Safety and efficacy of chemotherapy in older adults with locally advanced and metastatic pancreatic ductal adenocarcinoma (PDAC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 654-654 ◽  
Author(s):  
Lorena Ostios-Garcia ◽  
Patricia Saade ◽  
Joseph Elan Grossman ◽  
Leanne Lanniello ◽  
Andrea J. Bullock
Keyword(s):  
Older Adults ◽  
Cox Regression ◽  
Performance Status ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Safety And Efficacy ◽  
Exact Test ◽  
Univariate Analyses

654 Background: PDAC is often diagnosed in patients (pts) ≥75yrs. However, older adults comprise a small proportion of subjects in prospective trials, and there is little reported on the safety and efficacy of chemotherapy in this population. Methods: Records were reviewed on all pts ≥75yrs treated with chemotherapy for locally advanced and metastatic PDAC at a single institution from April 2010 - March 2018. Response rate (RR), progression free survival (PFS), overall survival (OS) and toxicities were compared among the different regimens, and among pts < or ≥80yrs. Survival was estimated with the Kaplan-Meier method and compared by log-rank test. Univariate analyses were performed by Fisher’s exact test and multivariate analyses by a Cox-regression model to identify factors associated with PFS and OS in this population. Results: 67 pts were treated, median age 81yrs (range: 75-90), stage III (34, 51%) and IV (33, 49%). Chemotherapy regimens included: gemcitabine alone (39), gemcitabine/nab-paclitaxel (17), gemcitabine/vinorebine (1), FOLFOX (8) and FOLFIRINOX (2). 59 (88%) pts required dose adjustments due to toxicity; no differences by age or regimen. RR, PFS, and OS did not differ by age or regimen (Table), although sample size was small. Age >80yrs was associated with reduced PFS (p 0.03). On univariate analyses liver metastases and performance status (PS)>1 were associated with reduced OS; PS>1 was associated with reduced OS on multivariate analysis. Conclusions: Among pts with locally advanced and metastatic PDAC ≥75yrs, there were no differences in RR, PFS or OS by chemotherapy regimen. PS was the only variable associated with reduced OS. Older adults with PS 0-1 are likely to benefit from chemotherapy for non-resectable PDAC.[Table: see text]

scholarly journals Cisplatin, Cetuximab, and Radiation in Locally Advanced Head and Neck Squamous Cell Cancer: A Retrospective Review

2015 ◽  
Vol 9 ◽  
pp. CMO.S18682 ◽  
Author(s):  
Prakash Peddi ◽  
Runhua Shi ◽  
Binu Nair ◽  
Fred Ampil ◽  
Glenn M. Mills ◽  
...  
Keyword(s):  
Head And Neck ◽  
Performance Status ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Rank Test ◽  
Advanced Head ◽  
Significant Difference ◽  
Group A ◽  
Group B

Efficacy of cisplatin versus cetuximab with radiation in locally advanced head and neck cancer (LAHNC) was evaluated. A total of 96 patients with newly diagnosed LAHNC treated at our institution between 2006 and 2011 with concurrent radiation and cisplatin (group A, n = 45), cetuximab (group B, n = 24), or started with cisplatin but switched to cetuximab because of toxicity (group C, n = 27) were reviewed. Chi-square test, analysis of variance, and log-rank test were used for analysis. The three groups had similar baseline characteristics, except for median age, T stage, albumin levels, hemoglobin levels, performance status, and comorbidities. A complete response (CR) was seen in 77%, 17%, and 67% of patients ( P < 0.001), respectively. There was no significant difference in median overall survival (OS) between groups A and C. The median OS for groups A and C was not reached (>65 months), even though it was significantly longer than median OS for group B (11.6 months; P ≤ 0.001). The 2-year OS in groups A and C is significantly higher than that in group B (70% for groups A and C, 22% for group B). There is no significant difference in progression-free survival (PFS) between groups A and C. The median PFS for these groups was not reached (>62 months), and is significantly longer than that for group B (4.3 months; P ≤ 0.001). The 2-year PFS of group A (67%) and group C (76%) was significantly longer than that of group B (20%). Cisplatin with radiation appears to be more efficacious even in suboptimal dosing than cetuximab with radiation in LAHNC but the two groups were not well matched.

Phase III Study of VCAP-AMP-VECP vs. Biweekly CHOP in Aggressive Adult T-Cell Leukemia-Lymphoma (ATLL): Japan Clinical Oncology Group Study, JCOG9801.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 812-812 ◽  
Author(s):  
Kunihiro Tsukasaki ◽  
Takuya Fukushima ◽  
Atae Utsunomiya ◽  
Syuichi Ikeda ◽  
Masato Masuda ◽  
...  
Keyword(s):  
Cox Regression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Rank Test ◽  
P Value ◽  
Minimization Method ◽  
Adult T Cell Leukemia ◽  
Non Hodgkin Lymphoma

Abstract Background: In our study for non-Hodgkin lymphoma (NHL) in 1980’s (JCOG8701), human T-lymphotropic virus type-1- associated ATLL was the poorest prognostic subtype in NHL. The complete response (CR) rate was 42%, the median survival time (MST) was 8 months, and the 4-yr overall survival (OS) was 12% (Proc ASCO13:378, 1994). Our previous phase II study (JCOG9303) of G-CSF-supported, dose-intensified multi-agent chemotherapy with VCAP (vincristine, cyclophosphamide, doxorubicin, prednisolone), AMP (doxorubicin, ranimustine, prednisolone) and VECP (vindesine, etoposide, carboplatin, prednisolone) with intrathecal prophylaxis for aggressive ATLL, showed promising results with response rate (RR) of 81% and MST of 13 months (Br J Haematol113:375,2001). To test the superiority of this VCAP-AMP-VECP regimen over biweekly-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), we conducted a phase III trial. Methods: Previously untreated patients (pts) with aggressive ATLL, acute-, lymphoma- or unfavorable chronic-type, were randomized either to receive 6 courses of VCAP-AMP-VECP every 4 weeks (arm A) or 8 courses of biweekly-CHOP (arm B) with minimization method balancing performance status and institution. Both regimens were supported with G-CSF and intrathecal prophylaxis using cytarabine, methotrexate and prednisolone. Eligibility included preserved organ functions and aged 15–69 years. Primary endpoint was OS to be compared by log-rank test. Assuming 60 eligible pts in each arm, the study had 0.8 power to detect a 15% difference in 3-year OS at 0.05 one-sided alpha. Results: 118 pts (57 in arm A, 61 in arm B) were randomized between 07/98 and 10/03. Median follow-up time in all randomized pts was 11.0 months at 12/04. 72 % of the pts responded, with 23 pts achieving CR (40%) and 18 achieving partial response (PR; 32%) in arm A. The RR was 66%, with 15 pts achieving CR (25%) and 25 achieving PR (41%) in arm B. The median progression-free survival (PFS) time and PFS at one-year in arm A were 7.0 months and 28.1%, respectively, whereas 5.4 months and 16.2% in arm B. The MST and OS at 3 years in arm A were 12.7 months and 23.6%, respectively, whereas 10.9 months and 12.7% in arm B. Log-rank p-value for primary end point, OS, was 0.085. After adjustment of patients’ characteristics at registration by Cox regression, the p value became 0.029 because of unbalanced prognostic factors such as bulky lesion. In arm A vs. arm B, %G4 neutropenia, %G4 thrombocytopenia and %G4 infection were 98% vs. 83%, 74% vs. 17% and 7% vs. 3%, respectively. Three toxic deaths were reported in arm A. Conclusions: These results demonstrate that VCAP-AMP-VECP yields longer OS time than biweekly-CHOP but with higher toxicity profiles that are acceptable, and suggest that the former regimen should be the standard therapy for aggressive ATLL.

The prognostic value of polymorphisms in the insulin-like growth factor receptor (IGFR) pathway in patients with locally advanced pancreatic cancer (LAPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4500-4500
Author(s):  
R. T. Shroff ◽  
M. M. Javle ◽  
X. Dong ◽  
V. S. Kumar ◽  
S. Krishnan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Induction Chemotherapy ◽  
Prognostic Value ◽  
Cox Regression ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Rank Test ◽  
Cox Regression Analysis

4500 Background: The IGFR pathway is activated in pancreatic cancer and may result in aggressive disease course. The study of single nucleotide polymorphisms (SNPs) involved in this pathway may provide prognostic information and predict response to IGFR directed agents. We investigated IGFR pathway SNPs in patients with LAPC. Methods: We evaluated 39 SNPs from 7 candidate genes in the IGFR pathway (IGF1R, IGF2R, IGF1, IGF2, IRS1, IRS2, IGFBP3) in 105 LAPC patients. DNA extraction from whole blood was performed using the Qiagen Flexigene DNA and Promega Maxwell 16 kits. Genotyping was performed using the Sequenom method. Overall survival was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare survival of patients according to genotype corrected for previously identified prognostic factors, including induction chemotherapy, CA 19–9, albumin, LDH, hemoglobin and Karnofsky performance status (KPS). Results: Median survival time (MST) was 15 months (95% CI 13.3–16.7). Induction chemotherapy, LDH, CA 19–9 level, hemoglobin, and KPS were not significantly associated with survival. Serum albumin and three SNPs of the IGF pathway (IGF1R IVS20–3431A>G, IRS1 G971R, and IGF2 *4352A>G) were significantly associated with prognosis ( Table ). Two of the three genotypes remained as significant predictors for survival in Cox regression analysis when adjusted for clinical factors. A significant combined genotype effect was observed wherein patients with all three deleterious alleles had significantly worse survival than those with only two or one (10 vs. 16.3 vs. 21.3 months, p< 0.0001). Conclusions: These data suggest that SNPs in the IGFR pathway genes may have prognostic value for LAPC patients. This information may identify population subgroups that could benefit from IGFR-targeted agents. [Table: see text] No significant financial relationships to disclose.

Cisplatin (CDDP) and radiation versus cetuximab (Cx) and radiation in locally advanced head and neck squamous cell cancer (SCHNC): A retrospective review.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16009-e16009 ◽  
Author(s):  
Prakash Peddi ◽  
Runhua Shi ◽  
Lori Panu ◽  
Fred Ampil ◽  
Cherie-Ann Nathan ◽  
...  
Keyword(s):  
Performance Status ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Rank Test ◽  
Cancer Center ◽  
Ecog Performance Status ◽  
Chi Square ◽  
Group A

e16009 Background: SCHNC is a common malignancy and approximately 60% of patients present with locally advanced disease. There is paucity of data directly comparing Cx and CDDP with concurrent radiation in locally advanced SCHNC. We retrospectively reviewed charts of patients treated with CDDP and/or Cx along with radiation in locally advanced SCHNC comparing efficacy and outcomes in an academic cancer center. Methods: Ninety-five patients with locally advanced SCHNC were treated with concurrent CDDP (100 mg/m2 day 1, 22, 43) or Cx (400mg/m2 on day -7 and 250mg/m2 weekly) at our institution between January 2006 and June 2011. Forty-four patients were treated with CDDP (group A), 24 with Cx (group B) and 27 were initially started on CDDP but were switched to Cx secondary to toxicity (group C). All patients received concurrent radiation treatments (66-70 Gy, 2.0 Gy/fraction). The selection of CDDP versus Cx was largely based on ECOG performance status (PS) and baseline renal function of the patients. Chi-square test, analysis of variance, and log-rank test was used for analysis. The three groups had similar baseline characteristics except for mean age of 61, 56 and 55 years in group A, B and C respectively; T4 tumors consisted of 44%, 75% and 41% in groups A, B and C respectively. Groups A, B and C had a combined ECOG 0 and I (PS) of 93%, 75% and 92%. Patients with ECOG III PS were excluded. Results: Oropharynx was the most common treated site (38%) followed by Larynx (35%). Complete response (CR) was seen in 77%, 17% and 67% in groups A, B and C respectively (P<0.001). Median progression free survival (PFS) was 16.6, 4.3 and 22.8 in groups A, B and C respectively (P<0.001) and median overall survival (OS) was >35, 11.6 and >32 months in groups A, B and C respectively (P<0.0001). Conclusions: Concurrent CDDP with radiation leads to better response rate PFS and OS as opposed to Cx though many patients treated with CDDP could not complete treatment due to toxicity. Randomized trial comparing the two should be considered.

Efficacy and safety of FOLFIRINOX in elderly patients with advanced pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15729-e15729
Author(s):  
Jae Hyup Jung ◽  
Jingu Kang ◽  
Jong-Chan Lee ◽  
Jin-Hyeok Hwang
Keyword(s):  
Elderly Patients ◽  
Performance Status ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Elderly Group ◽  
Ductal Adenocarcinoma ◽  
First Line ◽  
Tertiary Teaching ◽  
Group A ◽  
Group B

e15729 Background: Although FOLFIRINOX showed improved efficacy in advanced pancreatic ductal adenocarcinoma (PDA), physicians still hesitate to administrate FOLFIRINOX in elderly patients despite of being in a good performance status. We investigated the efficacy and toxicity of FOLFIRINOX in elderly patients with advanced PDA. Methods: We retrospectively reviewed electronic medical records of advanced PDA patients administrated a first-line FOLFIRINOX from January 2012 to July 2017 in a single tertiary teaching hospital. All the patients were divided into two groups: non-elderly group A (age < 70) and elderly group B (age≥70). Overall survival (OS), progression free survival (PFS) and toxicities were compared between two groups using Cox proportional hazard model. Results: A total of 214 patients (Group A 176; B 38) met the eligible criteria. Median age was 61 years old (29-80, group A 59; B 73) and median cycle of FOLFIRINOX was 7.0 (1–75, group A and B 7.0). Median OS and PFS did not differ between group A and B (OS, 11.8 vs 12.0 months, hazard ratio [HR] 1.165, 95% confidence interval [CI] 0.785–1.728; PFS 6.5 vs 7.3 months, HR 1.003, 95% CI 0.694–1.451, respectively). When we analyzed OS according to tumor stage (locally advanced and metastatic), group A and B showed comparable median OS (15.8 vs 13.5 months in locally advanced PDA; 8.6 vs 9.8 months in metastatic PDA, respectively) There were no significant differences in terms of hematologic toxicities except Gr 3 or 4 thrombocytopenia (Group A 3.4%; B 13.2%, P = 0.028). Fatigue and diarrhea were observed more often in Group B than in group A (47.4% vs 10.2%, P = 0.000; 18.4% vs 4.5%, P = 0.010, respectively), all of which were manageable. More patients in group B received dose adjusted FOLFIRINOX than in group A, although there was no statitical significance. Conclusions: FOLFIRINOX could be considered as the first-line chemotherapy for elderly patients with advanced PDA as well as non-elderly patients when dosage modified appropriately, given comparable efficacies and acceptable and manageable toxicities. More studies are warranted to confirm this issue.

Association of immune related adverse events with superior outcomes in patients with hepatocellular carcinoma (HCC) treated with nivolumab.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16630-e16630
Author(s):  
Lorena Ostios-Garcia ◽  
David Ramiro-Cortijo ◽  
Mary Linton Bounetheau Peters ◽  
Andrea J. Bullock
Keyword(s):  
Adverse Events ◽  
Cox Regression ◽  
Statistical Significance ◽  
Onset Time ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
Rank Test ◽  
Cancer Outcomes ◽  
Exact Test ◽  
Kaplan Meier

e16630 Background: Nivolumab, an anti-PD1 antibody, is FDA approved in patients (pts) with HCC. Anti-PD-1 promotes hyperstimulation of host immunity and is associated with a spectrum of toxicities known as immune-related adverse events (irAEs). In other malignancies, higher rates of irAEs are associated with improved cancer outcomes. This study shows correlation between irAEs and efficacy in pts with HCC treated with nivolumab. Methods: Demographic and toxicity data were collected retrospectively on all pts with HCC treated with nivolumab at a single institution from Jan 2012 – Sept 2019. Response was evaluated using RECISTv1.1. Adverse events were assessed according to CTCAEv5.0. Categorical variables were assessed by Fisher's exact test. Survival was estimated with the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed by the Cox-regression model. Results: 30 pts were treated; irAEs were detected in 16 (53%). There was no difference in baseline characteristics among those who did and did not experience irAEs (Table). The most frequent irAEs were elevated AST/ALT (n = 7; 44%), rash (n = 4; 25%), and hypothyroid (n = 4; 25%). 3 G3 (rash and transaminitis) and 1 G4 AE (pured red cell apalasia) were observed. Among all pts, overall response rate (RR) and disease control rate (DCR) were 13 and 50%, respectively. Median progression free survival (PFS) and overall survival (OS) were 27 and 56 weeks (w), respectively. The RR and DCR were higher among irAEs vs non-irAEs, although this did not reach statistical significance (RR 25 vs 0%; p = 0.05; DCR 62 vs 35%; p = 0.19). Median PFS and OS were longer in those with irAEs vs non-irAE; PFS 33 vs 16 w (HR: 0.26; CI 95%: 0.076-0.89; p = 0.028); (OS 69 vs 21 w HR: 0.18; CI 95%: 0.05-0.58; p = 0.002). On multivariate analysis, viral etiology was associated with prolonged PFS (p = 0.002) and MELD was associated with reduced OS (p = 0.004). Conclusions: Development of irAEs was associated with prolonged PFS and OS in pts with HCC treated with nivolumab. Further study is needed to determine whether type of irAE, onset time, or duration affect cancer outcomes. [Table: see text]

Efficacy and safety of second-line nab-paclitaxel plus gemcitabine (nab-P+GEM) after progression on first-line FOLFIRINOX in advanced pancreatic ductal adenocarcinoma (PDAC): Multicenter retrospective analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 689-689
Author(s):  
Changhoon Yoo ◽  
Hyehyun Jeong ◽  
Heejung Chae ◽  
Jaekyung Cheon ◽  
Hong Jae Chon ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Retrospective Analysis ◽  
Performance Status ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Daily Practice ◽  
Common Adverse Event ◽  
Ductal Adenocarcinoma ◽  
Ecog Performance Status ◽  
Line Therapy

689 Background: FOLFIRINOX is one of standard 1st-line regimens for patients (pts) with advanced PDAC. However, there is no globally established 2nd-line regimen after failure of FOLFIRINOX. Although gemcitabine-based regimens are recommended by multiple guidelines and widely used in daily practice, further analysis is needed to reveal the magnitude of clinical benefit with these regimens. Nab-P+Gem is another standard 1st-line regimen for PDAC, but there are limited data as 2nd-line therapy in PDAC. Therefore, we conducted multicenter retrospective analysis of 2nd-line nab-P+Gem after progression on FOLFIRINOX in pts with advanced PDAC. Methods: Between Feb 2016 and Feb 2019, a total of 103 pts with histologically documented PDAC who received nab-P+GEM after progression on 1st-line FOLFIRINOX were identified among 5 referral cancer centers in South Korea. Results: Median age was 60 years and 50 pts (49%) were male. All but one pts had ECOG performance status of 0-1 at the time of nab-P+GEM. At the time of nab-P+GEM, 25 (24%) and 78 (76%) patients had locally advanced and metastatic disease, respectively. Median overall survival (OS) and progression-free survival (PFS) with nab-P+GEM was 9.8 months (95% CI: 8.9-10.6) and 4.6 months (95% CI: 3.7-5.5), respectively. Among pts with measurable disease (n = 95), partial response and stable disease were achieved in 8 (8%) and 56 (54%), respectively. Median OS from the start of 1st-line FOLFIRINOX was 20.9 months (95% CI: 15.2-26.6). Most common adverse event of all grade was anemia (77%), followed by neutropenia (60%), fatigue (52%), thrombocytopenia (45%), and peripheral neuropathy (30%). Most common grade 3-4 adverse events were neutropenia (36%), anemia (9%), and peripheral neuropathy (8%). Conclusions: In medically fit pts with advanced PDAC who failed on 1st-line FOLFIRINOX, nab-P+GEM was effective and well tolerated as 2nd-line therapy.

Updated results of a phase III trial comparing standard thoracic radiotherapy (RT) with or without concurrent daily low-dose carboplatin in elderly patients (pts) with locally advanced non-small cell lung cancer (NSCLC): JCOG0301.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7017-7017 ◽  
Author(s):  
Hiroaki Okamoto ◽  
Shinji Atagi ◽  
Masaaki Kawahara ◽  
Akira Yokoyama ◽  
Nobuyuki Yamamoto ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Cox Regression ◽  
Smoking Status ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Concurrent Chemotherapy ◽  
Phase Iii ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Locally Advanced Nsclc

7017 Background: We previously reported the superiority of combined chemo-radiotherapy (CRT) over RT alone in elderly pts with locally advanced NSCLC (Atagi et al. ECCO2011). One and a half years follow-up data from last accrual are presented. Methods: Pts older than 70 years with unresectable stage III NSCLC were randomized to either RT alone (RT arm), a total dose of 60 Gy, or CRT arm including the same RT plus concurrent chemotherapy with carboplatin 30 mg/m2/day, 5 days/week × 20 days. The primary endpoint was overall survival (OS). The planned sample size was 100 pts in each arm with one-sided alpha of 5% and 80% power to detect a difference in median survival time (MST) from 10 months in RT arm to 15 months in CRT arm. Results: Between Sep 2003 and May 2010, 200 pts were randomized. Baseline characteristics were similar in the RT (n=100) vs CRT (n=100) arms: median age, 77 vs 77 years; stage IIIB (n), 46 vs 49; PS 0/1/2 (n), 41/55/4 vs 41/56/3. The second planned interim analysis was performed 10 months after the completion of accrual. In accordance with the pre-specified stopping rule, the JCOG Data and Safety Monitoring Committee recommended early publication of this trial because of the difference in OS favoring the CRT arm. In the updated analysis, OS was better in the CRT arm than the RT arm (HR = .64, 95% CI = .46-.89, one-sided p = .0033 by stratified log-rank test). In each arm (RT/CRT), MST was 16.5 mo/22.4 mo with 3-year OS of 14.3%/34.6%, response rate of 44.9%/54.6% (p=.201) and median progression-free survival of 6.9 mo/8.9 mo (p=.003). Gr 3/4 toxicities were (RT/CRT): neutropenia 0%/57.3%, infection 4.1%/12.5%, dysphagia 0%/1.0%, late RT toxicities 7.4%/7.5%. The pattern of relapse site and post-protocol treatment were almost similar between the arms. Even after an adjustment by the Cox regression analysis with six variables [stage, PS, sex, age, histology, smoking status], CRT arm showed better survival (HR=.71, p=.038). Conclusions: The CRT using daily carboplatin is considered to be the standard treatment for elderly pts with locally advanced NSCLC.

Quality-of-life (QoL) in RANGE: A phase 3 study of ramucirumab (RAM) plus docetaxel (DOC) versus placebo (P) plus DOC in platinum-refractory locally advanced or metastatic urothelial carcinoma (UC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 419-419 ◽  
Author(s):  
Andrea Necchi ◽  
Hiroyuki Nishiyama ◽  
Nobuaki Matsubara ◽  
Jae-Lyun Lee ◽  
Daniel Peter Petrylak ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Median Number ◽  
Rank Test ◽  
Point Change ◽  
Exact Test ◽  
Eortc Qlq C30 ◽  
Platinum Refractory ◽  
Eortc Qlq

419 Background: RAM + DOC in RANGE (NCT02426125) improved progression free survival (hazard ratio [HR] = 0.757) with a higher objective response rate (24.5% vs 14%) and an acceptable safety profile (Petrylak, et al Lancet 2017). QoL was a secondary objective. Methods: Patients (pts) whose UC progressed following platinum-based therapy were randomized to receive RAM (10 mg/kg) + DOC (75 mg/m2) or P + DOC on Day 1 of a 21-day cycle. Treatment continued until disease progression or unacceptable toxicity with a maximum of 10 cycles for DOC. Pts completed the EORTC QLQ-C30 (v3) prior to each cycle & at the 30-day follow up visit. QoL scales were analyzed for: 1) rates of improved/stable scores (compared with Fisher’s exact test) & 2) time to sustained deterioration (TtD), defined as randomization to first worsening with no subsequent non-worsened assessment (compared with unstratified log-rank test). A ≥10 point change (on 100-point scale) was deemed clinically meaningful. Results: 530 pts were randomized. 254/263 (97%) RAM-DOC & 260/267 (97%) P-DOC pts provided baseline (BL) QoL data & ≥85% for post-BL, on-therapy assessments. Median number of cycles was 4 for RAM-DOC & 3 for P-DOC. Mean BL scores were similar between arms & indicated greatest impairment for global QoL, fatigue, pain, & insomnia. For all scales, rates of improved/stable scores were not different, except for pain at Cycles 4 & 7 where rates were higher for RAM-DOC (p < 0.05). Relative to other QoL scales, pain generally had highest rates of improved scores in both arms (14-25% for RAM-DOC & 8-24% for P-DOC for Cycles 1-4). In a post hoc analysis, Cycles 1-4 rates of improved pain scores were 31-32% for RAM-DOC & 14-26% for P-DOC in tumor responders, but 17-29% for RAM-DOC & 16-28% for P-DOC in pts with stable disease. For TtD, 14/15 QoL scales had HRs < 1, indicating similar or numerically longer TtD in QoL for RAM-DOC (HRs 0.67- 1.06; all 95% confidence intervals included 1). Conclusions: The addition of RAM to DOC for platinum-refractory UC pts did not adversely impact QoL relative to P-DOC. Trends in improved TtD and improved rates of pain associated with tumor response favored RAM-DOC. Clinical trial information: NCT02426125.

Impact of KRAS alterations in pancreatic ductal adenocarcinoma (PDAC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4136-4136
Author(s):  
Maahum Mehdi ◽  
Mandana Kamgar ◽  
Ben George ◽  
Aniko Szabo ◽  
Kaitlin Annunzio ◽  
...  
Keyword(s):  
Cox Regression ◽  
Survival Curve ◽  
Locally Advanced ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Great Promise ◽  
Study Cohort ◽  
Genomic Alterations ◽  
Borderline Resectable ◽  
Kras Mutations

4136 Background: The genomic alterations which characterize PDAC holds great promise for novel therapeutic interventions. Constitutive signaling via mutated KRAS is considered the signature pathognomonic alteration in PDAC, less than 10% of patients (pts) have tumors which are KRAS wild type (WT). We retrospectively reviewed our institutional genomic database to characterize PDAC pts with KRAS WT tumors. Methods: We reviewed electronic medical records of PDAC pts who underwent comprehensive genomic profiling (CPG) utilizing Foundation One CDx (50.6%) or TEMPUS (49.4%) between 2015-2020. Demographic and disease characteristics were compared between cohorts using Wilcoxon rank-sum test or chi-square tests. Left truncation at the time of CGP was used to account for the time of entry into the study cohort. Kaplan-Meier method was used for survival curve estimation, and log-rank test was used for between-group comparison. Cox regression was used to adjust for confounders. Results: We identified 235 patients: median age at diagnosis was 65 years and 52% were male. Clinical stages at diagnosis were localized (resectable/borderline resectable), locally advanced, or metastatic in 105 (44.7%), 61 (26.0%), and 69 (29.4%) patients, respectively. KRAS status was mutated in 212 (90%) patients: the most common alterations being G12D (48%), G12V (28%) and G12R (14%). KRAS WT status was noted in 23 (9.8%) pts, actionable genomic alterations in this subgroup are summarized in the table. Baseline demographic and treatment characteristics were similar between patients with KRAS mutated and WT tumors. Of the 23 patients with KRAS WT tumors, 16 (69.6%) completed all planned curative intent therapy compared to 121 (57.3%) of the 212 KRAS mutated pts (p=0.26). Median Overall Survival of patients with KRAS mutated tumors was 18.6 months compared to 44.1 months for WT pts (p=0.03). Adjusting for stage, WT vs. mutated status was associated with a 62% decreased hazard of death (HR 0.38 [0.18-0.83]; p=0.016). Conclusions: Patients with KRAS WT PDAC appear to have a distinct biology compared to those with KRAS mutations, meriting exploration in larger data sets. Further, comprehensive whole genome or transcriptomic characterization of KRAS WT tumors is necessary to identify putative driver alterations as well as actionable therapeutic targets.[Table: see text]

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