Real-world outcomes of underrepresented patient populations treated with immune checkpoint inhibitors (ICIs): African American descent, poor ECOG performance status, and chronic viral infections.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2587-2587 ◽  
Author(s):  
Neil J. Shah ◽  
Matthew Blackburn ◽  
Michael R Cook ◽  
Anas Belouali ◽  
Michael Serzan ◽  
...  
Keyword(s):  
African American ◽  
Viral Infections ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Outcome Data ◽  
Viral Reactivation ◽  
Ecog Performance Status ◽  
Chronic Viral Infections ◽  
Grade 3 ◽  
Ecog Ps

2587 Background: ICIs have now become standard of care treatment for multiple malignancies. However, patients (pts) who are African American decent (AA), have a poor ECOG performance status (PS) or chronic viral infections [human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV)] were underrepresented in early clinical trials with ICIs and outcome data in these pt populations is not well reported. Methods: We performed a retrospective analysis of pts treated with ICIs (anti-PD(L)-1, anti-CTLA-4, or combination ICIs) across five MedStar Health hospitals from January 2011 to April 2018. Investigator-assessed best responses were noted. CTCAE v4.03 was used to capture immune-related adverse events (irAEs). Results: We identified 765 pts treated with 829 unique ICIs therapies across different malignancies. A total of 203 AA pts, 178 pts with a pre-treatment ECOG PS ≥2, 21pts with HIV, and 50 pts with HBV/HCV were noted. Any grade and grade ≥ 3 irAEs in the HIV cohort were 24% and 10% with an ORR of 29%. Any grade and grade ≥ 3 irAEs in HBV/HCV were 50% and 26% with an ORR of 21%. No viral reactivation or changes in pts anti-viral medications were noted during ICIs treatment. The ORR in AA pts was 35%. Any grade and grade ≥ 3 irAEs in the AA cohort were 27% and 8%, respectively. The ORR in pts with ECOG PS ≥2 was 14%. Any grade and grade ≥ 3 irAEs in this cohort were 20% and 4%. Similar trends were seen in the subset of patients with NSCLC treated with anti-PD(L)1 monotherapy (Table). Outcomes of NSCLC pts treated with anti-PD(L)-1 monotherapy. Conclusions: ICI therapy was not associated with any new safety signal in the above underrepresented populations. Prospective studies are needed to validate this data.[Table: see text]

DREAMseq (Doublet, Randomized Evaluation in Advanced Melanoma Sequencing): A phase III trial—ECOG-ACRIN EA6134.

2021 ◽  
Vol 39 (36_suppl) ◽  
pp. 356154-356154
Author(s):  
Michael B. Atkins ◽  
Sandra J. Lee ◽  
Bartosz Chmielowski ◽  
Antoni Ribas ◽  
Ahmad A. Tarhini ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Initial Therapy ◽  
Phase Iii ◽  
Treatment Sequence ◽  
Ecog Performance Status ◽  
Randomized Evaluation ◽  
Alternate Therapy ◽  
Treatment Naïve ◽  
Grade 3

356154 Background: Combinations of immune checkpoint inhibitors (CPI) blocking PD-1 and CTLA-4 or BRAF/MEK inhibitors have both shown significant antitumor efficacy and overall survival (OS) benefit in patients (pts) with BRAFV600-mutant metastatic melanoma (MM), leading to broad regulatory approval. Little prospective data exists to guide the choice of one over the other as initial therapy or the preferred treatment sequence in this population. The DREAMseq Trial was designed to compare the efficacy and toxicity of the sequence of nivolumab/ipilimumab (N/I) followed by dabrafenib/trametinib (D/T) to the converse sequence. Methods: Eligible pts with treatment-naive BRAFV600-mutant MM were stratified by ECOG Performance Status (PS) 0 or 1 and LDH level and randomized 1:1 to receive Step 1 with either N/I (Arm A) or D/T (Arm B) and at disease progression (PD) were enrolled in Step 2 receiving the alternate therapy, D/T (Arm C) or N/I (Arm D), respectively. Pts received N (1mg/kg)/I (3 mg/kg) q3 wks x 4 doses followed by N 240 IV q2 wks for up to 72 wks (Arms A and D) or D 150 mg po BID and T 2 mg po qD until PD (Arms B and C). In 2019, investigators were given the option to use alternate induction dosing of N (3mg/kg)/I (1 mg/kg) q3 wks x 4 doses for Arms A and D. Cycles were every 6 wks and imaging was obtained at baseline and q12 wks on each arm. Primary endpoint was 2-year OS. At the 4th Interim Analysis with 59% of pts being 2 yrs from enrollment, the DSMC and NCI CTEP recommended halting accrual and releasing the data. Results: Beginning 7/2015, 265 out of a proposed 300 pts were enrolled (133 Arm A and 132 Arm B). Median age was 61 (25-85) and 63% were male. Demographics for Arm A and B were balanced with 67% PS 0 and 60% with normal LDH. As of 7/16/21, at a median follow-up of 27.7 mos, 27 pts had switched to Arm C and 46 to Arm D. Overall Grade 3+ toxicity was 60% in Arm A and 52% in Arm B. Grade 5 treatment-related AEs included 2 on Arm A and 1 on Arm C. ORR to date is: Arm A 46% (52/113), Arm B 43% (49/114), Arm C 48% (11/23) and Arm D 30% (8/27). 37/42 assessed pts in Arm A and 19/37 in Arm B remain in response. Median DOR: Arm A- Not reached; Arm B-12.7 mos (95% CI: 8.2, -) (p <0.001). There were 100 deaths (Arm A to C- 38/Arm B to D- 62). 2-yr OS rate for those starting with Arm A was 72% (95% CI: 62-81%) and for Arm B 52% (95% CI: 42-62%) (log-rank p= 0.0095). PFS showed a trend in favor of Arm A (log-rank p=0.054). Both the PFS and OS curves show a biphasic pattern with Arm B being above Arm A until 6 and 10 mos, respectively. For the 115 pts with documented progression on Step 1 (Arm A-44/Arm B-71), 60 (52%) had registered for Step 2. The principal reason for not enrolling on Step 2 was death from PD within 6 mos (Arm A:15/23; Arm B: 25/32). Conclusions: For pts with advanced BRAFV600-mutant MM, the treatment sequence beginning with the CPI combination of N/I resulted in superior OS, which became evident at 10 mos, with longer Step 1 DOR and more ongoing responses than the treatment sequence beginning with D/T. Clinical trial information: NCT02224781.

A phase II trial of irinotecan, 5-fluorouracil and leucovorin in patients with previously untreated advanced colorectal cancer (CRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14599-14599
Author(s):  
N. Lee ◽  
S. Bae ◽  
S. Lee ◽  
D. Kim ◽  
K. Kim ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Tumor Control ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Ecog Ps

14599 Background: We prospectively conducted a phase II trial to test the efficacy and safety of irinotecan, 5-fluorouracil and leucovorin (FOLFIRI) regimens for the first-line treatment of previously untreated patients with recurrent or metastatic advanced CRC. Methods: Thirty-four previously untreated patients with advanced CRC were enrolled in this study from June 2001 to December 2006. Eligible patients had histologically confirmed adenocarcinoma, no prior systemic therapy in palliative setting, ECOG PS = 2, adequate organ function, written informed consent and at least one measurable disease. The patients received either irinotecan 180 mg/m2 on day 1 with a LV bolus of 200 mg/m2 and a FU bolus of 400 mg/m2, and this was followed by a FU continuous infusion of 600 mg/m2 on day 1 and day 2 (the classic FOLFIRI regimen), or they were treated with a LV bolus of 400 mg/m2 and a FU bolus of 400 mg/m2 followed by a FU continuous infusion of 2,400 mg/m2 for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression. Results: There were 13 females and 21 males with median age of 54 years (range: 41–79). The most common metastatic sites were lung and liver. A total of 262 cycles were administrated with median 6 cycles per patient (range: 1–22). All pts were evaluable for toxicity, and 30 pts for response to the treatment. The objective response rate was 26.4% with 2 complete responses respectively. Sixteen (47%) pts had stable disease and 7 (20.5%) had a progression. The tumor control rate was 73.4%. The median TTP was 5.3 months, and the overall survival was 10.1 months. The prognostic factor for longer TTP and survival was the ECOG performance status (PS). The type of regimens was not affected on response rate, TTP and survival. The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia, diarrhea. The non- hematological toxicities were similar for both treatment groups, with more frequent grade =3 neutropenia being noted for the simplified FOLFIRI regimen. Conclusions: The FOLFIRI regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and tend to show more favorable outcome for patients with good ECOG PS. No significant financial relationships to disclose.

Phase II study of S-1 in patients with gemcitabine resistant advanced pancreatic carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14070-14070 ◽  
Author(s):  
K. Sudo ◽  
T. Yamaguchi ◽  
T. Ishihara ◽  
K. Nakamura ◽  
H. Saisho
Keyword(s):  
Pancreatic Carcinoma ◽  
Performance Status ◽  
Rest Period ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Advanced Pancreatic Carcinoma ◽  
Grade 3 ◽  
Ecog Ps

14070 Background: S-1 is an oral fluoropyrimidine derivative with reported response rate of 21.1∼37.5% for advanced pancreatic carcinoma (Ueno, Oncology 2005; Furuse, ASCO 2005). The primary objective of this study was to assess the efficacy and safety of S-1 in patients with gemcitabine resistant advanced pancreatic carcinoma. Methods: Patients with histologically or cytologically proven, metastatic pancreatic carcinoma who had failed prior chemotherapy with gemcitabine were eligible for this study. Other eligibility criteria included an ECOG performance status (PS) of 2 or less; an age of at least 20 years; adequate organ function; and written informed consent. S-1 was administered orally at a dose of 40 mg/m2 twice daily for 28 days, followed by a 14-day rest period. Treatment was repeated every 6 weeks until disease progression. Results: Seventeen patients were enrolled with the following characteristics: median age 67 (range 40–75); male/female = 9/8; ECOG PS 0/1/2 = 1/8/8. All patients were included in analysis. Treatment was generally well tolerated and no life threatening toxicity was observed. Grade 3–4 toxicities were anorexia (17.6%) and fatigue (5.9%). Common grade 1–2 toxicities were anorexia (35.3%), anemia (35.3%), leukocytopenia (29.4%) and diarrhea (23.5%). Three patients were discontinued S-1 because of toxicities. Out of the 17 eligible patients, 3 patients (17.6%) achieved a partial response and 5 patients (29.4%) had stable disease. A marked decrease (≥50%) in tumor markers was observed in 5 (29.4%) of the patients. (CA 19–9 in 3 patients, CEA in 1 patient, DUPAN-2 in 1 patient) The median progression-free survival and the median survival time from the date of initiation of S-1 were 4.1 months (95% CI, 2.0 to 6.2 months) and 5.7 months (95% CI, 2.6 to 8.7 months), respectively. Conclusions: S-1 is well tolerated and active in patients with gemcitabine resistant advanced pancreatic carcinoma. Further investigation of this treatment appears warranted. No significant financial relationships to disclose.

Real-world outcomes of treatment with immune checkpoint inhibitors in unique patient cohorts: Elderly, non-caucasian race, poor performance status, obese, chronic viral infections, and autoimmune diseases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2641-2641
Author(s):  
Neil J. Shah ◽  
Shuo Wang ◽  
Aquino Williams ◽  
Melinda Weber ◽  
Brittany Sinclaire ◽  
...  
Keyword(s):  
Viral Infection ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Viral Infections ◽  
Checkpoint Inhibitors ◽  
Chronic Viral Infection ◽  
Poor Performance Status ◽  
Chronic Viral Infections ◽  
Ecog Ps

2641 Background: Immune Checkpoint Inhibitors (ICI) have revolutionized current cancer treatment. Nevertheless, outcomes data across various patient cohorts are lacking. To address this knowledge gap, we conducted a comprehensive analysis of real-world data (RWD) that included patient cohorts traditionally underrepresented in clinical trials. Methods: We identified patients (pts) treated with ICI (anti-CTLA-4, anti-PD(L)1 or their combination at 6 US academic and community hospitals from 1/2011 – 4/2018. Clinical data obtained from EHR and CTCAE V4.03 was used to define immune-related adverse events (irAEs). Results: A total of 1332 pts treated with 1443 unique ICI treatments were included in the cohort. The median age was 66 (21-87), Male 58% (827), Caucasian 70% (1004), African American (AA) 16% (232), other race 14% (207), ECOG PS 0,1 79% (1130), chronic viral infection 5% [hepatitis B (24), hepatitis C (32) and HIV (17)], with BMI > 30 22% (287) and autoimmune disease (AID) 15% (215). Lung cancer (NSCLC) 34% (423), and melanoma 27% (389) were top 2 tumor types and nivolumab 38% (544), pembrolizumab 23% (332), and ipilimumab plus nivolumab 12% (180) were the most common ICI treatments. Overall survival (OS) was worse for patients with ECOG ≥2 (0.34 - 0.63) vs. ECOG 0,1 (1.27 - 1.73, P <0.001), and better with AID (1.21 - 2.63) vs. no AID ( 0.90 - 1.24, P=0.01) and Caucasian (1.02 - 1.45) vs AA (0.72 - 1.30, P=0.02). No difference in OS was noted for sex, other races, h/o chronic viral infection or obesity. We performed an analysis of OS and irAEs restricted to NSCLC patients (n=423); (N=447 unique ICI treatments); age >75 27% (120), AA 28% (124), Female 50% (224), ECOG PS ≥2 23% (104), BMI >30 15% (62), chronic viral infections 10% (44), and AID 14% (62). The ICI therapies were nivolumab 55% (245), pembrolizumab 23% (102), and atezolizumab 6% (27) and 16% (others). Data is contained in the table. Conclusions: Overall, in our RWD, OS appeared to be similar across above cohorts except poor OS for pts with ECOG ≥2. irAEs also appeared to be similar across cohorts except less with ECOG ≥2. In NSCLC cohort, we noted similar findings except less irAEs in Male cohort. Prospective studies are needed to confirm the above findings.[Table: see text]

Preliminary results for the combination of docetaxel, oxaliplatin and capecitabine as a first-line treatment for metastatic oesophagogastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14076-14076
Author(s):  
S. Viteri ◽  
J. Rodríguez ◽  
M. González Cao ◽  
J. De La Cámara ◽  
A. Chopitea ◽  
...  
Keyword(s):  
Performance Status ◽  
Median Number ◽  
New Drugs ◽  
Phase Ii Trials ◽  
First Line ◽  
Ecog Performance Status ◽  
Standard Regimen ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Ecog Ps

14076 Background: Chemotherapy remains the main treatment option for metastatic oesopagogastric cancer (MOC) patients (Pts). First-line regimens have proved a slight but significant increase in quality of life and survival, but a standard regimen has not been defined yet. Several new drugs, as Docetaxel (D), Oxaliplatin (O) and Capecitabine (C) have demostrated activity in MOC. They have shown synergy in preclinical models and activity in previous phase II trials. The purpose of our study is to asses activity and feasibility of the combination of D, O and C as first-line chemotherapy in MOC patients. Methods: MOC patients, with good ECOG performance status and chemonaive are eligible. Pts receive D 60 mg/m2 day 1, O 85 mg/m2 day 1 and oral C 650mg/m2 bid d1–14 every 3 weeks. Primary endpoints are response according to WHO criteria and toxiciy assesment according to NCI.CTCAE v3.0. Results: From November 2004 to December 2005, 17 Pts have been enrolled. Median ECOG PS is 1 (0–2) M/F:9/8. Median age is 57 years (38–68) Primary tumor are gastric carcinomas (82%) and lower oesofagus carcinomas (18%). Metastatic sites included peritoneum 58%, liver 23% and lung 23%. Median number of cycles is 5 (1–7) Treatment is well tolerated with no toxic deaths. NCI grade 3–4 toxicities include 2 Pts (11.8%) with grade 4 neutropenia and one of them developed septic shock; 2 Pts with grade 3 asthenia, 1 Pt with grade 3 vomiting and 1 patient with grade 3 neurotoxicity. Main NCI grade 2 toxicities are dhiarrea (35.3%) and neurotoxicity (23.5%). 13 Pts have been evaluated for response until now: 9 Pts have a confirmed Partial Response (69.2%) and 2 of them underwent salvage surgery; 3 Pts have Stabilized Disease and 1 Pt Progression Disease. Median time to progression and median overall survival have not been reached yet and the study is still ongoing. Conclusions: The combination of D, O and C at the dosses and schedule used in this trial is effective in MOC with a manageable toxicity profile No significant financial relationships to disclose.

Initial results of a phase II study of biweekly pemetrexed and gemcitabine in patients with advanced NSCLC

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7128-7128
Author(s):  
A. Dudek ◽  
T. Larson ◽  
M. McCleod ◽  
D. J. Schneider ◽  
J. E. Dowell ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Dose Intensity ◽  
Complete Response ◽  
Median Number ◽  
Median Dose ◽  
Ecog Performance Status ◽  
Response Data ◽  
Grade 3 ◽  
Ecog Ps

7128 Background: Pemetrexed (P), a multi-targeted antifolate, is synergisitic with gemcitabine (G) in preclinical models. A phase I study examining a biweekly schedule established a recommended phase 2 dose of G 1500 mg/m2 followed by P 500mg/m2. Methods: Patients with Stage IIIB (with pleural effusion) or IV NSCLC, ECOG PS of 0 or 1, no prior systemic chemotherapy, immunotherapy, or biological therapy were enrolled. G was infused over 30 minutes, followed immediately by P given intravenously over 10 minutes once on day 1 every 14 days. Cycles were repeated until 12 treatments or progressive disease. All patients received folic acid, vitamin B12 and steroid prophylaxis. Results: Data on 53 patients (29 male, 24 female) are currently available. Median age: 64 (range: 35, 80), ECOG performance status 0:1 = 38%:60%, Stage IIIB:IV = 19%:81%. Three hundred twelve cycles of treatment were administered with 14 dose reductions (26.4%); median number of doses was 5 for both G and P, and median dose intensity was 98.05% for both G and P. Response data included 1 complete response (1.9%), 14 partial responses (26.4%), 24 stable diseases (45.3%), and 10 progressive diseases (18.9%), with a response rate of 28.3% (95% CI: 16.8–42.3%). Patient-based Grade 3/4 hematologic events included febrile neutropenia (9.4%), neutropenia (28.3%), and thrombocytopenia (1.9%). Grade 3/4 non-hematologic events included fatigue (22.6%), dyspnea (7.5%), dehydration (7.5%), diarrhea (5.7%), constipation (3.8%), and pneumonia (1.9%). Preliminary median survival was 7.8 months (95% CI: 6.0–10.8) with 43.4% patients censored and median TTPD was 4.6 months (95% CI: 2.8–6.1). Conclusion: Biweekly G and P appear to be well tolerated in advanced NSCLC. A clinical benefit rate (ORR + SD) of 73.6% indicates activity in patients with advanced NSCLC. The dose intensity for biweekly G and P is higher than a previously reported 6-cycle, 21-day regimen with median dose intensity of 83.2% for P and 82.2% for G (West, et al. Proc ASCO 2005; 7117). [Table: see text]

Phase II multicenter study of chemotherapy (chemo)-naive castration-resistant prostate cancer (CRPC) not exposed to ketoconazole (keto), treated with abiraterone acetate (AA) plus prednisone

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5046-5046 ◽  
Author(s):  
C. Ryan ◽  
E. Efstathiou ◽  
M. Smith ◽  
M. Taplin ◽  
G. Bubley ◽  
...  
Keyword(s):  
Performance Status ◽  
Median Number ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Androgen Withdrawal ◽  
Psa Response ◽  
Grade 3 ◽  
Hormonal Therapies ◽  
Ecog Ps

5046 Background: AA is a potent inhibitor of the enzyme CYP17, a major contributor to androgen biosynthesis. Keto is also known to inhibit this enzyme but AA is many-fold stronger in its action. 33 pts with progressive metastatic disease, normal organ function, ECOG performance status (PS) 0–1, and no prior chemo were enrolled. Pts with prior keto treatment were excluded. AA (1000 mg qd) plus prednisone (5mg bid) were administered orally in 28 day cycles. Methods: Results: At baseline median age was 71.0 (range 52–85) yrs and median PSA was 24.7 (range 7.1–1110.0) ng/mL;19/26 pts (73%) had an ECOG PS of 0 and 7/26 (27%) had PS of 1; the median number of prior hormonal therapies was 2; all pts were on LHRHa and 73% of pts had received anti-androgen, all of whom had undergone prior anti-androgen withdrawal. Pts were evaluated at each cycle for PSA response according to PSAWG criteria. 27 pts have available data for PSA response. Total maximal PSA declines of ≥30%, ≥50%, ≥90% were observed in 89% (24/27), 85% (23/27) and 41% (11/27) pts, respectively. Week 12 PSA declines displayed a similar and sustained trend: ≥30%, ≥50% and ≥90% PSA decline in 82%, 78%, and 26% of pts. Post-treatment ECOG PS score was 0 in 24 (92%) pts: 19% experienced improvement in PS (PS 1 to 0 in 5 pts) and 19/19 pts maintained a PS of 0; Median time to PSA progression has not been reached. Majority of adverse events were grades 1–2. Incidence of hypokalemia - 12%; HTN - 6%; edema - 15%. One pt experienced a grade 3 drug-related HTN. Conclusions: Abiraterone acetate plus prednisone has significant anti-cancer activity in patients with metastatic CRPC not previously treated with ketoconazole or chemotherapy, as demonstrated by declines in PSA and improvement in performance status, and is well-tolerated. [Table: see text]

Treatment decision and outcome in mRCC patients with different ECOG performance status.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15553-e15553
Author(s):  
Ulrika Harmenberg ◽  
Kajsa Stenmo ◽  
Caroline De Flon ◽  
Peter Wersäll ◽  
Per Sandström
Keyword(s):  
Systemic Therapy ◽  
Performance Status ◽  
Treatment Decision ◽  
Outcome Data ◽  
Phase Iii ◽  
Targeted Agents ◽  
Ecog Performance Status ◽  
Clinical Registry ◽  
Treatment Line ◽  
Ecog Ps

e15553 Background: Phase III studies with targeted agents have shown improved survival for mRCC. There is limited outcome data for the whole mRCC patient group. We collect data in a clinical registry at Karolinska for all patients with mRCC in the Greater Stockholm Region since 2007. Here we present the relationship between ECOG performance status and treatment outcome in this population. Methods: Between 2007 and 2012, 273 patients with mRCC were included in the registry. Patients were divided in two groups: Those that were treated with targeted agents and non- treated patients (symptomatically treated). Results: ECOG PS, available for 63%, was lower for patients treated (n=127) compared to patients not treated with systemic therapy (n=46) (median 1 vs. 2. Median OS from diagnosis to death in respective group was 731 day (n=106) and 269 days (n=55). The median OS from date of first metastasis to death was 500 days and 176 days respectively. In the treated group median OS from start of systemic therapy to death was 321 days. There was a difference in median OS from start of systemic therapy to death between patients who received 1 (n=52)(A), 2 (n=32)(B), 3 (n=16)(C) or > 3 lines (n=6)(D) with a median OS of 160.5 days, 395 days, 641 days and 728.5 days respectively. Mean PS at first line treatment was 1.36 for patients who received only one line and ≤ 1 for patients who received several lines. 13/18 patients with ECOG PS 0 at 1st line received >1 line, corresponding numbers for PS 1, 2 and 3 at 1stline were 21/40, 3/14 and 0/4. The average/ medians ECOG PS at time for the last treatment line were 1.36/1 (A), 1.47/1 (B), 1.64/2 (C) and 1.67/2 (D). Median OS from start of systemic treatment to death was dependent on PS at the start of treatment, ECOG 0 (n=18) 622 days, 1 (n=40) 724 days, ECOG2 (n=14) 226 days, ECOG3 (n=4) 44 days. Irrespective of treatment line, patients with PS 0-1 at initiation of any line of therapy had a 55% chance (47/86) of receiving a subsequent line of treatment, while patients with PS 2-3 only had a 19% chance (7/37). Conclusions: Patients with a good performance status, ECOG 0-1 at treatment start, had longer OS and received more lines of treatment. Patients with ECOG PS 3 could in our hands not be treated at all with targeted agents.

Cetuximab plus 5-FU/FA/oxaliplatin (FOLFOX-4) versus FOLFOX-4 in the first-line treatment of metastatic colorectal cancer (mCRC): OPUS, a randomized phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4035-4035 ◽  
Author(s):  
C. Bokemeyer ◽  
I. Bondarenko ◽  
A. Makhson ◽  
J. T. Hartmann ◽  
J. Aparicio ◽  
...  
Keyword(s):  
Adverse Events ◽  
Performance Status ◽  
Controlled Study ◽  
Line Treatment ◽  
First Line ◽  
Ecog Performance Status ◽  
Curative Intent ◽  
Grade 3 ◽  
Ecog Ps ◽  
First Line Treatment

4035 Background: FOLFOX-4 is a standard first-line treatment for patients (pts) with mCRC. The IgG1 monoclonal antibody cetuximab has proven activity in combination with cytotoxic chemotherapy. Excellent response rates (RRs) have been reported with first-line cetuximab and FOLFOX-4. This randomized, controlled study was conducted to compare RRs of FOLFOX-4 + cetuximab vs FOLFOX-4. Methods: Pts with previously untreated epidermal growth factor receptor (EGFR)-expressing mCRC not resectable with curative intent were eligible. They were randomized 1:1, stratified by ECOG performance status (PS) (0–1 vs 2), to either Group A (cetuximab 400 mg/m2 initial dose then 250 mg/m2/week plus FOLFOX-4 every 2 weeks [oxaliplatin 85 mg/m2 day (d) 1; FA 200 mg/m2 d1, 2; 5-FU 400 mg/m2 bolus + 600 mg/m2 infusion over 22 h, d1, 2]) or Group B (FOLFOX-4 only). The primary objective was the best confirmed RR assessed by independent review; secondary objectives were progression- free survival (PFS), overall survival (OS), the R0 resection rate after metastatic surgery of curative intent and safety. Results: Between July 2005 and March 2006, 337 pts were randomized and treated in more than 70 centers in Europe. 181 (53.7%) pts were male; the median age of all pts was 61.0 years [24–82]; 305 (90.5%) pts had an ECOG PS of 0 or 1, and 32 (9.5%) of 2. The best overall confirmed RR was 45.6% in A and 35.7% in B. For pts with ECOG PS 0–1, RR was 49.0% in A and 36.8% in B (Odds Ratio 1.648, 95%CI [1.043- 2.604]). PFS and OS results are not yet available. The most common grade 3/4 adverse events were neutropenia (27.6% in A; 31.5% in B), diarrhea (7.1 and 6.0%), leucopenia (7.1 and 5.4%) and rash (9.4%, in A only). Conclusions: The addition of cetuximab increased the RR of FOLFOX-4 in first-line treatment of mCRC. Grade 3/4 adverse events, with the exception of skin rash, were not significantly more frequent in the cetuximab arm. No significant financial relationships to disclose.

A phase II study of capecitabine, irinotecan, and bevacizumab (XELIRI-A) in patients (pts) with previously untreated metastatic colorectal cancer (mCRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15019-e15019
Author(s):  
E. X. Chen ◽  
S. Welch ◽  
M. Krzyzanowska ◽  
H. MacKay ◽  
J. Knox ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Ecog Performance Status ◽  
Optimal Dosing ◽  
Open Label Phase ◽  
Dosing Strategies ◽  
Grade 3 ◽  
Ecog Ps

e15019 Background: Capecitabine (XEL), irinotecan (IRI) and bevacizumab (A) are all active agents in the treatment of mCRC. However, combining these agents has proven to be problematic due to overlapping toxicities. Optimal dosing strategies for this combination remain unclear. This study prospectively evaluated toxicity and efficacy of the XELIRI-A combination with dose modification. Methods: This was a single-institution, open-label phase II clinical trial. Eligible pts include those with previously untreated metastatic CRC, adequate organ function and ECOG performance status 0–2. IRI (200 mg / m2) and A (7.5 mg / kg) were given on day 1, and XEL (1000 mg / m2 p.o. BID) was given on days 1–14 of every 21-day cycle. The dose of XEL was reduced to 750 mg / m2 BID for pts age ≥ 65. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, time to progression, overall survival and toxicity. Results: 50 pts (ECOG PS 0:1 = 27:23; male:female= 34:16) were enrolled over 19 months. Median age was 58 (range: 35–72). 7 pts had prior adjuvant chemotherapy. A total of 360 cycles were administered, with a median of 6 (range: 1–16). To date, 20 confirmed PR, 3 unconfirmed PR, and 20 SD by RECIST criteria were observed (ORR= 40%, disease control rate 86%). The median PFS was 11.1 months (95% CI: 9.2 months - not reached), and the 1-year progression-free rate was 49%. 7 pts have gone on to have metastatectomy. The most frequently reported related grade 3 or 4 adverse events were neutropenia (6), hand-foot syndrome (6), and diarrhea (5). One death was seen on study, and 1 pt had treatment-emergent grade 3 hypertension. Conclusions: XELIRI-A at doses studied appears to be well- tolerated. Results are favorable compared to those from previous studies. XELIRI-A at reduced doses is safe and effective as first-line treatment for mCRC. [Table: see text]

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