Biomolecular, biochemical, and radiologic evaluation of patients on anti-VEGF treatment for mCRC.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 556-556
Author(s):  
L. Rossi ◽  
E. Veltri ◽  
M. Di Seri ◽  
S. Vari ◽  
M. Colonna ◽  
...  
Keyword(s):  
Ct Scan ◽  
Clinical Response ◽  
Tumor Markers ◽  
Objective Response ◽  
Hepatic Metastases ◽  
Response To Treatment ◽  
First Line ◽  
Ras Mutations ◽  
Ras Status ◽  
Metastatic Sites

556 Background: K-ras mutation is a negative predictor of clinical benefit (CB) from anti-EGFR treatment in mCRC. Bevacizumab combined with chemotherapy prolongs both PFS and OS in first-line treatment of mCRC. Previously data suggested that this results are independent of K-ras status. We conducted a study to investigate the CB of Bevacizumab in treatment of mCRC according to K-ras status and to evaluate timing of response to treatment trough the correlation between tumor markers values and clinical responses. Finally we evaluated CB in patients affected by mCRC with only hepatic metastases vs patients with multiple metastasis sites. Methods: 82 patients were enrolled and underwent first-line chemotherapy with Folfiri or FolFoX and bevacizumab. Tissue samples were analyzed for DNA sequencing in order to identify K-ras mutations in codons 12 and 13. Before therapy all patients were investigated with CT scan and with a blood sample to define tumor markers values; a new evaluation of tumor markers after 2 months of chemotherapy was performed and a CT scan after 3 months. Results: An overall objective response rate (RR) of 40% and a CB of 79% were obtained, with a correlation between tumor markers values and clinical response of 89%. 49% of population presented only hepatic metastases while other 51% showed multiple metastatic sites. RR in exclusive hepatic metastatic group was 45% vs 33% multiple metastatic sites group, CB was 90% vs 66% respectively. No grade 3 or 4 bevacizumab associated toxicity was showed in patients. K-ras mutations were investigated in 75 of 82 patients. 49 patients were wild-type (wt 65%) while 26 patients were mutated (mut 35%). RR in wt group was 45% vs 35% in mut group, while CB was 82% vs 81% respectively. Correlation between tumor markers values and clinical response was 90% in wt group vs 93% in mut group. Conclusions: RR in two K-ras groups was different with an advantage in K-ras wt group, but this difference does not observe in CB. Bevacizumab provides significant RR and CB after a short time of treatment and tumor markers values could be an optimal correlative parameters of early clinical response. Bevacizumab provides significant CB in patients with only hepatic metastases vs patients with multiple metastatic sites. No significant financial relationships to disclose.

Impact of gemcitabine (G) on the activity of first-line chemotherapy in non-small cell lung cancer (NSCLC): A meta-analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7138-7138
Author(s):  
G. L. Pappagallo ◽  
O. Belvedere ◽  
O. Vinante ◽  
F. Grossi
Keyword(s):  
Meta Analysis ◽  
Performance Status ◽  
Objective Response ◽  
Response To Treatment ◽  
Third Generation ◽  
First Line ◽  
Significant Difference ◽  
Nsclc Patients ◽  
The Impact ◽  
Line Chemotherapy

7138 Background: A two-drug platinum-based regimen in which cisplatin or carboplatin is combined with a third-generation agent (i.e. paclitaxel, vinorelbine, docetaxel, or G) is the standard first-line treatment for NSCLC patients with good performance status. Encouraging results have recently been reported for nonplatinum regimens composed of two third-generation drugs. Methods: To assess the impact of G on the activity of first-line chemotherapy in NSCLC, we carried out a meta-analysis on data from 4,362 NSCLC patients who were enrolled in 11 randomized trials comparing a G-containing vs. G-free new generation regimens. We constructed 2x2 tables using response to treatment data. For trials with more than one eligible G-free comparator arm, individual comparisons between the G-based treatment arms and each of the comparator arms were analyzed. A general variance-based method was used to estimate the pooled odds ratio (OR) and 95% confidence interval (CI). We assessed for heterogeneity among the trials based on standard methods. Results: Sixteen comparisons contributed to this analysis. G-containing regimens included: G+cisplatin (894), G+docetaxel (565), G+paclitaxel (200 patients), G+vinorelbine (157), G+carboplatin (49). G-free regimens included: vinorelbine+cisplatin (866), carboplatin+paclitaxel (539), docetaxel+cisplatin (494), cisplatin+paclitaxel (439), vinorelbine+carboplatin (159). Comparing G-containing vs. G-free regimens, the OR for progression was 0.867 (CI 95% 0.770–0.977; p = 0.019), with heterogeneity chi-square 11.639 (p = 0.71). No significant difference was observed for complete (OR 0.909, CI 95% 0.556–1.487; P = 0.707) and overall (complete + partial) response (OR 0.987, CI 95% 0.881–1.106; P = 0.819). Conclusions: These data demonstrate that the progression of disease is more likely in patients treated with G-free doublets. Further analyses are required to address whether disease control (objective response + stable disease) is associated with a survival benefit and may therefore be used as a surrogate end point for survival in chemotherapy trials of NSCLC. No significant financial relationships to disclose.

Doxorubicin, cisplatin, and ifosfamide (API) as first-line therapy for relapsed or metastatic uterine leiomyosarcoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10098-10098
Author(s):  
Julien Hadoux ◽  
Annie Rey ◽  
Pierre Duvillard ◽  
Catherine Lhomme ◽  
Corinne Balleyguier ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Response Rate ◽  
Objective Response ◽  
Local Relapse ◽  
High Rate ◽  
Physiological Age ◽  
Uterine Leiomyosarcoma ◽  
First Line ◽  
First Line Therapy ◽  
Metastatic Sites

10098 Background: Uterine leiomyosarcomas (ULMS) are rare gynecologic malignancies characterized by a poor prognosis due to a high rate of local and metastatic recurrences. Chemotherapy (CT) with doxorubicin or ifosfamide or both is associated with a 10 to 30% objective response rate (ORR) and a cisplatin-based multiCT approach achieved a good response rate (DECAV therapy: API + dacarbazine + vindesine, 54% ORR in uterine sarcomas), though toxic. We aimed to determine efficacy and toxicity of doxorubicin, cisplatin and ifosfamide (API) combination as first line treatment of metastatic or relapsed ULMS (MRULMS). Methods: This monocentric study included MRULMS pts with a physiological age < 65 y. CT consisted in doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/d d1d2 + mesna, cisplatin 75 mg/m² d3, + G-CSF; q 3 weeks. Results: Results in 38 pts with MRULMS were analyzed; median age was 51 (40-64), median cycles of CT was 5; 8 (21%) pts were treated for local relapse, 21 (55.3%) for metastatic disease and 9 (23.7%) for both. Metastatic sites were: lungs in 16 pts (42.1%), pelvis in 7 pts (18.4%), liver in 7 pts (18.4%), peritoneum in 6 pts (15.8%) and bone in 5 pts (13.2%); 14 pts (36.8%) had a multisite metastatic disease. Main grade 3-4 toxicities in 38 pts were neutropenia (74%), thrombopenia (60%), anemia (55%), fatigue (18%) and vomiting (13%). Febrile neutropenia was observed in 35% of pts and 1 patient died of septic shock after cycle 1. Thirty four pts were evaluable for response (4 pts had complete surgery at relapse) and 16 pts responded (4 CR + 12 PR) (ORR: 47%); 23.5% and 29.4% of the pts had respectively stable and progressive disease. For all pts (38) and evaluable pts (34), median PFS were 9.8 and 9.5 months and OS 27 and 25.3 months respectively. Conclusions: Despite toxicity observed, API is an effective treatment which compares favorably with other first line therapies for MRULMS pts.

Whether mCRC patients with other RAS mutations benefit from the addition of bevacizumab as first-line therapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 579-579
Author(s):  
Mingyi Zhou ◽  
Ping Yu ◽  
Kezuo Hou ◽  
Xiujuan Qu ◽  
Yunpeng Liu ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Large Sample Size ◽  
First Line ◽  
Exon 2 ◽  
Ras Mutations ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference ◽  
Ras Status ◽  
Kras Exon

579 Background: It is not clear whether Bevacizumab plus chemotherapy could improve the prognosis of mCRC patients with other RAS mutations beyond KRAS exon 2. Methods: The MEDLINE, EMBASE, Cochrane databases, and Clinical Trials databases were reviewed to September 2015. The data of patients with KRAS exon 2 mutations was only available in FIRE3 study. So we could not perform the meta-analysis by KRAS exon 2 mutations. The data of patients with other RAS mutations beyond KRAS exon 2 were available in PEAK and FIRE3 studies. Hazard ratio (HR) was used to analyze the progressive-free survival (PFS) and overall survival (OS). Relative risk (RR) was used to analyze overall response rate (ORR). Results: Patients with other RAS mutations beyond KRAS exon 2 benefited from the addition of Bevacizumab. Bevacizumab + chemotherapy significantly improved the PFS compared with anti-EGFR moAb + chemotherapy (HR: 1.82, CI: 1.20–2.77, P =.005). The addition of Bevacizumab tended to improve ORR, though there is no significant difference (RR: 0.83, CI: 0.58–1.18, P =.288). But the OS tended to be shorter in Bevacizumab + chemotherapy arm than anti-EGFR moAb + chemotherapy arm without significant difference (HR: 0.72, CI: 0.25–2.05, P =.534). Conclusions: Patients with other RAS mutations beyond KRAS exon 2 could choose Bevacizumab plus chemotherapy as first-line therapy. But there is still no adequate evidence to reject or support the predictive value of RAS status in the effect of the addition of Bevacizumab. Moreover, which is the better primary endpoint, PFS or OS? Which is the better consequence of strategy, anti-EGFR moAb followed by Bevacizumab or Bevacizumab followed by anti-EGFR moAb? RCTs with large sample size comparing the efficacy of anti-VEGF moAb + chemotherapy and chemotherapy alone by RAS status as the first-line therapy in mCRC patients are required in the future.

Overall survival analysis of the FOXFIRE prospective randomized studies of first-line selective internal radiotherapy (SIRT) in patients with liver metastases from colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3507-3507 ◽  
Author(s):  
Ricky A. Sharma ◽  
Harpreet Singh Wasan ◽  
Guy A. Van Hazel ◽  
Volker Heinemann ◽  
Navesh K. Sharma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Liver Metastases ◽  
Response Rate ◽  
Objective Response ◽  
Hepatic Metastases ◽  
First Line ◽  
Selective Internal Radiotherapy ◽  
Internal Radiotherapy ◽  
Randomized Studies

3507 Background: The FOXFIRE, SIRFLOX and FOXFIRE-Global (FF-SF-FFG) randomized studies evaluated the efficacy of combining first-line chemotherapy for metastatic colorectal cancer (mCRC) with selective internal radiotherapy (SIRT) using yttrium-90 resin microspheres in patients with liver metastases. The studies were designed for prospective, combined analysis of overall survival (OS). Methods: FF-SF-FFG randomized (1:1) chemotherapy-naïve mCRC patients (performance status 0/1) with liver metastases not suitable for curative resection/ablation. Arm A was oxaliplatin-based chemotherapy (mFOLFOX6/ OxMdG) ± investigator-chosen biologically targeted agent. Arm B was the same systemic therapy (oxaliplatin dose modification) + single treatment SIRT with cycle 1/2 of chemotherapy. Primary tumor in situ and/or limited extra-hepatic metastases were permitted. Minimum sample size was 1075 patients (HR 0.8, 80% power, two-sided 5% significance). Secondary outcomes included PFS, liver-specific PFS and response rate. Apart from safety, outcomes were analysed on intention-to-treat population using meta-analytic methods of pooled individual patient data. Results: Between 2006 and 2014, 1103 patients were randomized in 14 countries. Median age was 63 years (range 23-89); median follow-up 43.3 months. There were 844 deaths. There was no difference in OS (HR 1.04; 95% CI 0.90-1.19, p= 0.609) or PFS (HR 0.90, CI 0.79-1.02, p= 0.108) between Arms. Objective response rate ( p= 0.001) and liver-specific progression (HR 0.51, CI 0.43-0.62, p< 0.001) were significantly more favorable in Arm B. Patients in Arm B had higher risk of non-liver progression as first event (HR 1.98, CI 1.53-2.58, p< 0.001). Grade 3-5 adverse events were more common in Arm B (74.0%) than A (66.5%), p= 0.009. In health status questionnaires, EQ-5D utility scores were not significantly different between Arms at 6, 12 or 24 months. Conclusion: Despite higher response rates and improved liver-specific PFS, the addition of SIRT to first-line oxaliplatin-fluorouracil chemotherapy for patients with liver-only and liver-dominant mCRC did not improve OS or PFS. Clinical trial information: 83867919.

Retrospective analysis of the effects of systemic chemotherapy to the ovarian metastases from colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 731-731 ◽  
Author(s):  
Katsutoshi Sekine ◽  
Tetsuya Hamaguchi ◽  
Hirokazu Shoji ◽  
Shoko Nakamura ◽  
Takahiro Miyamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Surgical Resection ◽  
Cytoreductive Surgery ◽  
Systemic Chemotherapy ◽  
Palliative Chemotherapy ◽  
Objective Response ◽  
First Line ◽  
Ovarian Metastases ◽  
Third Line ◽  
Metastatic Sites

731 Background: Ovarian metastases from colorectal cancers are relatively rare. Since most ovarian metastases are also associated with other metastatic sites, the prognosis is reported to be poor. It is not fully understood whether the response to systemic chemotherapy of ovarian metastases differs from that to other metastatic sites. Methods: We retrospectively reviewed the clinical data of patients with ovarian metastases from colorectal cancer treated at our hospital between January 2006 and December 2015. Results: Among the 635 female patients with relapsed or metastatic colorectal cancer, 57 (9.0%) had ovarian metastases before the first-line treatment; 37 patients received palliative chemotherapy, and 20 patients were initially treated by surgical resection. In addition, 38 cases of ovarian metastases developed after the initiation of first-line chemotherapy. Overall, 95 patients (15.0%) with ovarian metastases were treated during this period. The objective response rate for systemic chemotherapy of ovarian metastases was lower than that for other metastatic sites (22.9 % vs 60.9 % for first-line, 3.4 % vs 13.6 % for second-line, 11.1 % vs 26.6 % for third-line, and 0% vs 18.2 % for fourth-line, respectively). After the initiation of chemotherapy, surgical resection of ovarian metastases was positively associated with a longer overall survival (26.8 months for cytoreductive surgery and 17.0 months for only systemic chemotherapy, p < 0.001), especially when the other metastatic sites had not progressed after chemotherapy. Conclusions: Ovarian metastases are less responsive to systemic chemotherapy compared to the extra-ovarian metastases. Our data also suggest that multi-disciplinary treatment strategy including systemic chemotherapy and cytoreductive surgery might improve the prognosis of ovarian metastases.

Withholding anti-EGFR, the impact on outcome in RAS wild-type metastatic colorectal tumors (WAIT or ACT trial).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 626-626
Author(s):  
Lola-Jade Palmieri ◽  
Laurent Mineur ◽  
David Tougeron ◽  
Benoit Rousseau ◽  
Victoire Granger ◽  
...  
Keyword(s):  
Growth Factor ◽  
Propensity Score ◽  
Cohort Analysis ◽  
Wild Type ◽  
First Line ◽  
Anti Vegf ◽  
Ras Status ◽  
Metastatic Sites ◽  
The Impact ◽  
Doublet Chemotherapy

626 Background: First line of RAS wild-type (WT) unresectable metastatic colorectal cancer (mCRC) can be doublet chemotherapy with an anti-VEGF (Vascular Endothelial Growth Factor), or an anti-EGFR (Epidermal Growth Factor Receptor). Waiting for RAS status, many oncologists initiate chemotherapy and add the anti-EGFR secondly. The objective was to compare the delayed introduction of the anti-EGFR to the immediate introduction of the anti-VEGF in first-line treatment of RAS WT mCRC. Methods: This was a retrospective cohort analysis from 2013 to 2016, multicentric with 28 health care centers. We included patients with RAS WT unresectable mCRC treated between 2013 and 2016 by a doublet chemotherapy with the anti-VEGF introduced immediately or with the anti-EGFR introduced at C2 or C3. Progression free survival (PFS), overall survival (OS) and response rate (RR) for the two cohorts were compared. Hazard ratios (HR) with 95% confidence interval (95%CI) were estimated with cox regression models weighted on propensity score to deal with potential confounders. Results: A total of 262 patients were included, 129 in the immediate anti-VEGF group and 133 in the delayed anti-EGFR group. Median follow-up was 37.9 months. Ninety-two patients had the anti-EGFR introduced at C2, 40 at C3. The median delay of RAS analysis was 19 days (q1-q3: 13-26). Patients treated with anti-VEGFs were more likely men (68% versus 56%), with more metastatic sites ( > 2 sites: 15% versus 9%). A propensity score including the number of metastatic sites and a possible previous treatment was built. Delayed anti-EGFRs were associated with longer PFS compared to immediate anti-VEGFs: 13.8 versus 11.0 months, p = 0.0244. After weighting, delayed anti-EGFRs were still associated with better PFS: HR 0.74, 95%CI [0.61 – 0.90], p = 0.0024. OS was not different between the two arms (30.5 for anti-VEGF versus 29.9 months, p = 0.3934), even after weighting (HR 0.86, 95%CI [0.69 – 1.08], p = 0.2024). There was a better RR with delayed anti-EGFRs: 66.7% versus 45.6%, p = 0.0007. Conclusions: Our findings suggest that, while waiting for RAS status, the delayed introduction of the anti-EGFR is a valid option, compared to the immediate introduction of the anti-VEGF.

Capecitabine maintenance therapy after docetaxel/capecitabine combination chemotherapy in patients with metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12018-e12018
Author(s):  
Pinar Gursoy ◽  
Zeki Gokhan Surmeli ◽  
Burcu Cakar ◽  
Cagatay Arslan ◽  
Baha Zengel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Maintenance Therapy ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Complete Response ◽  
Response To Treatment ◽  
Grade 3 ◽  
Metastatic Sites

e12018 Background: Addition of capecitabine to docetaxel improves survival outcomes compared with single agent docetaxel in metastatic breast cancer (MBC). In this study we analyzed efficacy of maintenance therapy with single agent capecitabine after six cycles of docetaxel/capecitabine chemotherapy in MBC patients. Methods: Patients with metastatic HER2 negative breast cancer were included. Six cycles of docetaxel (75mg/m2 q3wk) / capecitabine (1650mg/m2/day on days 1 to 14) followed by capecitabine (2000 mg/m2/day on days 1 to 14) were administered. Demographic features, progression free (PFS) and overall survival (OS) and response to treatment were recorded. Results: Fifty-four patients were included. Thirty-five patients (65%) were postmenopausal, and 40 (74%) were ER/PR positive. Median age was 53 (range 28 – 70). Number of metastatic sites was one in 23 patients, two in 21, three or more in 10 patients. Most common metastatic sites were bone (67%), lymph nodes (33%), lungs (30%), liver (13%); 13 patients (24%) had bone only disease. Forty-four (81.5%) patients received treatment in first-line, 10 (18.5%) received in second line setting. Median number of cycles applied (including docetaxel/capecitabine combination) was 9 (range 2 – 31, total 576). Median PFS was 9 months (10.4 for hormone receptor positive, 7.3 for negative patients) and median OS was 28 months. Objective response was assessable in 38 patients. Overall response rate (partial + complete response) was 42.6% (95% CI 29.6 – 55.6) with 1 complete response. Toxicities were evaluated in 41 patients; grade 3/4 neutropenia was observed in 10% and grade 3/4 hand-foot syndrome was observed in 24% of patients. Dose reduction was performed in capecitabine in 37%, and in docetaxel in 20% of patients. Conclusions: Maintenance with single agent capecitabine therapy after six cycles of docetaxel/capecitabine chemotherapy is an effective and tolerable treatment option for HER2 negative MBC patients.

Effects of baseline lactate dehydrogenase (LDH), interferon gamma (IFN-g) expression, and tumor mutational burden (TMB) on treatment response to first-line atezolizumab (A) + vemurafenib (V) and cobimetinib (C) in BRAFV600 mutation–positive advanced melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9523-9523
Author(s):  
Caroline Robert ◽  
Karl D. Lewis ◽  
Paolo Antonio Ascierto ◽  
Rodrigo Ramella Munhoz ◽  
Gabriella Liszkay ◽  
...  
Keyword(s):  
Group Performance ◽  
Performance Status ◽  
Recursive Partitioning ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Complete Response ◽  
Advanced Melanoma ◽  
First Line ◽  
L1 Data ◽  
Metastatic Sites

9523 Background: The phase 3 IMspire150 study showed that first-line A+V+C improved investigator-assessed PFS vs placebo (P)+V+C in BRAFV600E/K mutation–positive advanced melanoma (hazard ratio 0.78; P=.0249). Prior biomarker analyses showed that IFN-g or TMB > 10 mut/Mb were associated with greater PFS benefits with A+V+C (Lewis et al. J ImmunoTher Cancer 2020;8:A188-A189). We further evaluated the association of these biomarkers with outcomes. Methods: Exploratory recursive partitioning analysis (RPA) was used to model associations between PFS and age ( < 65 vs ≥65 y), Eastern Cooperative Oncology Group performance status (0 vs 1), liver metastases (yes vs no), metastatic sites (≤3 vs > 3), sum of longest tumor diameters ( < 44 mm vs ≥44 mm), baseline LDH (normal [n] vs elevated [e]), TMB ( < 10 vs ≥10 mut/Mb), PD-L1 (negative vs positive), and IFN-g (high [h; > Quartile 3; Q3] vs intermediate [ > Q1 and ≤Q3] vs low [≤Q1]). Time-to-event analyses were summarized using Kaplan-Meier estimates. Results: The RPA analysis included 208/256 (81.3%) patients (pts) from the A+V+C arm of IMspire150 for whom LDH, TMB, IFN-g, and PD-L1 data were available. RPA showed that LDH was associated with PFS. In pts treated with A+V+C and n-LDH, h-IFN-g signature was associated with longer PFS and higher rates of objective response (OR) and complete response (CR) vs low/intermediate (l/i) IFN-g (2-y PFS: 59% vs 38%; ORR: 77% vs 69%; CR: 38% vs 15%, respectively); TMB ≥10 mut/Mb was associated with more favorable outcomes in pts with e-LDH (Table). In contrast, neither IFN-g nor TMB discriminated PFS outcomes in n-LDH or e-LDH pt subgroups receiving P+V+C. Pts with e-LDH and TMB < 10 mut/Mb had poor PFS outcomes, with 2-y PFS rates of 9% and 3% and lower rates of OR (51% and 62%) and CR (5% and 9%) in the A+V+C and P+V+C arms, respectively. Similar trends were observed for duration of response (DOR), and for the subset of pts with BRAFV600E mutation–positive melanoma. A+V+C improved PFS vs P+V+C across all subgroups with the exception of e-LDH and TMB < 10. Conclusions: IFN-g and TMB discriminated PFS benefit in pts receiving A+V+C but not for those receiving P+V+C. Durable responses were observed for pts treated with A+V+C in the n-LDH + h-IFNg subgroups.[Table: see text]

scholarly journals Hyperprogressive Disease Caused by PD-1 Inhibitors for the Treatment of Pan-Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Shiyun Chen ◽  
Miaomiao Gou ◽  
Huan Yan ◽  
Mengjiao Fan ◽  
Yuting Pan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Tumor Markers ◽  
Malignant Tumors ◽  
Hepatic Metastases ◽  
Lactate Dehydrogenase Level ◽  
Tumor Growth Rate ◽  
Hyperprogressive Disease ◽  
Metastatic Sites ◽  
Pan Cancer

Background. Nowadays, PD-1/PD-L1 inhibitors are widely used to treat various malignant tumors. However, during the immunotherapy in a few patients, a flare-up of tumor growth occurred. This new pattern of progression is called hyperprogressive disease (HPD). Patients and Methods. The retrospective study included 377 patients with various malignant tumors treated with PD-1 inhibitors (nivolumab or pembrolizumab) in the Chinese PLA General Hospital from January 2015 to January 2019. Clinicopathologic variables, tumor growth rate (TGR), and treatment outcomes were analyzed in patients with pan-cancer treated with PD-1 inhibitors. HPD was defined as the difference of TGR before and during immunotherapy exceeding 50%. Results. In 38 of 377 patients (10.08%), HPD occurred after treatment with PD-1 inhibitors. Patients with HPD had lower overall survival (OS) than those without HPD (median OS, 3.6months (95% CI, 3.0–4.2) vs. 7.3 months (95% CI, 5.9–8.7); P < 0.01 ). Factors related to HPD include more than 2 metastatic sites, ECOG performance status ≥ 2 , hepatic metastases, and lactate dehydrogenase level greater than normal upper limit. KRAS status was significantly associated with HPD in patients with colorectal cancer. In the exploratory predictors’ analysis, the rapid increase of characteristic tumor markers (such as CEA in colorectal cancer, CA199 in pancreatic cancer and cholangiocarcinoma) within one month was found to be associated with the occurrence of HPD. Conclusions. HPD was developed with different rates in a variety of malignant tumor patients treated with PD-1 inhibitors and related to some clinicopathological features and poor prognosis. Tumor markers, especially CA199, might be served as early predictors of HPD.

Preliminary results of second-line chemotherapy with vinorelbine and gemcitabine after docetaxel and carboplatin failure in advanced non small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17130-17130
Author(s):  
J. Abou Yared ◽  
G. Chahine ◽  
J. Kattan ◽  
F. Farhat ◽  
W. Moukadem ◽  
...  
Keyword(s):  
Objective Response ◽  
Response Duration ◽  
Response To Therapy ◽  
First Line ◽  
Preliminary Results ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Line Chemotherapy

17130 Background: To evaluate the efficacy and safety of a doublet platinum-free therapy based on Vinorelbine and Gemcitabine in the salvage treatment of patients with advanced NSCLC, previously treated with Carboplatin and Docetaxel. Methods: We conducted a phase II study with the combination of vinorelbine 30 mg/m2 and gemcitabine 1000 mg/m2 d1 d8 / 3w. Eligible were patients with histologically proven advanced or metastatic NSCLC who were refractory or progressed after first-line chemotherapy combining Docetaxel and Carboplatin. Results of this first-line therapy were already reported (Proc. Am. Soc. Clin. Oncol. 2005, abstr 7330). Patients must have measurable disease, PS ≤ 2, life-expectancy ≥ 3 months, adequate hematologic, liver and renal functions. Response to therapy was evaluated according to RECIST guidelines. Toxicities were assessed according to the national cancer institute (NCI) common toxicity criteria 3.0. Results: From August 2004 to September 2005, 28 patients were enrolled. Median age was 63 years (range, 44 to 77) with 18 males and 10 females. A total of 109 cycles were delivered with a median of 4 cycles per patient (range, 1 to 9). Mean metastatic sites were lymph nodes in 9 pts, liver in 6 pts and pleura in 5 pts. 26 patients were evaluable for response (1 patient too early and 1 pt lost of follow-up). 6 patients responded partially (23%), one of them was initially resistant to the first-line therapy. 11 patients had stable disease (42%). Mean objective response duration was 7 months (range, 5 to 10+). Main toxicities (grade 3/4) were: anemia in 4 patients, neutropenia in 7 patients, leucopenia in 8 patients and lymphopenia in 4 patients. Neutropenic fever was encountered in only one patient. Non-hematological toxicities grade 3/4 were universally absent. No dose reduction or treatment delay related to toxicity was necessary. Conclusion: The study is still ongoing and more patients are expected to define time to progression and survival. However, these preliminary results were encouraging with low toxicity profile. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document