Clinical practice use of panitumumab combined with chemotherapy in patients with wild-type RAS metastatic colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 852-852
Author(s):  
Holger Frithjof Hebart ◽  
Jiri Tomasek ◽  
Tibor Csõszi ◽  
Reija Koukakis ◽  
George Kafatos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Practice ◽  
Metastatic Colorectal Cancer ◽  
Overall Response Rate ◽  
Skin Toxicity ◽  
Wild Type ◽  
Response Data ◽  
Randomized Controlled ◽  
Study Results ◽  
Anticancer Treatment

852 Background: This study aimed to understand panitumumab (pmab) use in clinical practice for patients with wild-type RAS metastatic colorectal cancer (mCRC), in first-line (1L) with FOLFOX or second-line (2L) with FOLFIRI following fluoropyrimidine-based chemotherapy (excl. irinotecan). Methods: This is a combined analysis of two observational, non-interventional prospective cohort studies conducted in Germany/France (2012-2016) and Bulgaria/Czech Republic/Hungary (2013-2016). Results: Results are presented in the order of 1L FOLFOX (n = 332) followed by 2L FOLFIRI (n = 94). Patients received a median of 10 and 11.5 pmab infusions. The median duration of pmab exposure was 5.7 and 6.9 months (note that 53 and 10 patients continued pmab use after study end). The unadjusted overall response rate (complete or partial response) was 42% and 29%, based on 45% and 44% of patients with available response data post-baseline. In the 1L setting, resectability was achieved in 9%, not achieved in 42%, and unknown in 48%. Hospitalizations were reported for 100% and 99%, mostly cancer-related visits such as scheduled anticancer treatment (e.g. chemotherapy/pmab administrations), tumor assessment visits, or interventions; 93% in both groups reported outpatient, 66% and 60% inpatient visits. Conclusions: Overall, the study results show that treatment patterns and clinical efficacy of pmab in routine clinical practice were comparable to randomized controlled trials (RCTs). The ADR/SADR skin toxicity events are lower than expected based on findings from RCTs, however, similar findings have been shown in a previous observational study. More investigation is required to understand the reason for this.[Table: see text]

Liquid biopsy-driven anti-EGFR rechallenge in patients with metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3577-3577
Author(s):  
Stefano Mariani ◽  
Marco Puzzoni ◽  
Nicole Liscia ◽  
Valentino Impera ◽  
Andrea Pretta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Practice ◽  
Metastatic Colorectal Cancer ◽  
Liquid Biopsy ◽  
Selection Criteria ◽  
Wild Type ◽  
Braf Mutations ◽  
Previous Response ◽  
Clinical Variables ◽  
Ct Dna

3577 Background: The rechallenge with EGFR inhibitors represents an emerging strategy for anti-EGFR pre-treated patients with RAS wild type colorectal cancer (CRC). Unfortunately definitive selection criteria for anti-EGFR rechallenge in this setting are lacking. Very recently RAS wild type status on circulating tumor DNA (ct-DNA) at the time of rechallenge along with already known clinical criteria emerged as a potential watershed for this strategy. In the present study we explored liquid biopsy-driven anti-EGFR rechallenge strategy in the clinical practice for patients with metastatic colorectal cancer. Methods: Ct-DNA from RAS and BRAF wild type metastatic CRC patients previously treated with an anti-EGFR containing therapy was analyzed for RAS/BRAF mutations with the aim to evaluate the rechallenge strategy with anti-EGFR. The ct-DNA was analyzed for RAS-BRAF mutations using pyro-sequencing (PyroMark Q24 MDx Workstation) and nucleotide sequencing (Genetic Analyzer ABI3130) assays. Real-time PCR (Idylla) and droplet digital PCR (QX200 System) were performed to confirm the RAS-BRAF mutation status. Several clinical variables including previous response to anti EGFR containing therapy, tumor sidedness and anti-EGFR free interval were evaluated in relation to outcome. Tumor response evaluation was performed according to RECIST 1.1. Differences between categorical variables were evaluated using the Fisher’s exact test. Survival probability over time was estimated by the Kaplan–Meier method. Significant differences in the probability of survival between the strata were evaluated by log-rank test. Results: Twenty patients were included in the study. All patients were tested for RAS-BRAF mutations in ct-DNA. Fourteen patients (70%) showed a RAS-BRAF WT molecular profile, six patients (30%) showed a KRAS mutation. All the patients with ct-DNA RAS-BRAF WT profile underwent rechallenge with anti-EGFR. In details 11 patients (78.6%) underwent irinotecan+ cetuximab treatment, whereas 3 patients (21.4%) underwent panitumumab monotherapy. As for the outcome results to the rechallenge strategy, the median OS was 7 months (95% CI 5.0 to 13.0), the median PFS was 3 months (95% CI 2.0 to 6.0), the ORR was 27.3% with a DCR of 54.5%. Among the clinical variables evaluated as putative predictive/prognostic factors, previous response to anti-EGFR treatment was related to a not statistically significant improved OS (12 months vs 5 months HR:0.19 p: 0.06) and to a statistically significant improved ORR (75% vs 0% p:0.03). Conclusions: The rechallenge strategy with anti-EGFR confirmed to be feasible in clinical practice. The clinical outcome resulted consistent with the literature data. In addition to the molecular selection through the analysis of ct-DNA for RAS, previous response to anti EGFR treatment is confirmed as a prospective selection criteria for this therapeutic option.

Tumor bulk as a prognostic biomarker and predictor of benefit from anti-EGFR therapy in patients with metastatic colorectal cancer: Analysis of 476 patients from the ARCAD Clinical Trials Program.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 108-108
Author(s):  
Benjamin Adam Weinberg ◽  
Manel Rakez ◽  
Benoist Chibaudel ◽  
Tim Maughan ◽  
Richard Adams ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Lung Metastases ◽  
Performance Status ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Wild Type ◽  
Cox Models ◽  
Study Results

108 Background: Primary tumor sidedness has emerged as a prognostic and predictive biomarker for patients (pts) with metastatic colorectal cancer (mCRC). Tumor bulk has also been postulated to predict response to anti-EGFR therapy. We sought to evaluate the role of tumor bulk as a predictive biomarker to anti-EGFR therapy in pts with left- (LS) and right-sided (RS) mCRC. Methods: Data from 476 pts with mCRC enrolled across 2 first-line trials of anti-EGFR plus chemotherapy versus chemotherapy were pooled. Pts were included if there was available information on tumor sidedness and tumor bulk. All were KRAS wild-type and BRAF wild-type or unknown BRAF status. The right colon was defined as the cecum through the transverse colon, and the left colon as the splenic flexure through the rectum. Tumor bulk was the mean tumor size of target lesions at baseline, bulky defined as > 3.5 cm. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for performance status (PS), platelet count, primary tumor (PT) resection, number of metastatic sites, and stratified by study. Results: Pts with bulky tumors (211, 44%) had higher PS, white blood cell and platelet counts, higher CEA, fewer sites of metastatic disease, more liver than lung metastases, and fewer had PT resection. OS and PFS medians in months (mos) are presented in the table with 95% confidence intervals (95%CIs). Bulky tumors had inferior median OS compared with non-bulky (mOS, 17.9 vs. 21.3 mos, HRadj 1.33, 95% CI 1.05-1.69, P = 0.016) although median PFS was similar (mPFS, 8.6 vs. 8.7 mos, HRadj 1.15, 95% CI 0.92-1.42, P = 0.21). Conclusions: Tumor bulk is an independent prognostic factor for OS in KRAS wild-type and BRAF wild-type or unknown BRAF status pts. Pts with non-bulky RS tumors have survival outcomes similar to pts with bulky LS tumors. Although the mPFS for pts with RS tumors treated with anti-EGFR therapy was the lowest across subgroups, this finding was not statistically significant. Further research is warranted into whether pts with bulky RS tumors benefit from anti-EGFR therapy. Clinical trial information: NCT00182715, NCT00640081. [Table: see text]

Clinical benefit rate (CBR) of panitumumab monotherapy among patients with KRAS wild-type metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14176-e14176
Author(s):  
Hagen F. Kennecke ◽  
Howard John Lim ◽  
Balvindar Singh Johal ◽  
Muhammad Zulfiqar ◽  
Caroline Speers
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Endpoint ◽  
Clinical Benefit ◽  
Single Agent ◽  
Wild Type ◽  
Clinical Benefit Rate ◽  
Previous Therapy ◽  
Study Results ◽  
Third Line

e14176 Background: Panitumumab (Pmab) improves progression free survival as first-, second- and third-line therapy for KRAS wild-type (wt) metastatic colorectal cancer (mCRC). Only in the third-line setting is there evidence of benefit of Pmab monotherapy. In this analysis of an exploratory biomarker study of Pmab monotherapy, the clinical benefit rate of Pmab according to previous lines of therapy is described. Methods: Patients (pts) with KRAS non-mutated, measurable MCRC previously treated with or ineligible for oxaliplatin/5-FU and irinotecan were treated with Pmab 6mg/kg IV q2w until progression or toxicity. The primary endpoint is clinical benefit rate (complete (CR) or partial response (PR) + prolonged stable disease (PSD) > = 24 weeks) by RECIST criteria. Results: The study completed accrual and (40) evaluable patients were treated between September 2009 and December 2011 of which 32 were evaluable for the primary endpoint. Median follow-up was 8.8 months, median age was 64.5 years and 90% were ECOG 0/1. Previous therapy was: 5-FU/Capecitabine(C) only in 12 pts, Irinotecan/5-FU/C only in 2 patients, Oxaliplatin/5-FU/C only in 3 pts, Oxaliplatin/Irinotecan/5-FU/C in 23 pts. 22 patients received prior Bevacizumab. Median number of cycles was 8 and 6 pts required a dose modification. There were 7 (22%) PRs and 7 (22%) pts experienced PSD >=24 weeks. Clinical benefit rate (PR+PSD) according to previous therapy was 33% (3/9) for 5FU/C only, 100% (2/2) Oxaliplatin/FU/C only, 0% (0/2) Irinotecan/FU/C only, and 47% (9/19) for Oxaliplatin/Irinotecan/5FU/C. Conclusions: Pmab monotherapy is well tolerated and response rates vary according to previous lines of therapy. Patients ineligible for irinotecan and/or oxaliplatin experience a high clinical benefit rate with single agent Panitumumab and should be considered for such therapy. Updated study results will be presented.

scholarly journals Safety and Effectiveness of Aflibercept + Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) for the Treatment of Patients with Metastatic Colorectal Cancer (mCRC) in Current Clinical Practice: OZONE Study

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 657 ◽  
Author(s):  
Ian Chau ◽  
Marwan Fakih ◽  
Pilar García-Alfonso ◽  
Zdenĕk Linke ◽  
Ana Ruiz Casado ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Practice ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Anticancer Therapy ◽  
Current Clinical Practice ◽  
Study Results ◽  
Grade 3

For patients with metastatic colorectal cancer (mCRC) that have failed a first-line oxaliplatin-based regimen, the preferred treatment option is an irinotecan-based regimen. This prospective, observational, noncomparative, post-authorization safety study (OZONE) evaluated the safety and effectiveness of aflibercept plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) in patients with mCRC treated in daily practice after failure of an oxaliplatin-based regimen. Patients were grouped by age, renal impairment, hepatic impairment, race, number, and type of prior anticancer therapy. Of 766 treated patients enrolled, 59.5% were male, 94.8% had an Eastern Cooperative Oncology Group performance status of 0–1, all received previous chemotherapy (97.8% including oxaliplatin), and 58.6% had prior exposure to bevacizumab. At least one grade ≥ 3 treatment-emergent adverse event (TEAE) was reported in 68.3% of patients. Neutropenia, hypertension, diarrhea, and asthenia were the most frequently occurring grade ≥ 3 TEAEs. Antivascular endothelial growth factor class events were infrequent. Subgroup analyses did not reveal major differences in the safety profile according to age, renal and hepatic status, race, or prior anticancer therapy. For the total population, median overall survival was 12.5 months, median progression-free survival was 6.1 months, and overall response rate was 16.3%. Aflibercept in combination with FOLFIRI is a safe and efficacious regimen administered in current clinical practice to patients with mCRC previously treated with oxaliplatin. The study results, conducted in real-world clinical practice with a less selected patient population, are aligned with the VELOUR (NCT00561470) trial and no new safety issues were identified.

Real-world costs of cetuximab + chemotherapy administered every two weeks versus weekly for treatment of metastatic colorectal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 22-22 ◽  
Author(s):  
Chris Pescott ◽  
Michael Batech ◽  
Emmanuelle Boutmy ◽  
Philippe Ronga ◽  
Francois-Xavier Lamy
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Linear Models ◽  
Skin Toxicity ◽  
Exposure Period ◽  
Wild Type ◽  
Inverse Probability ◽  
Gamma Distributions ◽  
Effective Cost ◽  
Cost Differences

22 Background: Cetuximab (CET) 250 mg/m2 weekly (q1w) after an initial dose of 400 mg/m2 added to chemotherapy (CT) is licensed for treatment of (K)RAS wild-type metastatic colorectal cancer (mCRC). In practice, administration of CET 500 mg/m2 plus CT every 2 weeks (q2w) is common. We compared healthcare costs between q2w and q1w regimens in a US claims database study. Methods: A cohort of 2,943 mCRC patients CET-treated between 2010 and 2016, identified in IBM MarketScan, was analyzed for costs associated with CET+CT q2w vs q1w. All-category costs (ACC), stratified by overall outpatient (OO), inpatient (OI), and pharmacy (OP) claimed costs during the exposure period, were compared between groups. Additionally, subcategories of CRC- and skin toxicity (ST)–related claims were explored, and imputation of capitated claim costs was performed. Patients were weighted by the stabilized inverse probability of treatment (IPTW) based on a high-dimensional propensity score to control for confounding. Generalized linear models (GLMs) with gamma distributions were used to compare regimens. Inflation-adjusted costs (2016 US dollars) are presented per patient per month ($PPPM) with 95% CIs. Results: 1,779 and 951 patients were classified as q1w and q2w, respectively. Median ACC were 14,089 (q2w) vs 14,034 (q1w) $PPPM. Mean ACC and OO, OI, and OP costs are summarized in the table. CIs overlapped in each category, with GLMs showing no statistically significant differences. This finding was similar for CRC and ST subcategories. Conclusions: No cost differences were found between q2w and q1w regimens. In line with published noninferiority of overall survival with the q2w regimen, it represents an effective, cost-neutral option for treating mCRC patients. [Table: see text]

Cetuximab Plus Various Chemotherapy Regimens for Patients with KRAS Wild-Type Metastatic Colorectal Cancer

Chemotherapy ◽  
2015 ◽  
Vol 61 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Payam Azadeh ◽  
Nafiseh Mortazavi ◽  
Arezoo Tahmasebi ◽  
Farnaz Hosseini Kamal ◽  
Kambiz Novin
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
The Other ◽  
Hematologic Toxicity ◽  
Wild Type ◽  
Standard Chemotherapy ◽  
Free Survival

Background: The aim of this study was to compare the efficacy and hematologic toxicity of cetuximab combined with various types of chemotherapy regimens in patients with KRAS wild-type metastatic colorectal cancer (mCRC). Methods: The response rate, progression-free survival (PFS) and overall survival of the patients were analyzed. Results: In total, 45 patients were included in the study. The overall response rate for the combination of cetuximab and FOLFOX, FOLFIRI and CAPOX was 20, 46 and 30%, respectively, but the differences were not statistically significant. The median PFS for the three groups were 8, 6 and 3.5 months, respectively, but again these differences were not significant. All-grade leukopenia and anemia for the cetuximab plus FOLFOX group were significantly higher than for the other chemotherapy regimens. Conclusion: Our findings suggest that the combination of cetuximab and the three standard chemotherapy regimens resulted in the same outcomes in our patient population of mCRC, with higher hematologic toxicities among the FOLFOX subgroup.

scholarly journals Randomized controlled trial on the skin toxicity of panitumumab in Japanese patients with metastatic colorectal cancer: HGCSG1001 study; J-STEPP

2015 ◽  
Vol 11 (4) ◽  
pp. 617-627 ◽  
Author(s):  
Yoshimitsu Kobayashi ◽  
Yoshito Komatsu ◽  
Satoshi Yuki ◽  
Hiraku Fukushima ◽  
Takahide Sasaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Randomized Controlled Trial ◽  
Metastatic Colorectal Cancer ◽  
Controlled Trial ◽  
Skin Toxicity ◽  
Japanese Patients ◽  
Randomized Controlled

Randomized controlled trial on the skin toxicity of panitumumab in third-line treatment of KRAS wild-type metastatic colorectal cancer: HGCSG1001 (Japanese Skin Toxicity Evaluation Protocol with Panitumumab; J-STEPP).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 541-541
Author(s):  
Ichiro Iwanaga ◽  
Yoshito Komatsu ◽  
Satoshi Yuki ◽  
Yoshimitsu Kobayashi ◽  
Naoya Sakamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Group ◽  
Metastatic Colorectal Cancer ◽  
Treatment Period ◽  
Human Monoclonal Antibody ◽  
Skin Toxicity ◽  
Japanese Patients ◽  
Reactive Group ◽  
Randomized Controlled ◽  
Third Line

541 Background: Panitumumab (Pmab), a fully human monoclonal antibody targeting the EGFR, has been demonstrated the efficacy in patients with KRASwild-type metastatic colorectal cancer (mCRC). Though STEPP study (Lacouture et al, JCO 2010) showed that pre-emptive skin treatment reduced skin toxicities compared with reactive treatment among patients receiving Pmab, the data of Asians has not been reported. We planned a randomized controlled open-label trial to verify the differences between pre-emptive and reactive treatment for skin toxicities in Japanese patients. Methods: Patients receiving Pmab-containing treatments as third line regimen for mCRC were randomly assigned 1:1 to pre-emptive or reactive skin treatment group. In the pre-emptive treatment group, patients received skin moisturizers, sunscreen, topical steroid and minocycline. In the reactive treatment group, patients received only skin moisturizers. The primary endpoint was the cumulative incidence of ≥ grade 2 skin toxicities during the 6-week treatment period. Retrospectively, dermatologist reviewed skin toxicities with photographs in blinded manner. Results: Out of 95 enrolled patients, 47 patients were randomly assigned to pre-emptive group, and 48 to reactive group. The incidence of ≥ grade 2 skin toxicities during the 6-week treatment period (according to investigator’s assessment) was 21.3% and 62.5% (risk ratio [RR] = 0.34, 95% CI 0.19 - 0.62; p<0.001) for the pre-emptive and reactive treatment groups, respectively. A similar trend was observed in central review by dermatologist (18.6% and 50.0%, respectively [RR = 0.37, 95% CI 0.19 - 0.74; p = 0.002]). The concordance rate between them was 75.8%. Median time to first occurrence of ≥ grade 2 skin toxicities was not reached in the pre-emptive group and 3.2 weeks (95% CI 1.9 - 6.1) in reactive group (p < 0.001). Conclusions: The pre-emptive skin treatment could reduce the severity of the skin toxicities during the Pmab treatment. Our data clearly validate that the pre-emptive treatment is also recommended in Japanese patients. Clinical trial information: 000004883.

Sequential Versus Combination Therapy of Metastatic Colorectal Cancer Using Fluoropyrimidines, Irinotecan, and Bevacizumab: A Randomized, Controlled Study—XELAVIRI (AIO KRK0110)

2019 ◽  
Vol 37 (1) ◽  
pp. 22-32 ◽  
Author(s):  
Dominik Paul Modest ◽  
Ludwig Fischer von Weikersthal ◽  
Thomas Decker ◽  
Ursula Vehling-Kaiser ◽  
Jens Uhlig ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Combination Therapy ◽  
Metastatic Colorectal Cancer ◽  
Combination Chemotherapy ◽  
Cox Model ◽  
Phase Iii ◽  
Controlled Study ◽  
Wild Type ◽  
Randomized Controlled ◽  
Ras Status

Purpose The XELAVIRI trial investigated the optimal treatment strategy for patients with untreated metastatic colorectal cancer. We tested the noninferiority of initial treatment with a fluoropyrimidine plus bevacizumab, followed by the addition of irinotecan at first progression (arm A) versus upfront use of fluoropyrimidine plus irinotecan plus bevacizumab (arm B) in a 1:1 randomized, controlled phase III trial. Methods The primary efficacy end point was time to failure of the strategy (TFS). Given a 90% CI, a power of 70%, and a one-sided α of .05, the margin for noninferiority was set at 0.8. In the case of demonstrated noninferiority of TFS, an analysis of symptomatic toxicities during TFS would define the superior strategy. Secondary end points included the effect of molecular subgroups on efficacy parameters. Results A total of 421 randomly assigned patients (arm A: n = 212; arm B: n = 209) formed the full analysis set. Median age was 71 and 69 years, respectively. Noninferiority of TFS was not shown (hazard ratio [HR], 0.86; 90% CI, 0.73 to 1.02). In detail, patients with RAS/BRAF wild-type tumors benefitted from combination chemotherapy (HR, 0.61; 90% CI, 0.46 to 0.82; P = .005), whereas patients with RAS mutant tumors (HR, 1.09; 90% CI, 0.81 to 1.46; P = .58) did not (Cox model for interaction of study arm and RAS status: P = .03). Comparable results were obtained for overall survival. Conclusion Noninferiority of sequential escalation therapy compared with initial combination chemotherapy could not be demonstrated for TFS. RAS status may be important to guide therapy as treatment of patients with upfront combination therapy was clearly superior in RAS/BRAF wild-type tumors, whereas sequential escalation chemotherapy seems to provide comparable results in patients with RAS mutant tumors.

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