Prognostic impact of changes in circulating tumor cells (CTC) in metastatic breast cancer (MBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11012-11012
Author(s):  
Markus Wallwiener ◽  
Andreas D. Hartkopf ◽  
Sabine Riethdorf ◽  
Martin Sprick ◽  
Christoph Wolfram Domschke ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Progressive Disease ◽  
Tumor Response ◽  
Metastatic Breast ◽  
Prognostic Impact ◽  
Best Response ◽  
Line Of Therapy ◽  
Age Range ◽  
Clinical Trial Information

11012 Background: To prospectively assess the prognostic value of CTC counts at baseline and after one cycle of therapy and their kinetics for response, progression-free (PFS), and overall survival (OS) in MBC. Methods: MBC patients underwent CTC enumeration (CellSearch, Veridex) at baseline (CTCBL), after one cycle of a new line of therapy (CTC1C), and at progression (CTCPD). CTC status was classified as negative (neg (−)) or positive (pos (+)) for <5 and ≥5 CTC/7.5 ml peripheral blood, respectively. CTC kinetics (CTCKIN) from CTCBL to CTC1C were classified as favorable if CTCs remained neg (neg>neg) or became neg (pos>neg), or as unfavorable (neg>pos or pos>pos). Tumor response was assessed every 2–3 months using RECIST criteria. CTC status and kinetics were associated with outcome using log-rank and Fisher’s exact tests. Results: Of 326 patients enrolled (median age (range) at first diagnosis: 50 (23–81) years), 115/326 (35%) were CTCBL+, 51/162 (31%) were CTC1C+, and 39/108 (36%) were CTCPD+. Median follow-up was 15.9 months (mos). Median PFS and OS were significantly reduced in CTCBL+ compared to CTCBL− patients (PFS, 4.3 vs. 7.1 mos, p = .019; OS, 15.0 mos vs. not reached (nr), p <.001) and for CTC1C+ compared to CTC1C− patients (p <.001 for PFS and OS). CTCKIN were predictive of progressive disease as best response (neg>neg, 33%; pos>neg, 38%; pos>pos, 60%; neg>pos, 75%; p = .040). PFS and OS for patients with unfavorable CTCKIN were significantly shorter than for favorable CTCKIN (PFS, 3.7 vs. 6.8 mos, p <.001; OS, 7.8 mos vs. nr, p <.001). Conclusions: CTC at baseline, CTC after one cycle and CTC kinetics are highly predictive of outcome in MBC. Serial CTC enumeration could serve as a useful adjunct to standard diagnostic tests in tailoring therapy. Further details of CTCPD will be presented at the meeting. Clinical trial information: S-295/2009.

Single agent ONC201 in adult recurrent H3 K27M-mutant glioma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3005-3005
Author(s):  
Isabel Arrillaga ◽  
Sylvia Kurz ◽  
Ashley Sumrall ◽  
Nicholas A. Butowski ◽  
Rebecca A. Harrison ◽  
...  
Keyword(s):  
Stable Disease ◽  
Poor Prognosis ◽  
Progressive Disease ◽  
Tumor Regression ◽  
Single Agent ◽  
Complete Regression ◽  
Compassionate Use ◽  
Best Response ◽  
Clinical Trial Information

3005 Background: H3 K27M-mutant glioma is associated with a poor prognosis and there is no effective therapy following radiation. We report the clinical experience with single agent ONC201, the first small molecule DRD2 antagonist in oncology, in adults with recurrent H3 K27M-mutant glioma. Methods: Twenty-nine adult patients with recurrent H3 K27M-mutant glioma have been treated with single agent ONC201 as of January 20, 2019: 19 patients on NCT03295396; 8 patients on NCT02525692; 2 patients on compassionate use protocols under the Sponsor’s IND. Median age was 57 years old (range: 17-74), median prior lines of therapy was 2 (range: 1-4) and all patients received prior radiation (median 8.5 months from radiation completion to ONC201 initiation). ONC201 was orally administered at 625 mg weekly, except for one patient dosed once every 3 weeks. Results: As of February 5, 2019, 13 of 29 patients remain on-trial within median follow up of 6.5 months (range: 0.6-33.6), 8 patients are alive but off-trial with median follow up of 2.4 months (range: 0.2-9), and 8 patients have expired. Nine of 29 patients (31%) remain progression-free on ONC201 with a median follow up of 6.5 months (range 0.6-33.6). No dose-limiting toxicities or treatment discontinuations due to toxicity occurred. Three patients have experienced durable partial responses by RANO (4.3-28.5 months). In addition, one patient experienced complete regression that continues for > 14 months of all < 1 cm tumor lesions that are not measurable by RANO. Furthermore, 10 patients had a best response of stable disease by RANO, 12 patients experienced progressive disease, and 3 patients are not yet evaluable. Among the patients with a best response of stable disease by RANO, one patient had > 50% tumor regression in the basal ganglia that did not qualify as a partial response by RANO due to a new lesion on a confirmatory scan. Another patient with stable disease by RANO has had 37% tumor regression so far in the brainstem and remains on-treatment for 6 months. All tumor regressions remain durable to date and some were associated with improvements in disease-associated neurological symptoms. Conclusions: Single agent ONC201 is well tolerated and clinically active in adult recurrent H3 K27M-mutant glioma patients. Clinical trial information: NCT03295396; NCT02525692.

Phase Ib/II study of pembrolizumab with lanreotide depot for advanced, progressive gastroenteropancreatic neuroendocrine tumors (PLANET).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 369-369
Author(s):  
Michael Morse ◽  
Daniel M. Halperin ◽  
Hope Elizabeth Uronis ◽  
David S. Hsu ◽  
Herbert Hurwitz ◽  
...  
Keyword(s):  
External Beam Radiotherapy ◽  
Locoregional Therapy ◽  
Somatostatin Analogue ◽  
Antitumor Effects ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Best Response ◽  
Secondary Endpoints ◽  
Clinical Trial Information ◽  
Experienced Treatment

369 Background: Pembrolizumab has antitumor activity in a subset of GEP-NETs patients. We hypothesized that the lanreotide, by its antitumor effects and reduction of serotonin, a modulator of immunity, would synergize with pembrolizumab in low/intermediate grade GEPNETs. Methods: GEP-NETs patients who had progressed on a prior somatostatin analogue received lanreotide 90mg sq and pembrolizumab 200mg IV every 3 weeks until progressive disease or intolerable toxicity. The primary endpoint was ORR at any time on study and secondary endpoints were PFS and OS. Results: 22 patients were treated (F/M 10/12; Caucasian/AA/other 10/7/5; GI/pancreatic 14/8; median Ki67 5%, median time since diagnosis 5.3 yrs (IQR 2.3-7.9 yrs)). Prior octreotide LAR/lanreotide/both was administered to 20/1/1. Patients had a median of 2 prior systemic therapies (range 1-9) and six had prior locoregional therapy and 3 external beam radiotherapy. Of the 12 tumors analyzed thus far, 4 had detectable PD-L1 expression and 11 had detectable TILs. A median of 6 pembrolizumab doses (range 2-15) and 7 lanreotide doses (range 2-15) were administered. Six patients experienced treatment related SAEs (abdominal pain, pneumonitis, colitis, and hyperglycemia, all related to the pembrolizumab). Selected treatment related adverse events included: Hypothyroidism 23%, colitis 9%, hyperglycemia 14%, and pneumonitis 5%. Best response by RECIST 1.1 was SD/PD/Not available:39/52/9% and by irRECIST was 43/48/9%. Median PFS was 5.4 months (95% CI 1.7-8.3 mo). The median overall survival at a median follow-up of 15 months was not reached. Peripheral blood immunologic correlates will be reported subsequently. Conclusions: In a population of GEP-NET patients, progressing on a median of 2 prior therapies, including prior somatostatin analogue therapy, a minority of whom had PD-L1 expressing tumors, the combination of lanreotide and pembrolizumab produced stable disease in approximately 40% of patients. No new safety signals were identified. Clinical trial information: NCT03043664.

CLO19-026: Determining the Treatment Decision of Tumors With Mixed Response

2019 ◽  
Vol 17 (3.5) ◽  
pp. CLO19-026
Author(s):  
Candice Baldeo ◽  
Tasneem Kaleem ◽  
Ricardo Paz-Fumagalli ◽  
John Copland ◽  
Michael Menefee
Keyword(s):  
Tumor Response ◽  
Treatment Decision ◽  
Clinical Decision ◽  
Hematologic Malignancies ◽  
Current Treatment ◽  
Response To Treatment ◽  
Mixed Response ◽  
Line Of Therapy ◽  
Additional Agent

Introduction: Individuals receiving systemic anticancer therapies for advanced solid tumors routinely undergo imaging studies to assess the efficacy of the treatment. Mixed response (MR) to cancer therapy is a common but poorly described phenomenon. There is a paucity of data regarding both the incidence and possible mechanisms of this clinical quandary. Potential etiologies include tumor heterogeneity, differences in tumor microenvironment, and discrepancies in drug delivery to different tumor deposits. It is also possible that MR simply reflects differences in the rate of resistance emerging. MR represents a therapeutic dilemma for the clinician. Methods: Mixed tumor response was defined as: One tumor decreasing in size; one tumor increasing in size (classified as RECIST response/progressions), One tumor stable; another tumor progressing, One tumor stable; another tumor responding, New tumor; another tumor responding or remaining stable. Between 2015 and 2017, 120 restaging CT scans were reviewed of patients who had received at least 1 line of therapy for advanced cancer diagnosis which showed MR; hematologic malignancies were excluded. Charts were reviewed to determine the clinical decision that was made at the time of the MR. Results: A total of 120 scans with MR were reviewed from various solid tumor diagnoses. 38 scans were excluded due to loss of follow-up or death. Of the remaining 82 scans, therapy was switched in 30, the same therapy was continued in 50, and an additional agent was added to the current treatment in 2 cases (Table). Of the patients in which treatment was switched, 20% (6/30) showed response to treatment on the following scan. Of the cases that were kept on current treatment, none showed response on the following restaging scan which was done 6–8 weeks later. There were 4 (10%) deaths prior to the next scan in the group that had treatment switched and similarly 5 deaths (10%) prior to the next scan in the group in which treatment remained the same. Conclusion: MR is associated with a poor prognosis, irrespective of treatment decisions. These data are retrospective and our sample size is small, so definitive conclusions cannot be drawn. However, changing therapy when a MR is observed may be of benefit to some patients. A prospective evaluation to more accurately describe and understand the MR phenomenon is warranted.

Fludarabine Plus Cyclophosphamide and Rituximab In Waldenström's Macroglobulinemia: Results In 55 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1757-1757
Author(s):  
Véronique Leblond ◽  
Laetitia Compain ◽  
Vincent Levy ◽  
Jérôme Tamburini ◽  
Alain Delmer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Progressive Disease ◽  
Response Rate ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Best Response ◽  
Previously Treated ◽  
Delayed Responses

Abstract Abstract 1757 Treatment of Waldenström's Macroglobulinemia relies on alkylator agents, nucleoside analogs and/or monoclonal antibody based therapies. We showed previously that combination of fludarabine and cyclophosphamide yields a 78% response rate (RR). We performed a retrospective study in 55 WM patients (pts) treated with RFC regimen in 10 French centers. The median age was 65 years (range: 34–79), the median IgM level measured by electrophoresis was 27.3 g/L (range: 6.5–64), the median haemoglobin level was 9.7g/dl (range: 3.7–14), the median platelet count was 174 × 109/L (range: 22–500), the median beta 2 microglobulin level was 3.4 mg/l (range: 1.7–9). In all, 40/55 pts had previously been treated with a median of 2 lines of therapy (range: 1–4), including 24 patients with relapsed disease and 16 patients with refractory disease. RFC regimen was given every 4 weeks and consisted in: Rituximab 375 mg/m2 IV Day 1, Fludarabine 40 mg/m2 per os Day 1 to Day 3, Cyclophosphamide 250 mg/m2 per os Day 1 to Day 3. 55 pts received the first cycle of RFC, and 52 received two or more cycles (median of 4 cycles, range 2–6). Main toxicity was hematological. No toxic death was observed.Response was assessed 3 months after the last RFC cycle according to response criteria agreed by the 3rd International Workshop on WM (Kimby, 2006), but delayed responses with improvement of the response occurring more than 3 months after treatment discontinuation were observed in 15 patients. The best response was evaluated in 51 pts (3 early discontinuation treatments, one progressive disease), including 26 partial responses (PR), 5 minor responses (MR), and 2 stable diseases (SD). Of note 18 very good PR/ near RC (VGPR) were observed (> 90% decrease in M-protein) . The overall response rate was 89%. Long lasting cytopenia was observed in 10 patients. In the untreated group one pt in failure had a Burkitt-like lymphoma, the other 14 pts are alive in response. In the previously treated group, 6 pts relapsed, one developed a large B-cell lymphoma. Three ASCT and 4 allogeneic SCT were performed in six patients. With a median follow-up time of 28 months, median time to treatment failure (TTF) was not reached, even in previously treated patients. There was not significant difference in the TTF duration in patients in VGPR compared with those in PR + MR.The median progression free survival time was not reached. Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) was observed in two heavily treated patients and 3 pts had a secondary solid cancer. In all, 48 pts are alive, 7 patients died (4 from progressive disease, 2 from secondary cancer, and 1 from Burkitt-like transformation). Conclusion: RFC combination even in heavily treated patients with poor prognostic factors gives a very high response rate (89%) with 33% of patients achieving at least a very good partial response with acceptable toxicity. The toxicity on the hematopoietic stem cell reservoir is a major concern. This combination could be offered to relapsed/refractory patients. In first line, the choice of this combination must be discuss, increased incidence of MDS/ AML after purine analogs, and impairment of stem cell mobilization having previously been reported by us and others. Because frequent delayed responses, a long follow-up with periodic electrophoresis is needed to assess the best response after RFC. Disclosures: Leblond: ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MUNDIPHARMA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GENZYME: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees; JANSSEN: Membership on an entity's Board of Directors or advisory committees. Tournilhac:MUNDIPHARMA: Membership on an entity's Board of Directors or advisory committees; GENZYME: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees. Choquet:ROCHE : Consultancy.

The Long PD-1 Receptor Binding Kinetics of Nivolumab May Increase Efficacy of Subsequent Therapy in Relapsed and Refractory Multiple Myeloma Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3057-3057 ◽  
Author(s):  
Samuel A. Funt ◽  
David B. Page ◽  
Deepika Cattry ◽  
Nikoletta Lendvai ◽  
Hani Hassoun ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Receptor Binding ◽  
Research Funding ◽  
Progressive Disease ◽  
Binding Kinetics ◽  
Open Label ◽  
Open Label Study ◽  
Refractory Multiple Myeloma ◽  
Best Response ◽  
Line Of Therapy

Abstract Introduction: Programmed cell death-1 (PD-1) signaling suppresses the antigen driven activation of T cells upon interaction with its ligands PD-L1 and PD-L2. The PD-1/PD-L1 axis is thought to mediate the resistance of multiple myeloma to conventional therapy (Tamura 2013; Paiva 2015). Nivolumab, a fully human IgG4 monoclonal PD-1 receptor-blocking antibody, has shown clinical activity in a variety of tumor types. Nivolumab has demonstrated a prolonged receptor binding kinetic lasting >100 days that may lead to an efficacy or toxicity signal in the post-treatment period. We therefore evaluated the response of patients with relapsed or refractory multiple myeloma to additional myeloma therapy received within 3 months of the end of nivolumab administration. Methods: The preliminary results of an open-label study that treated patients with relapsed or refractory multiple myeloma using a dose escalation design (1 mg/kg and 3 mg/kg) of nivolumab administered every 2 weeks have been reported previously (NCT01592370, Lesokhin et al., ASH 2014). Here we will report responses and safety data using standard criteria to the next line of therapy received immediately after nivolumab. Results: 8 patients with multiple myeloma from the original open label study were treated at Memorial Sloan Kettering Cancer Center. The disease characteristics and efficacy results are shown in the table. 1 of 8 patients (12.5%) experienced progression while on therapy manifested by development of an isolated plasmacytoma. The patient received radiation and then resumed and completed 97 weeks of therapy with nivolumab. He is currently off therapy without any evidence of disease at 48 weeks after cessation of nivolumab. 3 of 8 patients (37.5%) achieved a partial response to the next line of treatment after nivolumab. 2 of 8 patients (25%) who were exposed and refractory to immunomodulatory drugs (IMiDs) received single-agent, low-dose lenalidomide as the next line of therapy and achieved stable disease lasting approximately 100 days after cessation of nivolumab followed by disease progression. 1 of 8 patients (12.5%) experienced progressive disease despite the next line of therapy, and 1 of 8 patients (12.5%) received an experimental treatment as the next line of therapy and was therefore not evaluable. No new drug-related adverse events occurred in the 3 months after completing treatment with nivolumab. Overall, 6 out of 8 patients derived clinical benefit from post-nivolumab therapy, an unusually high response rate for this population. Conclusions: In a small cohort of patients with relapsed and refractory multiple myeloma, evaluation of response kinetics after cessation of nivolumab supports the notion that long PD-1 receptor binding kinetics may increase the efficacy of subsequent therapy without added toxicity. Larger studies are needed to confirm and expand our findings. Table. Patient Characteristics and Efficacy Age Sex ISS Cytogenetics Prior Lines ASCT IMiD E IMiD R Prot E Prot R Best Response to Nivolumab Next Line of Standard Therapy Best Response to Next Line 52 M 1 S 3 Y Y Y Y Y SD Carfilzomib, Cyclophosphamide, Dexamethasone PR 32 M 1 S 3 Y Y Y Y Y SD None* N/A 80 F 1 S 1 N Y N N N SD Lenalidomide PR 52 F 1 I 3 Y Y Y Y N SD Lenalidomide SD 62 M 1 H 1 Y Y N Y N PD Cyclophosphamide, Bortezomib, Dexamethasone PR 58 M 2 S 5 Y Y Y Y Y PD Lenalidomide SD 57 F 1 S 3 Y Y N Y Y PD None^ N/A 59 F 1 S 3 Y Y Y Y Y PD Lenalidomide, Bortezomib, Dexamethasone PD ISS=international staging system; S=standard cytogenetics; I=intermediate cytogenetics; H=high risk cytogenetics; ASCT=autologous stem cell transplant; IMiD E=IMiD exposed; IMiD R=IMiD refractory; Prot E=proteosome exposed; Prot R=proteosome refractory; PD=progressive disease; SD=stable disease; PR=partial response *Patient completed 97 weeks of nivolumab and continues untreated without any evidence of disease at 48 weeks after cessation of therapy ^Patient received treatment on an experimental protocol Disclosures Funt: Kite Pharma: Equity Ownership. Off Label Use: Nivolumab is FDA approved for use in patients with metastatic melanoma but not in patients with multiple myeloma. . Page:Celgene: Consultancy. Landgren:Bristol-Myers Squibb: Honoraria; Celgene: Consultancy; BMJ Publishing: Consultancy; Bristol-Myers Squibb: Consultancy; BMJ Publishing: Honoraria; Medscape: Consultancy; Medscape: Honoraria; Celgene: Honoraria; International Myeloma Foundation: Research Funding; Onyx: Honoraria; Onyx: Research Funding; Onyx: Consultancy. Borrello:Celgene: Research Funding. Lesokhin:Bristol Myers Squibb: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Aduro: Consultancy; Genentech: Research Funding; Efranat: Consultancy.

Comparison of progression-free survival (PFS) and tumor response as endpoints for predicting overall survival (OS) in untreated extensive-stage small cell lung cancer (ED-SCLC): Findings based on North Central Cancer Treatment Group (NCCTG) trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8085-8085
Author(s):  
N. R. Foster ◽  
Y. Qi ◽  
J. E. Krook ◽  
J. W. Kugler ◽  
S. A. Kuross ◽  
...  
Keyword(s):  
Tumor Response ◽  
Logistic Models ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Prognostic Impact ◽  
Cox Models ◽  
Landmark Analysis ◽  
Best Response ◽  
Primary Endpoints ◽  
Extensive Stage

8085 Background: Historically, tumor response has been the primary endpoint in phase II (P2) trials in ED-SCLC. We investigated the suitability of alternate PFS based endpoints to predict OS as early evidence of efficacy in the P2 setting. Methods: Individual patient (pt) data from 942 pts from 11 previously untreated ED-SCLC P2 and phase III (P3) platinum- or paclitaxel-based treatment trials were pooled. Best response (BR), response confirmed (RC), objective status at 16 weeks (RR16), and PFS rate at 5 and 6 months were considered. Percent agreement (PA) and kappa (k) for PFS5, PFS6, BR, RC, and RR16 with OS at 12 months (OS12) was calculated on a per-pt basis and predictive utility was assessed using the area under the receiver operating characteristic (A- ROC) curve in logistic models. Cox models were used to assess the prognostic impact of the endpoints on subsequent survival, using landmark analysis. Results: The median OS and PFS were 9.6 m and 5.5 m, respectively. PFS5 and PFS6 had the highest PA, k, and A-ROC values, and were predictive of subsequent survival in the landmark analysis (p <0.0001; c-statistics ≥ 0.60). While RR16 and BR were significantly associated with subsequent survival (p<0.0001, c-statistics of 0.61 and 0.57, respectively) the PA, k, and A-ROC values were lower. Conclusions: PFS rate at 5 and 6 months is more predictive of 12-month OS and subsequent survival than tumor response in untreated ED-SCLC. PFS based endpoints should be routinely used as primary endpoints in P2 trials within ED-SCLC. [Table: see text] No significant financial relationships to disclose.

Cetuximab and chemotherapy in the treatment of patients with initially “nonresectable” colorectal (CRC) liver metastases: Long-term follow-up of the CELIM trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3538-3538 ◽  
Author(s):  
Gunnar Folprecht ◽  
Thomas Gruenberger ◽  
Wolf Bechstein ◽  
Hans-Rudolf Raab ◽  
Juergen Weitz ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Tumor Response ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Clinical Trial Information

3538 Background: CRC liver metastases can be resected after downsizing with intensive chemotherapy schedules, with a strong correlation between the response and resection rates. Cetuximab plus chemotherapy has been shown to increase the rates of tumor response and resection of liver metastases. (Van Cutsem et al, JCO 2011). Methods: Patients (pts) with technically non-resectable and/or with > 4 liver metastases were randomized to treatment with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated regarding resectability every 2 months. Resection was offered to all patients who became resectable during the study. K-ras and b-raf status were retrospectively evaluated. Data on tumor response and resection were reported earlier (Folprecht et al, Lancet Oncol 2010). Overall and progression free survival were analyzed in December 2012. Results: Between Dec 2004 and March 2008, 56 pts were randomized to arm A, 55 to arm B. For the current analysis, 109 pts were evaluable for overall survival (OS), and 106 patients for PFS. The median OS was 35.7 [95% CI: 27.2-44.2] months (arm A: 35.8 [28.1-43.6], arm B: 29.0 [16.0-41.9], HR 1.03 [0.66-1.61], p=0.9). The median PFS was 10.8 [9.3-12.2] months (Arm A: 11.2 [7.2-15.3], Arm B: 10.5 [8.9-12.2], HR 1.18 [0.79-1.74], p=0.4). Patients with R0 resection had a better OS (median: 53.9 [35.9-71.9] mo) than patients without R0 resection (27.3 [21.1-33.4] mo, p=0.002) and a better PFS (median 15.4 [11.4-19.5] and 8.9 [6.7-11.1] mo in R0 resected and not R0 resected pts, p<0.001). The 5 year survival in R0 resected patients is 46.2% [29.5-62.9%]. Conclusions: This study confirmed a favourable long term survival of patients with initially “nonresectable” CRC liver metastases treated in a multidisciplinary approach of neoadjuvant chemotherapy with cetuximab and subsequent metastasectomy in pts who became resectable. Clinical trial information: NCT00153998. [Table: see text]

Progression after the next line of therapy (PFS2) and updated OS among patients (pts) with advanced NSCLC and PD-L1 tumor proportion score (TPS) ≥50% enrolled in KEYNOTE-024.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9000-9000 ◽  
Author(s):  
Julie R. Brahmer ◽  
Delvys Rodriguez-Abreu ◽  
Andrew George Robinson ◽  
Rina Hui ◽  
Tibor Csõszi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Advanced Nsclc ◽  
Anticancer Therapy ◽  
Egfr Mutations ◽  
First Line ◽  
Kaplan Meier ◽  
Line Of Therapy ◽  
Clinical Trial Information ◽  
Platinum Doublet

9000 Background: In KEYNOTE-024 (NCT02142738), pembrolizumab (pembro) was superior to chemotherapy (chemo) as first-line (1L) therapy for advanced NSCLC with PD-L1 TPS ≥50% and no sensitizing EGFR mutations or ALK translocations. After a median follow-up of 11.2 mo, HR was 0.50 for PFS by independent central radiologic review ( P< 0.001) and 0.60 for OS ( P= 0.005). Here we present PFS2 and updated OS. Methods: 305 pts were randomly assigned to pembro 200 mg Q3W (n = 154) or investigator (INV)-choice platinum-doublet chemo with optional pemetrexed maintenance for nonsquamous histology (n = 151). Pts in the chemo arm could cross over to pembro upon PD. Poststudy anticancer therapy and INV-assessed outcomes were collected. Kaplan-Meier PFS2 and OS were calculated in all allocated pts. PFS2 was defined as time from randomization to PD per INV after start of 2L+ therapy or death, whichever occurred first; pts alive and without 2L+ PD were censored at last known survival. Kaplan-Meier OS was defined as time from randomization to death. There was no adjustment for multiplicity (cutoff: Jan 5, 2017). Results: 2L+ therapy was received by 48 (31.2%) pts in the pembro arm and 97 (64.2%) in the chemo arm, including 80 pts who crossed over from chemo to pembro per protocol and 14 pts who received anti–PD-1 therapy outside of crossover. 56 (36%) 1L pembro pts were on 1L pembro therapy or in follow-up as of data cutoff. Updated median OS and PFS2 results are in the Table. Conclusions: Fewer pembro pts received 2L+ therapy vs chemo pts because of the significant improvement in PFS observed for pembro in the 1L setting. Median PFS2 was substantially improved for pembro (not reached [NR]) vs chemo (8.6 mo). Updated OS with median follow-up of 19 mo maintained consistent superiority of 1L pembro, despite increased crossover from 1L chemo. Clinical trial information: NCT02142738. [Table: see text]

A single-center retrospective study of patients treated with trabectedin (TRB) with long-term follow up.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11061-11061
Author(s):  
Brett A. Schroeder ◽  
Chad He ◽  
Yuzheng Zhang ◽  
Michael Wagner ◽  
Robin Lewis Jones ◽  
...  
Keyword(s):  
Demographic Variables ◽  
Rank Test ◽  
Prior Chemotherapy ◽  
Pairwise Correlation ◽  
Log Rank Test ◽  
Long Term Follow Up ◽  
Line Of Therapy ◽  
Clinical Trial Information

11061 Background: TRB is FDA approved drug for the treatment of liposarcoma (Lipo) and leiomyosarcoma (LMS). The aim of this study was to evaluate potential biomarkers associated with prolonged benefit in patients treated with TRB at our center prior to 2016. Methods: We performed a retrospective search of UW/FHCRC CASIS database to identify patients treated with TRB prior to 2016. Demographic variables and clinical variables (such as histology and treatment) were retrieved. Statistics were performed with R 3.4.1 software. Pairwise Pearson’s correlation was calculated for the # of prior chemotherapy regimens with # of TRB cycles. The Kaplan-Meir method was used to evaluate overall survival (OS). Log-rank test was conducted to compare groups in terms of OS. Results: 145 sarcoma patients treated with TRB were identified with a mean follow up of 5 years (generally on NCT01427582 or NCT01343277). Patients averaged 1.9 prior chemotherapy regimens prior to TRB (range 0-7 regimens) and received an average of 5.6 TRB doses (range 1-25 doses). Subtypes are listed on table. The # of prior regimens was negatively correlated with the # of TRB cycles that patients received (pairwise correlation coefficient = -1.77; p=0.034), suggesting that multiple prior treatment lines either made TRB less tolerable or made sarcoma less sensitive to TRB. The median OS for this heavily treated metastatic population was 0.5 years. However, patients who were able to stay on TRB for more than 5 cycles had a significantly higher OS (p=0.001). While only 23% of patients who received less than 5 cycles of TRB were alive at 5 years (95% CI: 0.15, 0.32), 53% of those who received 5 or more cycles of (95% CI: 0.39, 0.65) were alive at 5 years. Conclusions: TRB may be more effective when administered as an earlier line of therapy. Patients who are able to stay on TRB for a longer duration had a significant improvement in OS. Detailed subset analysis will be presented as will initial findings of our biomarker work. These retrospective data warrant further evaluation. Clinical trial information: NCT01427582 or NCT01343277. [Table: see text]

scholarly journals Tumor markers cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen for monitoring metastatic breast cancer during first-line chemotherapy and follow-up

1996 ◽  
Vol 42 (4) ◽  
pp. 564-575 ◽  
Author(s):  
G Sölétormos ◽  
D Nielsen ◽  
V Schiøler ◽  
T Skovsgaard ◽  
P Dombernowsky
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Carcinoembryonic Antigen ◽  
Progressive Disease ◽  
Metastatic Breast ◽  
Tissue Polypeptide Antigen ◽  
First Line ◽  
Cancer Antigen ◽  
Line Chemotherapy

Abstract We investigated whether model systems integrating stochastic variation into criteria for marker assessment could be used for monitoring metastatic breast cancer. A total of 3989 serum samples was obtained from 204 patients receiving first-line chemotherapy and from 112 of these patients during follow-up. Each sample was analyzed for cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen. The efficiency for identifying progression and nonprogression was 94% during therapy and 85% during follow-up, with no false-positive marker results for progressive disease. At clinical progressive disease, the median positive lead time was 35 days during therapy and 76 days during follow-up. Tumor marker assessment may document that a therapy is effective and ought to be continued in spite of adverse toxic effects, and that a treatment is ineffective and should be stopped to prevent unnecessary toxicity. Marker information may also be useful in studies investigating whether early treatment during follow-up will alter the prognosis of metastatic breast cancer.

Sign in / Sign up

Export Citation Format

Share Document