131 Naples, Italy

[10] Osped Mauriziano Umberto 1, Dept Oncol, I-10128 Turin, Italy

[11] Azienda Osped Univ Pisana, Med Oncol 2, I-56126 Pisa, Italy

[12] IRCCS, Ist Romagnolo Studio Tumori Dino Amadori IRST, Dept Med Oncol, I-47014 Meldola, Italy

[13] Azienda Ospedaliera S Croce & Carle, Med Oncol, I-12100 Cuneo, Italy

[14] IRCCS Reggio Emilia, Dept Med Oncol, Azienda Unita Sanitaria Locale, I-42122 Reggio Emilia, Italy

[15] IRCCS Ist Oncol Veneto, Dept Clin & Expt Oncol, I-35128 Padua, Italy

[16] Osped Policlin San Martino, Med Oncol, I-16132 Genoa, Italy

[17] IRCCS, Ctr Riferimento Oncol Aviano CRO, Dept Med Oncol, I-33081 Aviano, Italy

[18] Azienda Osped Univ Parma, Med Oncol Unit, I-43126 Parma, Italy

[19] Azienda Sociosanitaria Terr Cremona, Oncol Dept, I-26100 Cremona, Italy

[20] Tabriz Univ Med Sci, Fac Adv Med Sci, Dept Mol Med, Tabriz 15731, Iran

[21] IRCCS Ist Tumori Giovanni Paolo II Bari, Med Oncol Unit, I-70124 Bari, Italy

[22] Humanitas Clin & Res Ctr, Humanitas Canc Ctr, I-20089 Milan, Italy

[23] Azienda Osped Univ Modena, Med Oncol Unit, I-41125 Modena, Italy

[24] Policlin Univ A Gemelli, Med Oncol Unit, I-00168 Rome, Italy

[25] Azienda USL Romagna, Med Oncol, I-48018 Faenza, Italy

[26] Azienda Osped Cardinale G Panico, Med Oncol Unit, I-73039 Tricase, Italy

[27] Fdn Poliambulanza, Dept Med Oncol, I-25124 Brescia, Italy

[28] Univ Pisa, Dept Translat Res & New Technol Med & Surg, I-56126 Pisa, Italy

[29] Fdn IRCCS Ist Nazl Tumori, Gastrointestinal Surg & Liver Transplantat Unit, I-20133 Milan, Italy

来源：

CANCERS | 2021年 / 13卷 / 11期

关键词：

gastric cancer; microsatellite instability; pre-operative treatment; PD-L1; CTLA4; non-operative management; MISMATCH REPAIR DEFICIENCY; NIVOLUMAB PLUS IPILIMUMAB; ADJUVANT CHEMOTHERAPY; PD-1; BLOCKADE; OPEN-LABEL; SURGERY; BENEFIT; TUMORS;

D O I：

10.3390/cancers13112839

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary The status of microsatellite instability (MSI-H) in gastric or gastroesophageal junction cancer (GC/GEJC) patients eligible for radical surgery proved to be prognostic for an improved survival outcome and predictive for poor/no benefit from the combination of adjuvant/peri-operative chemotherapy. MSI-H tumors display a high sensitivity to immunotherapy and exploratory studies showed that a pre-operative treatment with immune-checkpoint inhibitors may achieve elevated rates of pathological complete responses. The ongoing proof-of-concept INFINITY study is aimed at investigating the role of the combo-immunotherapy durvalumab plus tremelimumab as a neoadjuvant or potentially definitive treatment (avoiding surgery in case of complete clinical response) for MSI-H resectable GC/GEJC patients. In resectable gastric or gastroesophageal junction cancer (GC/GEJC), the powerful positive prognostic effect and the potential predictive value for a lack of benefit from the combination of adjuvant/peri-operative chemotherapy for the MSI-high status was demonstrated. Given the high sensitivity of MSI-high tumors for immunotherapy, exploratory trials showed that combination immunotherapy induces a high rate of complete pathological response (pCR), potentially achieving cancer cure without surgery. INFINITY is an ongoing phase II, multicentre, single-arm, multi-cohort trial investigating the activity and safety of tremelimumab and durvalumab as neoadjuvant (Cohort 1) or potentially definitive (Cohort 2) treatment for MSI-high/dMMR/EBV-negative, resectable GC/GEJC. About 310 patients will be pre-screened, to enroll a total of 31 patients, 18 and 13 in Cohort 1 and 2, at 25 Italian Centres. The primary endpoint of Cohort 1 is rate of pCR (ypT0N0) and negative ctDNA after neoadjuvant immunotherapy, of Cohort 2 is 2-year complete response rate, defined as absence of macroscopic or microscopic residual disease (locally/regionally/distantly) at radiological examinations, tissue and liquid biopsy, during non-operative management without salvage gastrectomy. The ongoing INFINITY proof-of-concept study may provide evidence on immunotherapy and the potential omission of surgery in localized/locally advanced GC/GEJC patients selected for dMMR/MSI-high status eligible for radical resection.

引用

页数：15

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