Evaluating the role of FAMIly history of cancer and diagnosis of multiple neoplasms in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: the multicenter FAMI-L1 study

被引:10
作者
Cortellini, Alessio [1 ,2 ]
Buti, Sebastiano [3 ]
Bersanelli, Melissa [3 ,4 ]
Giusti, Raffaele [5 ]
Perrone, Fabiana [3 ]
Di Marino, Pietro [6 ]
Tinari, Nicola [7 ]
De Tursi, Michele [7 ]
Grassadonia, Antonino [7 ]
Cannita, Katia [1 ]
Tessitore, Alessandra [2 ]
Zoratto, Federica [8 ]
Veltri, Enzo [8 ]
Malorgio, Francesco [9 ]
Russano, Marco [10 ]
Anesi, Cecilia [10 ]
Zeppola, Tea [10 ]
Filetti, Marco [5 ]
Marchetti, Paolo [5 ,11 ,12 ,13 ]
Botticelli, Andrea [11 ]
Cappellini, Gian Carlo Antonini [13 ]
De Galitiis, Federica [13 ]
Vitale, Maria Giuseppa [14 ]
Rastelli, Francesca [15 ]
Pergolesi, Federica [15 ]
Berardi, Rossana [16 ]
Rinaldi, Silvia [16 ]
Tudini, Marianna [17 ]
Silva, Rosa Rita [17 ]
Pireddu, Annagrazia [18 ]
Atzori, Francesco [18 ]
Iacono, Daniela [19 ]
Migliorino, Maria Rita [19 ]
Gelibter, Alain [12 ]
Occhipinti, Mario Alberto [12 ]
Martella, Francesco [12 ]
Inno, Alessandro [20 ]
Gori, Stefania [21 ]
Bracarda, Sergio [21 ]
Zannori, Cristina [22 ]
Mosillo, Claudia [22 ]
Parisi, Alessandro [1 ,2 ]
Porzio, Giampiero [1 ,2 ]
Mallardo, Domenico [23 ]
Fargnoli, Maria Concetta [2 ,24 ]
Tiseo, Marcello [3 ,4 ]
Santini, Daniele [10 ]
Ascierto, Paolo A. [23 ]
Ficorella, Corrado [1 ,2 ]
机构
[1] St Salvatore Hosp, Med Oncol, Laquila, Italy
[2] Univ Aquila, Dept Biotechnol & Appl Clin Sci, Laquila, Italy
[3] Univ Hosp Parma, Med Oncol, Parma, Italy
[4] Univ Parma, Dept Med & Surg, Parma, Italy
[5] Azienda Osped Univ St Andrea, UOC Oncol Med, Rome, Italy
[6] SS Annunziata Hosp, Clin Oncol Unit, Chieti, Italy
[7] Univ G DAnnunzio, Dept Med Oral & Biotechnol Sci, Chieti, Italy
[8] Santa Maria Goretti Hosp, Med Oncol, Latina, Italy
[9] Santo Spirito Hosp, Med Oncol, Pescara, Italy
[10] Campus Biomed Univ, Med Oncol, Rome, Italy
[11] Sapienza Univ Rome, Med Oncol, Rome, Italy
[12] Policlin Umberto 1, Med Oncol B, Rome, Italy
[13] IDI IRCCS, Med Oncol, Rome, Italy
[14] Univ Hosp Modena, Med Oncol, Modena, Italy
[15] Fermo Area Vasta 4, Med Oncol, Fermo, Italy
[16] Univ Politecn Marche, Oncol Clin, Ancona, Italy
[17] AV2 Fabriano ASUR Marche, Med Oncol, Fabriano, Italy
[18] Univ Hosp Cagliari, Med Oncol Unit, Cagliari, Italy
[19] St Camillo Forlanini Hosp, Pulm Oncol Unit, Rome, Italy
[20] G Mazzini Hosp, Med Oncol, Teramo, Italy
[21] Sacro Cuore Don Calabria Hosp, Med Oncol Unit, IRCCS, Verona, Italy
[22] Azienda Osped S Maria, Med Oncol, Terni, Italy
[23] IRCCS Fdn G Pascale, Melanoma Canc Immunotherapy & Dev Therapeut Unit, Ist Nazl Tumori, Naples, Italy
[24] San Salvatore Hosp, Dermatol, Laquila, Italy
关键词
Family history of cancer; multiple neoplasms; DDR genes; immune checkpoint inhibitors; immunotherapy; PD-1; CELL LUNG-CANCER; DNA-DAMAGE RESPONSE; ADVERSE EVENTS; ELDERLY-PATIENTS; PD-1; BLOCKADE; ASSOCIATION; NIVOLUMAB; TUMORS; MELANOMA; GENES;
D O I
10.1080/2162402X.2019.1710389
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: We investigate the role of family history of cancer (FHC) and diagnosis of metachronous and/or synchronous multiple neoplasms (MN), during anti-PD-1/PD-L1 immunotherapy. Design: This was a multicenter retrospective study of advanced cancer patients treated with anti-PD-1/PD-L1 immunotherapy. FHC was collected in lineal and collateral lines, and patients were categorized as follows: FHC-high (in case of cancer diagnoses in both the lineal and collateral family lines), FHC-low (in case of cancer diagnoses in only one family line), and FHC-negative. Patients were also categorized according to the diagnosis of MN as follows: MN-high (>2 malignancies), MN-low (two malignancies), and MN-negative. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of immune-related adverse events (irAEs) of any grade were evaluated. Results: 822 consecutive patients were evaluated. 458 patients (55.7%) were FHC-negative, 289 (35.2%) were FHC-low, and 75 (9.1%) FHC-high, respectively. 29 (3.5%) had a diagnosis of synchronous MN and 94 (11.4%) of metachronous MN. 108 (13.2%) and 15 (1.8%) patients were MN-low and MN-high, respectively. The median follow-up was 15.6 months. No significant differences were found regarding ORR among subgroups. FHC-high patients had a significantly longer PFS (hazard ratio [HR] = 0.69 [95% CI: 0.48-0.97], p = .0379) and OS (HR = 0.61 [95% CI: 0.39-0.93], p = .0210), when compared to FHC-negative patients. FHC-high was confirmed as an independent predictor for PFS and OS at multivariate analysis. No significant differences were found according to MN categories. FHC-high patients had a significantly higher incidence of irAEs of any grade, compared to FHC-negative patients (p = .0012). Conclusions: FHC-high patients seem to benefit more than FHC-negative patients from anti-PD-1/PD-L1 checkpoint inhibitors.
引用
收藏
页数:10
相关论文
共 38 条
[1]  
[Anonymous], 2013, Sturdivant RX. Applied Logistic Regression
[2]  
[Anonymous], INT AGENCY RES CANC
[3]   Trends in kidney cancer among the elderly in Denmark, 1980-2012 [J].
Azawi, Nessn H. ;
Joergensen, Simon Moeller ;
Jensen, Niels Viggo ;
Clark, Peter E. ;
Lund, Lars .
ACTA ONCOLOGICA, 2016, 55 :79-84
[4]   Distinctive Features of Melanoma and Its Management in Elderly Patients A Population-Based Study in France [J].
Ciocan, Dragos ;
Barbe, Coralie ;
Aubin, Francois ;
Granel-Brocard, Florence ;
Lipsker, Dan ;
Velten, Michel ;
Dalac, Sophie ;
Truchetet, Francois ;
Michel, Catherine ;
Mitschler, Audrey ;
Arnoult, Gwendoline ;
Buemi, Antoine ;
Dalle, Stephane ;
Bernard, Philippe ;
Woronoff, Anne-Sophie ;
Grange, Florent .
JAMA DERMATOLOGY, 2013, 149 (10) :1150-1157
[5]   Correlations Between the Immune-related Adverse Events Spectrum and Efficacy of Anti-PD1 Immunotherapy in NSCLC Patients [J].
Cortellini, Alessio ;
Chiari, Rita ;
Ricciuti, Biagio ;
Metro, Giulio ;
Perrone, Fabiana ;
Tiseo, Marcello ;
Bersanelli, Melissa ;
Bordi, Paola ;
Santini, Daniele ;
Giusti, Raffaele ;
Grassadonia, Antonino ;
Di Marino, Pietro ;
Tinari, Nicola ;
De Tursi, Michele ;
Zoratto, Federica ;
Veltri, Enzo ;
Malorgio, Francesco ;
Garufi, Carlo ;
Russano, Marco ;
Anesi, Cecilia ;
Zeppola, Tea ;
Filetti, Marco ;
Marchetti, Paolo ;
Berardi, Rossana ;
Rinaldi, Silvia ;
Tudini, Marianna ;
Silva, Rosa Rita ;
Pireddu, Annagrazia ;
Atzori, Francesco ;
Iacono, Daniela ;
Migliorino, Maria Rita ;
Porzio, Gampiero ;
Cannita, Katia ;
Ficorella, Corrado ;
Buti, Sebastiano .
CLINICAL LUNG CANCER, 2019, 20 (04) :237-+
[6]   A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable [J].
Cortellini, Alessio ;
Bersanelli, Melissa ;
Buti, Sebastiano ;
Cannita, Katia ;
Santini, Daniele ;
Perrone, Fabiana ;
Giusti, Raffaele ;
Tiseo, Marcello ;
Michiara, Maria ;
Di Marino, Pietro ;
Tinari, Nicola ;
De Tursi, Michele ;
Zoratto, Federica ;
Veltri, Enzo ;
Marconcini, Riccardo ;
Malorgio, Francesco ;
Russano, Marco ;
Anesi, Cecilia ;
Zeppola, Tea ;
Filetti, Marco ;
Marchetti, Paolo ;
Botticelli, Andrea ;
Cappellini, Gian Carlo Antonini ;
De Galitiis, Federica ;
Vitale, Maria Giuseppa ;
Rastelli, Francesca ;
Pergolesi, Federica ;
Berardi, Rossana ;
Rinaldi, Silvia ;
Tudini, Marianna ;
Silva, Rosa Rita ;
Pireddu, Annagrazia ;
Atzori, Francesco ;
Chiari, Rita ;
Ricciuti, Biagio ;
De Giglio, Andrea ;
Iacono, Daniela ;
Gelibter, Alain ;
Occhipinti, Mario Alberto ;
Parisi, Alessandro ;
Porzio, Giampiero ;
Fargnoli, Maria Concetta ;
Ascierto, Paolo Antonio ;
Ficorella, Corrado ;
Natoli, Clara .
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2019, 7
[7]   Family history of cancer and DNA damage response genes: Two sides of the same coin? [J].
Cortellini, Alessio ;
Bersanelli, Melissa ;
Ficorella, Corrado ;
Buti, Sebastiano .
THORACIC CANCER, 2019, 10 (02) :401-401
[8]   Family history of cancer as surrogate predictor for immunotherapy with anti-PD1/PD-L1 agents: preliminary report of the FAMI-L1 study [J].
Cortellini, Alessio ;
Bersanelli, Melissa ;
Buti, Sebastiano ;
Gambale, Elisabetta ;
Atzori, Francesco ;
Zoratto, Federica ;
Parisi, Alessandro ;
Brocco, Davide ;
Pireddu, Annagrazia ;
Cannita, Katia ;
Iacono, Daniela ;
Migliorino, Maria R. ;
Gamucci, Teresa ;
De Tursi, Michele ;
Sidoni, Tina ;
Tiseo, Marcello ;
Michiara, Maria ;
Papa, Anselmo ;
Angius, Gesuino ;
Tomao, Silverio ;
Fargnoli, Maria C. ;
Natoli, Clara ;
Ficorella, Corrado .
IMMUNOTHERAPY, 2018, 10 (08) :643-655
[9]  
COX DR, 1972, J R STAT SOC B, V34, P187
[10]   Potent immunogenicity in BRCA1-mutated patients with high-grade serous ovarian carcinoma [J].
Dai, Ying ;
Sun, Chengdu ;
Feng, Yi ;
Jia, Qingzhu ;
Zhu, Bo .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2018, 22 (08) :3979-3986