scholarly journals The Agnostic Role of Site of Metastasis in Predicting Outcomes in Cancer Patients Treated with Immunotherapy

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 203 ◽  
Author(s):  
Andrea Botticelli ◽  
Alessio Cirillo ◽  
Simone Scagnoli ◽  
Bruna Cerbelli ◽  
Lidia Strigari ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Predictive Factor ◽  
Univariate Analysis ◽  
Eastern Cooperative Oncology Group ◽  
Tumor Burden ◽  
Clinicopathological Parameters ◽  
Anatomical Site ◽  
Metastatic Sites ◽  
Ecog Ps

Immune checkpoint inhibitors have revolutionized treatment and outcome of melanoma and many other solid malignancies including non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Unfortunately, only a minority of patients have a long-term benefit, while the remaining demonstrate primary or acquired resistance. Recently, it has been demonstrated that the prevalence of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) varies based on the anatomical site of metastases. In particular, liver seems to have more immunosuppressive microenvironment while both the presence of lymph nodal disease and lung metastases seem to have the highest prevalence of PD-L1 and TILs. The aim of the present study is to investigate the possible role of site of metastases as a predictive factor for response or resistance to immunotherapy in several types of cancer. In this multicenter retrospective study, we enrolled patients with metastatic NSCLC, melanoma, RCC, urothelial, merkel carcinoma, and colon cancer who received immunotherapy from April 2015 to August 2019. Major clinicopathological parameters were retrieved and correlated with patients’ survival outcomes in order to assess their prognostic value and build a useful tool to assist in the decision-making process. A total of 291 patients were included in this study. One hundred eighty-seven (64%) patients were male and 104 (36%) female. The tumor histology was squamous NSCLC in 56 (19%) patients, non-squamous NSCLC in 99 (34%) patients, melanoma in 101 (35%) patients, RCC in 28 (10%) patients, and other tumors in the remaining 7 (2%) patients. The number of metastatic sites was 1 in 103 patients (35%), 2 in 104 patients (36%) and 3 in 84 patients (29%). Out of 183 valuable patients, the entity of response was complete response (CR), partial response (PR), stable disease (SD), and progression disease (PD) in 15, 53, 31, and 79 patients, respectively. Using an univariate analysis (UVA), tumor burden (p = 0.0004), the presence of liver (p = 0.0009), bone (p = 0.0016), brain metastases (p < 0.0001), the other metastatic sites (p = 0.0375), the number of metastatic sites (p = 0.0039), the histology (p = 0.0034), the upfront use of immunotherapy (p = 0.0032), and Eastern Cooperative Oncology Group (ECOG) Perfomance status (PS) ≥ 1 (p < 0.0001) were significantly associated with poor overall survival (OS). Using a multivariate analysis (MVA) the presence of liver (p = 0.0105) and brain (p = 0.0026) metastases, the NSCLC diagnosis (p < 0.0001) and the ECOG PS (p < 0.0001) resulted as significant prognostic factors of survival. Regarding the progression free survival (PFS), using a UVA of the tumor burden (p = 0.0004), bone (p = 0.0098) and brain (p = 0.0038) metastases, the presence of other metastatic sites (p = 0.0063), the number of metastatic sites (p = 0.0007), the histology (p = 0.0007), the use of immunotherapy as first line (p = 0.0031), and the ECOG PS ≥ 1 (p ≤ 0.0001) were associated with a lower PFS rate. Using an MVA, the presence of brain (p = 0.0088) and liver metastases (p = 0.024) and the ECOG PS (p < 0.0001) resulted as predictors of poor PFS. Our study suggests that the site of metastases could have a role as prognostic and predictive factor in patients treated with immunotherapy. Indeed, regardless of the histology, the presence of liver and brain metastases was associated with a shorter PFS and OS, but these results must be confirmed in further studies. In this context, a deep characterization of microenvironment could be crucial to prepare patients through novel strategies with combination or sequential immunotherapy in order to improve treatment response.

Update of the FL2000 randomized trial combining rituximab to CHVP-Interferon in follicular lymphoma (FL) patients (pts)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7508-7508 ◽  
Author(s):  
C. Foussard ◽  
N. Mounier ◽  
A. Van Hoof ◽  
V. Delwail ◽  
O. Casasnovas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Study ◽  
Bone Marrow Involvement ◽  
Risk Groups ◽  
Tumor Burden ◽  
Event Free Survival ◽  
Free Survival ◽  
High Tumor Burden ◽  
Ecog Ps

7508 Background: The GELA-GOELAMS FL2000 trial investigated the role of rituximab in the first line treatment of FL pts. Methods: This prospective randomized study compared the CHVP regimen (12 courses) +18 months α2b-IFN (CHVP-I) to 6 CHVP courses combined with 6 rituximab infusions + 18 months IFN (R-CHVP-I). The primary endpoint was event-free survival (EFS). Inclusion criteria consisted in untreated stage II-IV FL pts; 18–75 years old; with a high tumor burden defined by at least one of the following criteria: B symptoms, ECOG PS>1, LDH>normal value, β2-microglobulin ≥3 mg/L, largest tumor ≥7 cm, 3 distinct nodes ≥3 cm, serous effusion, compression or symptomatic spleen enlargement. Results: From 05/00 until 05/02, 358 eligible pts were randomized (CHVP-I 183 pts and R-CHVP-I 175 pts) with the following characteristics: M/F = 1; median age = 60 years [25–75]; ECOG > 1 = 8%; B symptoms = 27%; AA stage > II = 87%; bone marrow involvement = 58%; β2-m ≥3 mg/L = 31%; LDH > N = 37%; Hb <12 g/dL = 18%; FLIPI score ≥3 in 57% of the pts. The first analysis [ASH 2004] showed a significant better treatment response in R-CHVP-I as compared to CHVP-I and a improvement of event free survival (EFS) in the R-CHVP-I arm (Log-Rang, P = .003). As initially planned, a second analysis on all pts has now been performed with a median follow-up of 3½ years, all pts with data >01/01/05. The median EFS for the whole population has not yet been reached. In the CHVP-I arm, median EFS was 3 years and 46% of the pts are event-free at 42 months (mo.). In contrast, the median has not been reached in the R-CHVP-I arm and the EFS is 67% at 42 mo. (P < .0001). This improvement in EFS was found both in the 150 pts with a low or intermediate FLIPI score (P = .019) and in those (n = 201) with a high score (P = .0005). When considering the 230 pts responders at the end of 18 mo. of therapy, 42 mo. EFS is 62% in CHVP-I arm versus 81% in R-CHVP-I arm (P = .002). Finally, the overall survival at 42 mo. of patients in the CHVP-I arm is of 84% versus to 91% in the R-CHVP-I arm (P = .029) with a reduction of death risk by approximately 2 (RR = 0.55). Conclusions: These results demonstrate that rituximab combined with CHVP-I has a durable benefit, in all FLIPI risk groups, allows to reduce the duration of chemotherapy and improves overall survival in high-tumor burden FL pts. [Table: see text]

Role of progesterone receptor status (PR) as predictive factor of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer (BC) patients (pts)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 637-637
Author(s):  
J. M. Perez Garcia ◽  
C. Saura ◽  
E. Muñoz ◽  
G. Sanchez-Olle ◽  
P. Gomez ◽  
...  
Keyword(s):  
Predictive Factor ◽  
Multivariate Analyses ◽  
Histological Grade ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Complete Response ◽  
Her 2 ◽  
Few Data

637 Background: While estrogen receptor (ER) negativity has been consistently associated to higher pCR rates after NACT in BC, few data regarding the association of PR with pCR has been reported. PR positivity has been related to taxol resistance in in vitro chemosensitivity assays. Our aim was to investigate the putative role of PR in the prediction of pCR in a cohort of BC pts receiving NACT. Methods: Medical reports of all pts receiving NACT and breast surgery between 2004 and 2006 in our institution were reviewed. Baseline clinical and histological features, along with type of preoperative therapy were examined as variables for association with pCR (no invasive tumor in breast and axilla) using univariate and multivariate analyses. Results: 128 pts were included. 73.4% received anthracycline and taxanes (A&Tx) based CT and 9.4% also received trastuzumab (T). PR+ (≥ 10%) was significantly associated with low histological grade (HG), low Ki67 (<10%), HER-2- (Herceptest 0,1,or 2 with FISH-) and ER+ (≥10%). Overall pCR rate was 18.8%. No PR+ patient achieved pCR. In univariate analysis, high HG, ER-, PR-, HER-2-, high Ki67, T therapy, and number of CT cycles were significantly associated with pCR. In multivariate analysis only HER-2 and PR status were statistically significant. Similarly, PR and HER-2 status were independently related to pCR in the subgroup of pts receiving A&Tx (N = 94, 20.2%pCR). In the HER-2- subgroup (n = 89, 9%pCR) only ER independently predicted pCR, while in the HER-2+ subgroup (n = 33, 42.4%pCR, 57.1%pCR with T), both PR- and T therapy were the only predictive factors for pCR in the univariate and multivariate analyses. When the 24 HER-2+ pts treated with A&Tx (23 taxol/1 taxotere) ± T were separately analyzed, only PR retained statistical significance in the multivariate model. Conclusions: In our cohort of BC pts treated with NACT, PR status independently predicts pCR in the whole population as well as in the A&Tx-treated and in the HER-2+ subgroups. In the HER-2+ pts receiving A&Tx ± T PR negativity was the only factor associated with pCR. PR status merits further investigation as a predictive factor for pCR to NACT, in particular in HER-2+ population. No significant financial relationships to disclose.

Sarcoligo: Impact of local ablative treatment of oligometastatic sarcomas on overall survival.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10042-10042
Author(s):  
Juliette Thariat ◽  
Laurence Moureau-Zabotto ◽  
Nicolas Penel ◽  
Antoine Italiano ◽  
Jacques-Olivier Bay ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Metastases ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Locoregional Treatment ◽  
Metastatic Sites ◽  
The Impact

10042 Background: 40-50% of sarcomas become metastatic. Median survival of metastatic patients has improved over time. The probably multifactorial reasons for such improvement are not fully clear. Noteworthy, for patients with a controlled primary and a limited number of lung metastases, complete resection of their metastases yields survival rates of up to 40% at three years. Advances in surgery, radiotherapy and radiofrequency have fostered the use of local treatments for various metastatic sites (lung, liver, spine...). Methods: A multicentric retrospective study of the Groupe Sarcome Francais (GSF-GETO); approved by the nationally-review board and ethical committee, was conducted to assess the impact of local ablative treatment on overall survival. Patients who had had oligometastases (any site, 1-5 synchronous metastases) at diagnostic or during the course of disease between 2000 and 2010 were included. Results: Median age of the 243 oligometastatic sarcoma patients was 53 years-old (11-86). Patients had grade I, II and III in 7.5%, 29.6% and 63.3% of cases, respectively with various histologies. 69% of patients underwent local ablative treatment of metastases. Median follow-up was 59 months (4-212) for living patients. Median overall survival was 51 months (1-348). On univariate analysis, grade, histology, absence of chemotherapy, local ablative treatment (surgery, irradiation, radiofrequency or chemoembolisation) correlated with survival but not age or site of oligometastasis. On multivariate analyses, grade (hazard ratio HR 0.12 [CI95 0.3-0.6]) and local ablative treatment (HR 3.8 [CI95 2.1-7.1]) remained significant. Conclusions: Local ablative treatment of metastases is associated with better survival in sarcoma patients with oligometastatic disease. The role of the locoregional treatment of metastases and its impact on quality of life should be assessed prospectively.

Prognostic factors and validation of prognostic nomograms in patients (pts) treated with three targeted therapies (TTs) for metastatic renal cell carcinoma (mRCC): Results from an Italian survey.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 470-470
Author(s):  
Roberto Iacovelli ◽  
Michele Milella ◽  
Matteo Santoni ◽  
Giuseppe Di Lorenzo ◽  
Cinzia Ortega ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Survival Data ◽  
Demographic Data ◽  
Univariate Analysis ◽  
Cleveland Clinic ◽  
Relative Survival ◽  
Prognostic Role ◽  
Third Line ◽  
Metastatic Sites ◽  
Ecog Ps

470 Background: Outcomes of pts treated with three TTs for mRCC have not been well characterized. Survival data as well as existing prognostic criteria in this population were evaluated. Methods: Pts with clear-cell mRCC who received 3 TTs were included. A questionnaire was send to main Italian centers involved in the treatment of mRCC. Demographic data, history of RCC, type, and length of first-, second-, and third-lines were collected. Values of serum Hb, PLT, neutrophils, LDH and Ca, ECOG-PS, previous RT and number of metastatic sites >2 before the start of third-line were evaluated. Cleveland Clinic, French, Heng, and MSKCC scores and relative survival were calculated. Results: Following the screening of 1,905 pts, 252 (13%) with 3 TTs were identified. The median age was 60 yrs (range 52-68), 73% were male, 96% had nephrectomy and 38% were metastatic at diagnosis. At first-line, the Motzer class was good, intermediate, and poor in 48%, 47%, and 5% of pts, respectively. The median OS from the start of third-line was 14.3 mos (95%CI, 10.1–18.6). Rate and survival by prognostic group according to each classification are reported in table below. When prognostic factors were considered separately, at the univariate analysis ECOG-PS≥2, Hb<LLN, LDH>1.5ULN, Ca>ULN; PLT>ULN; Neu>ULN, and sites of disease >2 had negative prognostic role. Multivariate analysis shows an independent prognostic role only for ECOG-PS≥2 (HR: 1.8; 95%CI: 1.1–2.8), Hb<LLN (HR: 1.8; 95%CI: 1.2–2.6) and neu>ULN (HR: 2.1; 95%CI: 1.2–3.8). Pts were stratified in 3 groups according to the presence of none, 1 or ≥2 prognostic factors. The median OS was 20.3, 13.6 and 7.8 months, respectively (p<0.001). Conclusions: Current nomograms are able to predict survival in patients with mRCC before the third-line with TT. Neutrophils, hemoglobin and ECOG-PS were the most important prognostic factors. [Table: see text]

Efficacy of cytotoxic agents after progression of anti-PD-(L)1 antibody for pretreated metastatic gastric cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 152-152
Author(s):  
Kyoko Kato ◽  
Yukiya Narita ◽  
Seiichiro Mitani ◽  
Kazunori Honda ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Univariate Analysis ◽  
Patient Characteristics ◽  
Metastatic Gastric Cancer ◽  
Cytotoxic Agents ◽  
Her2 Positive ◽  
Period Range ◽  
Median Period ◽  
Metastatic Sites ◽  
Ecog Ps

152 Background: The efficacy of anti-PD-1 antibody for metastatic gastric cancer (mGC) was revealed. In non-small cell lung cancer (NSCLC), it was reported that overall response rate (ORR) in patients (pts) treated with chemotherapy (CTx) after immunotherapy exposure was higher than historical data from the pre-anti-PD-(L)1 era. The purpose of this retrospective study was to evaluate whether CTx improved efficacy outcomes after exposure anti-PD(L)1 antibody in mGC. Methods: We investigated retrospectively clinical characteristics at baseline of mGC pts who received CTx after progression of anti-PD-(L)1 antibody between April 2014 and August 2017. Anti-PD-(L)1 antibody was adapted as third- or later-line therapy. Pts fulfilled following criteria: histologically proven adenocarcinoma; ECOG PS 0-2; adequate organ functions; and received CTx including fluoropyrimidines (FU), platinum, and taxane or irinotecan. We evaluated efficacy outcomes, including ORR, disease control rate (DCR), time to treatment failure (TTF), and overall survival (OS). Results: Out of 40 treated with anti-PD-(L)1 antibody, 15 pts were included. Patient characteristics were as follows: median age (range), 67 (46-83) years; male/female, 13/2; ECOG PS (0/1/2), 5/8/2; HER2 positive, 8; histology (differentiated/undifferentiated), 10/5; metastatic lesions (peritoneum/liver/lung), 4/8/3; number of metastatic sites (1/≥2), 2/13; number of prior CTx regimens (3/4/5), 2/9/4; median period (range) from first line CTx, 30.7 (12.7-68.1) months; and CTx regimens (FU+oxaliplatin/taxane/irinotecan), 10/3/2. ORR, DCR, median TTF, and OS were 33% (95% CI, 15.2-58.3), 87% (95% CI, 62.1-96.3), 3.5 (95% CI, 1.6-4.4) months, and 7.6 (95% CI, 4.4-8.5) months, respectively. There were no predictive and prognostic factors associated with ORR, TTF, and OS on univariate analysis. At the beginning of CTx, 4 pts had immune-related adverse events (irAEs), but these were manageable and no new irAEs appeared during CTx. Conclusions: Our data support further evaluation of the use of CTx after progression of anti-PD-L 1 antibody, even in heavily pretreated mGC pts. Updated results will be presented.

Exploratory analysis of the effect of FTD/TPI in patients treated in RECOURSE by prognostic factors.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 677-677 ◽  
Author(s):  
Josep Tabernero ◽  
Alberto F. Sobrero ◽  
Christophe Borg ◽  
Atsushi Ohtsu ◽  
Robert J. Mayer ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Good Prognosis ◽  
Tumor Burden ◽  
Phase Iii ◽  
Kras Status ◽  
Indolent Disease ◽  
Metastatic Sites ◽  
Ecog Ps

677 Background: The Phase III RECOURSE trial, in patients (pts) with metastatic colorectal cancer (mCRC) refractory to standard therapies, demonstrated that trifluridine/tipiracil (FTD/TPI) significantly extended overall survival (OS) and progression-free survival (PFS) versus placebo in all subgroups, regardless of age, geographical origin, or KRAS status, with acceptable safety. Literature reports have shown optimal benefit for pts with low tumor burden (< 3 metastatic sites), indolent disease (≥ 18 mo since diagnosis of first metastasis), ECOG PS 0-1, and no liver metastasis when treated in late line mCRC. Methods: This exploratory post hoc analysis of RECOURSE (all ECOG 0-1) compared pts on FTD/TPI or placebo with good prognostic characteristics (GPC; low tumor burden and indolent disease) and poor prognostic characteristics (PPC; high tumor burden and/or aggressive disease). These subgroups were then analyzed by liver metastasis at baseline, ECOG PS, KRAS status and age. Results: Baseline characteristics were generally similar between the two groups. GPC placebo pts performed better than the PPC placebo pts, but worse than the GPC pts treated with FTD/TPI. GPC pts treated with FTD/TPI showed median OS of 9.3 mo versus 5.3 mo in PPC pts (HR 0.46; 95% CI: 0.37, 0.57; p < 0.0001); there was a similar effect for PFS. GPC pts had significantly better mOS and mPFS regardless of age (≥ 65 vs. < 65 y), ECOG PS (0–1), KRAS status (mutant vs. wildtype), and liver metastasis (y/n). No liver metastasis was the best prognostic factor: mOS in such pts treated with FTD/TPI was 16.4 mo and 7.6 mo in the GPC (n = 97) and PPC (n = 35) groups, respectively (HR 0.42; 95% CI: 0.24, 0.74; p < 0.0019); there was a similar effect for PFS. Pts with ECOG PS 0 at baseline remained PS 0-1 at discontinuation in 96% of the GPC group. Conclusions: Low tumor burden and indolent disease indicate good prognosis in late line mCRC. Pts with no liver metastasis have the best prognosis and are likely to have longer OS. GPCs might explain the percentage of long-term responders on FTD/TPI in RECOURSE. Maintenance of ECOG PS 0–1 during treatment is crucial in the continuum of care, allowing pts to benefit from further treatment options. Clinical trial information: NCT01607957.

scholarly journals RADI-17. Outcomes for patients with triple negative breast cancer treated with upfront stereotactic radiosurgery for brain metastases

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii21-iii21
Author(s):  
Ran An ◽  
Yan Wang ◽  
Fuchenchu Wang ◽  
Akshara Singareeka Raghavendra ◽  
Chao Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Univariate Analysis ◽  
Karnofsky Performance Score ◽  
Risk Of Death ◽  
Metastatic Sites

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype with high propensity of developing brain metastases (BM). Clinical outcomes and prognostic factors after stereotactic radiosurgery (SRS) for BM were not well defined. Methods We identified 57 consecutive TNBC patients (pts) treated with single fraction SRS for BM during 05/2008–04/2018. Overall survival (OS) from BM diagnosis and freedom from BM progression (FFBMP) after initial SRS were evaluated. BM progression was defined as local and/or distant brain failure (LBF, DBF) after SRS. Kaplan-Meier analyses and Cox proportional hazard regression were used to estimate survival outcomes and identify prognostic factors. Results The median time to BM development from TNBC diagnosis was 23.7 months (mo) (range 0.7‒271.1). Median OS was 13.1 mo (95%CI 8.0‒19.5). On univariate analysis, Karnofsky performance score (KPS) &gt;70 (p=0.03), number of BMs &lt;3 (p=0.016), and BM among the first metastatic sites (p=0.04) were associated with longer OS. On multivariate analysis, KPS ≤70 was associated with higher risk of death (HR 3.0, p=0.03). Of 46 pts with adequate imaging follow-up, 29 (63%) had intracranial progression with a median FFBMP of 7.4 mo (95% CI 5.7–12.7). At 12 mo the estimated cumulative DBF rate was 61.1% (95%CI 40.8%–74.4%) and LBF rate was 17.8% (95%CI 2%–31.1%). Number of BMs (≥3 vs &lt;3) was not associated with FFBMP (p=0.7). Of the 29 pts with BM progression, additional radiation therapy (RT) (vs. no RT) was associated with improved survival (21.7 vs. 7.0 mo, p&lt;0.0001). Conclusions TNBC pts with BM treated with SRS had an OS of 13.1 mo and FFBMP of 7.4 mo. Good KPS was an independent prognostic factor for OS. Further studies with more pts or conducted prospectively are needed to better understand and to improve treatment outcomes in this pt population.

scholarly journals Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Jose Pablo Leone ◽  
Kyrre E. Emblem ◽  
Michelle Weitz ◽  
Rebecca S. Gelman ◽  
Bryan P. Schneider ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Group Performance ◽  
Brain Mri ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Her2 Positive ◽  
Breast Cancer Brain Metastases ◽  
Ecog Ps ◽  
Mri Changes

Abstract Background We aimed to examine the safety and efficacy of bevacizumab and carboplatin in patients with breast cancer brain metastases. Methods We enrolled patients with breast cancer and > 1 measurable new or progressive brain metastasis. Patients received bevacizumab 15 mg/kg intravenously (IV) on cycle 1 day 1 and carboplatin IV AUC = 5 on cycle 1 day 8. Patients with HER2-positive disease also received trastuzumab. In subsequent cycles, all drugs were administered on day 1 of each cycle. Contrast-enhanced brain MRI was performed at baseline, 24–96 h after the first bevacizumab dose (day + 1), and every 2 cycles. The primary endpoint was objective response rate in the central nervous system (CNS ORR) by composite criteria. Associations between germline VEGF single nucleotide polymorphisms (rs699947, rs2019063, rs1570360, rs833061) and progression-free survival (PFS) and overall survival (OS) were explored, as were associations between early (day + 1) MRI changes and outcomes. Results Thirty-eight patients were enrolled (29 HER2-positive, 9 HER2-negative); all were evaluable for response. The CNS ORR was 63% (95% CI, 46–78). Median PFS was 5.62 months and median OS was 14.10 months. As compared with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, patients with ECOG PS 1–2 had significantly worse PFS and OS (all P < 0.01). No significant associations between VEGF genotypes or early MRI changes and clinical outcomes were observed. Conclusions The combination of bevacizumab and carboplatin results in a high rate of durable objective response in patients with brain metastases from breast cancer. This regimen warrants further investigation. Trial registration NCT01004172. Registered 28 October 2009.

Tumor burden as an independent prognostic factor in metastatic renal cell carcinoma (mRCC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 397-397 ◽  
Author(s):  
Bernard J. Escudier ◽  
Roberto Iacovelli ◽  
Emilie Lanoy ◽  
Laurence Albiges ◽  
Karim Fizazi
Keyword(s):  
Proportional Hazards Model ◽  
Performance Status ◽  
Tumor Burden ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Prognostic Role ◽  
Risk Class ◽  
Final Population ◽  
Ecog Ps

397 Background: During the last ten years, several classifications have been used to assess the prognosis in mRCC. In none of them, tumor burden (TB) has been considered. This study investigates the prognostic role of baseline TB in terms of progression free survival (PFS) and overall survival (OS), in patients with mRCC. Methods: All patients with clear cell mRCC enrolled in our center, in 2 second-line trials, post cytokine, with sunitinib and sorafenib or placebo (Escudier JCO 2009, Escudier NEJM 2007), were selected for this analysis. TB was defined as the sum of the longest unidimensional diameter of each target lesions assessed using RECIST criteria. PFS and OS were estimated using Kaplan-Meier method and compared using the log-rank test. Association between TB and PFS or OS was evaluated using the Cox proportional hazards model. Multivariable analyses were adjusted for modified MSKCC risk class and treatment. Non-parametric Spearman rank test (rs) was used to assess the correlations between TB and MSKCC risk groups or ECOG Performance Status (PS). Results: Final population included 124 patients: 66% received sorafenib or sunitinib and 34% received placebo; median follow up was 80.1 months (IQR: 68.8 – 88.0). Baseline TB was divided into 3 tertiles (1.3 - 9.4 cm; 9.5 - 19.0 cm; 19.1 - 47.3 cm). TB was related to PFS and OS and, when adjusting for modified MSKCC risk class and treatment, these associations remained significant: each 1 cm increase in TB increased the progression risk by 5% (HR: 1.05; 95%CI, 1.02 – 1.07; p < 0.0001) and the death risk by 5% (HR: 1.05; 95%CI, 1.03 – 1.08; p < 0.0001). OS decreased with TB: the median tertiles OS values were: 42.1 months (95%CI: 24.0 – 60.2), 20.1 months (95%CI: 14.5 – 25.7), and 11.2 months (95%CI: 4.8 – 17.6), respectively (p < 0.0001, figure 2). The TB was positively related to ECOG PS (rs = 0.357; p < 0.0001) and to MSKCC risk score (rs = 0.478; p < 0.0001). Patients with higher TB had shorter PFS, shorter OS, poorer MSKCC score and increased ECOG PS. Conclusions: TB is easy to calculate with standard CT and significantly relates to OS and PFS in patients with mRCC. We report for the first time the independent prognostic role of baseline TB in mRCC.

Weighing the role of concomitant medications during PD-1/PD-L1 checkpoint blockade: A preliminary analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15132-e15132
Author(s):  
Alessio Cortellini ◽  
Domenico Mallardo ◽  
Maria Grazia Vitale ◽  
Sergio Bracarda ◽  
Serena Macrini ◽  
...  
Keyword(s):  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Advanced Cancer Patients ◽  
Primary Tumors ◽  
Female Ratio ◽  
Male Female Ratio ◽  
Concomitant Medications ◽  
Metastatic Sites ◽  
Ecog Ps

e15132 Background: The role of concomitant medications, such as steroids, antibiotics and proton pump inhibitors, during immunotherapy has already been investigated, without conclusive results. Methods: This is a multicenter retrospective study, of advanced cancer patients (any histology) treated with anti-PD-1/PD-L1 immunotherapy. Baseline concomitant medications were collected. Results: From June 2014 to November 2019, 277 consecutive patients were evaluated. Median age was 69 years; male/female ratio was 190/87. Primary tumors were: NSCLC (41.9%), melanoma (40.1%), renal cell carcinoma (11.9%) and others (6.1%). 63 patients (22.7%) had ECOG-PS ≥ 2. 120 patients (43.3%) had ≥ 2 metastatic sites. Conclusions: Cancer-related steroids administration, systemic antibiotics, proton pump inhibitors, anticoagulants, opioids, oral anti-diabetics and insulin therapy seem to significantly affect survival in patients receiving PD-1/PD-L1 inhibitors. In interpreting such data, it is important to consider the prevalent role of poor clinical condition. Our preliminary results warrant further investigation in a larger cohort of patients and in a perspective way. [Table: see text]

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