Dataset Information

Health-related quality of life in patients with metastatic colorectal cancer treated with panitumumab in first- or second-line treatment.

ABSTRACT:

Background

Panitumumab in combination with chemotherapy was evaluated in two pivotal clinical trials in first- and second-line treatment of metastatic colorectal cancer (mCRC), respectively. This analysis compared the health-related quality of life (HRQoL) of patients with or without panitumumab in the two trials.

Methods

Patients with mCRC were randomised to FOLFOX (first-line trial) or FOLFIRI (second-line trial)±panitumumab. The EuroQoL 5-Dimensions Health State Index (EQ-5D HSI) and Visual Analogue Scale (EQ-5D VAS) were assessed at baseline and monthly follow-up until disease progression. Patients with wild-type KRAS mCRC with baseline and post-baseline HRQoL scores were included. Difference in change from baseline between treatment groups was evaluated using linear mixed and pattern-mixture models.

Results

In the first-line trial, 576 patients with wild-type KRAS mCRC (284 panitumumab+FOLFOX4 and 292 FOLFOX4 alone) were included in the HRQoL analyses. In the second-line trial, 530 patients with wild-type KRAS mCRC were included in these analyses (263 panitumumab+FOLFIRI and 267 FOLFIRI alone). There was no significant difference in the change in EQ-5D HSI and VAS scores between treatment groups in either trial.

Conclusion

The addition of panitumumab to FOLFOX4 or FOLFIRI in first- or second-line treatment of wild-type KRAS mCRC significantly improved progression-free survival without compromising HRQoL.

SUBMITTER: Bennett L

PROVIDER: S-EPMC3242525 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Publications

Health-related quality of life in patients with metastatic colorectal cancer treated with panitumumab in first- or second-line treatment.

Bennett L L Zhao Z Z Barber B B Zhou X X Peeters M M Zhang J J Xu F F Wiezorek J J Douillard J-Y JY

British journal of cancer 20111011 10

<h4>Background</h4>Panitumumab in combination with chemotherapy was evaluated in two pivotal clinical trials in first- and second-line treatment of metastatic colorectal cancer (mCRC), respectively. This analysis compared the health-related quality of life (HRQoL) of patients with or without panitumumab in the two trials.<h4>Methods</h4>Patients with mCRC were randomised to FOLFOX (first-line trial) or FOLFIRI (second-line trial)±panitumumab. The EuroQoL 5-Dimensions Health State Index (EQ-5D HS ...[more]

PMID: 21989186

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Project description:IntroductionMetastatic colorectal cancer is rarely curable. Improving quality of life is therefore a key treatment goal. We report quality of life for patients with RAS wild-type metastatic colorectal cancer in the PRIME study.MethodsA randomised phase 3 open-label study of first-line panitumumab+FOLFOX4 vs FOLFOX4 enrolled adults with untreated metastatic colorectal cancer and an Eastern Cooperative Oncology Group performance status of 0-2. This analysis includes patients with wild-type RAS tumours (n=505). Quality of life (prespecified end point) was assessed using the EuroQoL 5-domain health state index and overall health rating in all patients and by early tumour shrinkage status (≥30% reduction in size by week 8; exploratory end point). Differences in quality of life were assessed using analysis of covariance and a mixed-effect piecewise linear model, and were also analysed by skin toxicity severity.ResultsThere were no statistically significant differences between treatment arms from baseline to progression or to discontinuation. Grade 3+ skin toxicity was reported by 38% of patients receiving panitumumab+FOLFOX4 and 2% receiving FOLFOX4 alone. There were no significant differences in quality of life between patients with grade 0-2 skin toxicity and those with grade 3+ skin toxicity. More patients receiving panitumumab+FOLFOX4 vs FOLFOX4 had early tumour shrinkage (p<.001). In patients with tumour symptoms at baseline, there were statistically significant improvements in quality of life in those with early tumour shrinkage versus those without early tumour shrinkage.ConclusionsAddition of panitumumab to FOLFOX4 in first-line therapy for metastatic colorectal cancer prolongs survival and has no negative effect on overall quality of life compared with FOLFOX4 alone. Specific quality of life assessments for skin toxicity should be included in study designs to better define the direct effect of these adverse events.Trial registration numberNCT00364013.

Project description:BackgroundIntegument-related toxicities are common during epidermal growth factor receptor (EGFR)-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT) KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial.MethodsIntegument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity.Results154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59); most (98%) experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]). Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56%) compared with those with grade 0/1 (29%). Mean overall EQ-5D health state index scores (0.81 vs. 0.78), health rating scores (72.5 vs. 71.0) and QLQ-C30 global health status scores (65.8 vs. 66.7) were comparable at baseline vs. safety follow-up (8 weeks after completion), respectively and appeared unaffected by skin toxicity severity.ConclusionsFirst-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument-related toxicity.Trial registrationClinicalTrials.gov NCT00508404.

Project description:Introduction: In Saudi Arabia, patients with metastatic colorectal cancer (mCRC) with wild-type RAS mutations may be treated with either cetuximab plus chemotherapy (CET + CT) or panitumumab plus chemotherapy (PAN + CT), which are epidermal growth factor receptor (EGFR) antibodies. This study calculated the costs of adverse event (AE) management linked to anti-EGFR treatment in Saudi Arabia's national health budget from payer and societal perspectives. Methods: An adaptation of a global model developed in Microsoft Excel® was performed to estimate the costs of AE management associated with the first-line treatment (CET + CT and PAN + CT) of RAS wild-type mCRC patients in Saudi healthcare settings. The frequencies of common and highly common AEs were sourced from the summaries of product characteristics of CET and PAN, whereas AE severity was captured from a meta-analysis. Unit costs in Saudi Riyal (SAR) were obtained from the National Guard of Health Affairs and Ministry of Health 2024 price lists. The model assumptions, inputs, and results were validated using a local Delphi panel. Results: Within the Saudi payer perspective model, treatment with CET + CT vs PAN + CT resulted in average population cost savings of SAR 9 246 133 (4 741 606 international dollars [Intl ])andper-patientcostsavingsofSAR20 321(Intl 10 421) for severe AEs, and average population cost savings of SAR 16 039 427 (Intl 8 225 347)andper-patientcostsavingsofSAR35 251(Intl 18 077) for all-grade AEs. On the other hand, within the Saudi societal perspective model, treatment with CET + CT vs PAN + CT resulted in average population cost savings of SAR 11 386 314 (Intl 5 839 135)andper-patientcostsavingsofSAR25 025(Intl 12 833) for severe AEs, while resulting in average population cost savings of SAR 18 179 608 (Intl 9 322 875)andperpatientcostsavingsofSAR39 955(Intl 20 489) for all grade AEs. Conclusion: The CET + CT regimen was associated with a lower AE frequency than the PAN + CT regimen for the treatment of untreated RAS wild-type mCRC patients, thus resulting in AE management cost savings from both the Saudi payer and societal perspectives. These substantial cost savings may mitigate the financial burden of mCRC in Saudi healthcare settings.

Project description:ImportanceMetastatic colorectal cancer (mCRC) with deficient DNA mismatch repair (dMMR) shows frequent and durable responses to programmed cell death 1 blockade. While most of these tumors are sporadic and observed in older patients, first-line pembrolizumab data are limited to findings from the KEYNOTE-177 trial (A Phase III Study of Pembrolizumab [MK-3475] vs Chemotherapy in Microsatellite Instability-High [MSI-H] or Mismatch Repair Deficient [dMMR] Stage IV Colorectal Carcinoma).ObjectiveTo investigate outcome with first-line pembrolizumab monotherapy in mostly older patients with dMMR mCRC at a multisite clinical practice.Design, setting, and participantsThis cohort study included consecutive patients with dMMR mCRC who received pembrolizumab monotherapy between April 1, 2015, and January 1, 2022, at Mayo Clinic sites and the Mayo Clinic Health System. Patients were identified from review of electronic health records at the sites, which included the evaluation of digitized radiologic imaging studies.InterventionPatients with dMMR mCRC received first-line pembrolizumab, 200 mg, every 3 weeks.Main outcomes and measuresThe primary study end point was progression-free survival (PFS), which was analyzed using the Kaplan-Meier method and a multivariable stepwise Cox proportional hazards regression model. Clinicopathological features, including metastatic site and molecular data (BRAF V600E and KRAS), were also analyzed along with tumor response rate, which was determined using Response Evaluation Criteria in Solid Tumors, version 1.1.ResultsThe study cohort included 41 patients (median [IQR] age at treatment initiation, 81 [76-86] years; 29 females [71%]) with dMMR mCRC. Of these patients, 30 (79%) had the BRAF V600E variant and 32 (80%) were classified as having sporadic tumors. Median (range) follow-up was 23 (3-89) months. Median (IQR) number of treatment cycles was 9 (4-20). Overall response rate was 49% (20 of 41 patients), including 13 patients (32%) with complete responses and 7 (17%) with partial responses. Median (IQR) PFS was 21 (95% CI, 6-39) months. Liver as a site of metastasis was associated with significantly poorer PFS vs nonliver metastasis (adjusted hazard ratio, 3.40; 95% CI, 1.27-9.13; adjusted P = .01). Complete and partial responses were observed in 3 patients (21%) with liver metastasis vs 17 patients (63%) with nonliver metastases. Treatment-related grade 3 or 4 adverse events were observed in 8 patients (20%), 2 of whom discontinued therapy; there was 1 treatment-related death.Conclusions and relevanceThis cohort study found a clinically significant prolongation of survival in older patients with dMMR mCRC who were treated with first-line pembrolizumab in routine clinical practice. Furthermore, liver vs nonliver metastasis was associated with poorer survival in this patient population, which suggests that the metastatic site has implications for survival outcome.

Project description:BackgroundFew data are available regarding the treatment of metastatic colorectal cancer elderly patients with anti-EGFR agents in combination with chemotherapy. FOLFOX plus panitumumab is a standard first-line option for RAS wild-type metastatic colorectal cancer. Slight adjustments in chemo-dosage are commonly applied in clinical practice to elderly patients, but those modified schedules have never been prospectively tested. Clinical definition of elderly (≥70 years old) patients that may deserve a more or less intensive combination therapy is still debated. Several geriatric screening tools have been developed to predict survival and risk of toxicity from treatment. Among those, the G8 screening tool has been tested in cancer patients showing the strongest prognostic value for overall survival, while the CRASH score can stratify patients according to an estimated risk of treatment-related toxicities.MethodsThe PANDA study is a prospective, open-label, multicenter, randomized phase II trial of first-line therapy with panitumumab in combination with dose-adjusted FOLFOX or with 5-fluorouracil monotherapy, in previously untreated elderly patients (≥70 years) with RAS and BRAF wild-type unresectable metastatic colorectal cancer. RAS and BRAF analyses are centralized. Geriatric assessment by means of G8 and CRASH score is planned at baseline and G8 will be re-evaluated at disease progression. The primary endpoint is duration of progression-free survival in both arms. Secondary endpoints include prospective evaluation of the prognostic role of G8 score and the correlation of CRASH risk categories with toxicity.DiscussionThe PANDA study aims at exploring safety and efficacy of panitumumab in combination with FOLFOX or with 5FU/LV in elderly patients affected by RAS and BRAF wild-type metastatic colorectal cancer, to identify the most promising treatment strategy in this setting. Additionally, this is the first trial in which the prognostic role of the G8 score will be prospectively evaluated. Results of this study will drive further experimental developments for one or both combinations.Trial registrationPANDA is registered at Clinicaltrials.gov : NCT02904031 , July 11, 2016. PANDA is registered at EudraCT-No.: 2015-003888-10, September 3, 2015.

Dataset Information

Health-related quality of life in patients with metastatic colorectal cancer treated with panitumumab in first- or second-line treatment.

Background

Methods

Results

Conclusion

Publications

Health-related quality of life in patients with metastatic colorectal cancer treated with panitumumab in first- or second-line treatment.

Similar Datasets

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