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Radiotherapy and Oncology : Journal of... Sep 2023Standard treatment of squamous cell carcinoma of the anus (SCCA)is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase II study...
BACKGROUND AND PURPOSE
Standard treatment of squamous cell carcinoma of the anus (SCCA)is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase II study (EudraCT: 2011-005436-26) assessed the tolerance and complete response (CR) rate at 8 weeks of panitumumab (Pmab) combined with MMC-5FU-based CRT.
METHODS
Patients with locally advanced tumors without metastases (T2 > 3 cm, T3-T4, or N + whatever T stage) were treated with IMRT up to 65 Gy and concomitant CT according to the doses defined by a previous phase I study (MMC: 10 mg/m; 5FU: 400 mg/m; Pmab: 3 mg/kg). The expected CR rate was 80%.
RESULTS
Forty-five patients (male: 9, female: 36; median age: 60.1 [41.5-81]) were enrolled in 15 French centers. The most common related grade 3-4 toxicities observed were digestive (51.1%), hematologic (lymphopenia: 73.4%; neutropenia: 11.1%), radiation dermatitis (13.3%), and asthenia (11.1%) with RT interruption in 14 patients. One patient died because of mesenteric ischemia during the CRT, possibly related to treatment. In ITT analysis, the CR rate at 8 weeks after CRT was 66.7% [90%CI: 53.4-78.2]. Median follow-up was 43.6 months [IC 95%: 38.61-47.01]. Overall survival, recurrence-free and colostomy-free survival at 3 years were 80% [95%CI: 65.1-89], 62.2% [IC95%: 46.5-74.6] and 68.8 % [IC95%: 53.1-80.2] respectively.
CONCLUSION
Panitumumab in combination with CRT for locally advanced SCCA failed to meet the expected CR rate and exhibited a poor tolerance. Furthermore, late RFS, CFS, and OS did not suggest any outcome improvement to justify further clinical trials.
CLINICALTRIALS
gov identifier: NCT01581840.
Topics: Humans; Male; Female; Middle Aged; Anal Canal; Panitumumab; Anus Neoplasms; Chemoradiotherapy; Fluorouracil; Mitomycin; Antineoplastic Combined Chemotherapy Protocols; Cisplatin
PubMed: 37315583
DOI: 10.1016/j.radonc.2023.109742 -
Value in Health Regional Issues Sep 2023This study aimed to evaluate the cost-effectiveness of anti-epidermal growth factor receptor (cetuximab and panitumumab) or anti-vascular endothelial growth factor...
OBJECTIVES
This study aimed to evaluate the cost-effectiveness of anti-epidermal growth factor receptor (cetuximab and panitumumab) or anti-vascular endothelial growth factor (bevacizumab) monoclonal antibodies associated with conventional chemotherapy (CT) (fluorouracil and leucovorin with irinotecan) as a first-line treatment for unresectable metastatic colorectal cancer.
METHODS
A partitioned survival analysis model was adopted to simulate direct health costs and benefits comparing therapeutic options in a 10 years' time horizon. Model data were extracted from the literature and costs were obtained from Brazilian official government databases. The analysis considered the perspective of the Brazilian Public Health System; costs were measured in local currency (BRL) and benefits in quality-adjusted life-years (QALY). A 5% discount rate was applied to costs and benefits. Alternative willingness-to-pay scenarios, varying from 3 to 5 times the cost-effectiveness threshold established in Brazil, were estimated. The results were presented incremental cost-effectiveness ratio (ICER), and both deterministic and probabilistic sensitivity analyses were performed.
RESULTS
The most cost-effective choice would be the association of CT with panitumumab, with an ICER of $58 330.15/QALY compared with isolated CT. The second-best option was CT with bevacizumab and panitumumab, with an ICER of $71 195.40/QALY compared with panitumumab alone. Although having higher costs, the second-best option was the most effective. Both strategies were cost-effective in part of the Monte Carlo iterations, considering the 3× threshold.
CONCLUSIONS
The therapeutic option CT + panitumumab + bevacizumab represents the most significant effectiveness gain in our study. It is the second-lowest cost-effectiveness, and this option includes monoclonal antibodies association for patients with and without KRAS mutation.
Topics: Humans; Antibodies, Monoclonal; Panitumumab; Bevacizumab; Cost-Effectiveness Analysis; Colorectal Neoplasms; Cost-Benefit Analysis
PubMed: 37207532
DOI: 10.1016/j.vhri.2023.04.003 -
Digestive and Liver Disease : Official... Feb 2024In metastatic RAS wild-type colorectal cancer (CRC), induction combination chemotherapy doublets (CT) with an anti-EGFR agent are considered the primary treatment. We... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
In metastatic RAS wild-type colorectal cancer (CRC), induction combination chemotherapy doublets (CT) with an anti-EGFR agent are considered the primary treatment. We performed a network meta-analysis (NMA) to compare the relative efficacy of different maintenance treatments for advanced RAS wild-type CRC.
MATERIALS AND METHODS
PubMed, EMBASE and Cochrane, from database inception until December 2021 were used. Randomized clinical trials enrolling adults with advanced RAS wild-type CRC and providing overall survival (OS) and/or progression-free survival (PFS) data PRISMA guidelines for NMA were followed. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities.
RESULTS
A total of 7 randomized phase 2 trials were included (for a total of 1286 patients). Compared to depotentiation treatments, continuous CT + anti-EGFR was not significantly superior to other maintenance regimens for OS and was ranked as the best option for NMA (SUCRA p-score=0.69). Conversely, in the PFS analysis, single-agent fluoropyrimidines + anti-EGFR was ranked as the best treatment (SUCRA p-score=0.60).
CONCLUSIONS
Maintaining chemotherapy doublet + anti-EGFR until progression appears to be the best first-line strategy in terms of OS for advanced unresectable RAS wild-type mCRC treatment. However, fluoropyrimidines single-agent + cetuximab or panitumumab represent a reasonable choice regarding PFS.
Topics: Adult; Humans; Network Meta-Analysis; Panitumumab; Colorectal Neoplasms; Cetuximab; Colonic Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Randomized Controlled Trials as Topic
PubMed: 37369616
DOI: 10.1016/j.dld.2023.06.008 -
World Journal of Surgical Oncology Nov 2023The meta-analysis aimed to assess the clinical efficacy of chemotherapeutic triplet-drug regimen combined with anti-EGFR antibody in patients with initially unresectable... (Meta-Analysis)
Meta-Analysis
The meta-analysis aimed to assess the clinical efficacy of chemotherapeutic triplet-drug regimen combined with anti-EGFR antibody in patients with initially unresectable metastatic colorectal cancer (mCRC). A systematic literature search was performed in PubMed Publisher. Studies evaluating FOLFOXIRI combine with panitumumab or cetuximab as the therapy for initially unresectable mCRC were included. The primary outcome was objective response rate (ORR) and rate of R0 resections. The secondary outcomes included overall survival (OS), progression-free survival (PFS), and grades 3 or 4 adverse events. R software (version 4.0.2) and RevMan (version 5.3) were used to analyze the extracted data. The studies included were published between 2010 and 2021, involving four single-arm phase II trials and two randomized phase II trials. A total of 6 studies with 282 patients were included. The data showed a significant benefit for the FOLFOXIRI + anti-EGFR antibody arm compared with FOLFOXIRI arm (RR 1.33; 95% CI, 1.13-1.58; I = 0%, P < 0.05). The pooled ORR and pooled rate of R0 resection in patients who receiving FOLFOXIRI + anti-EGFR antibody were 85% (95% CI, 0.78-0.91; I = 58%) and 42% (95% CI, 0.32-0.53; I = 62%), respectively. The range of median PFS between all the six studies was 9.5-15.5 months, with weighted pooled median PFS mean 11.7 months. The range of median OS between all the four studies was 24.7-37 months, with weighted pooled median PFS mean 31.9 months. The common grades 3 and 4 adverse events were diarrhea and neutropenia. Our findings show that triplet-drug chemotherapy (FOLFOXIRI) combined with anti-EGFR antibody (panitumumab or cetuximab) represents a very effective therapeutic combination associated with a significant ORR and R0 rection rate for patients with molecularly unselected and surgically unresectable metastatic CRC.
Topics: Humans; Panitumumab; Cetuximab; Colorectal Neoplasms; Treatment Outcome; Colonic Neoplasms; Rectal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Leucovorin; Clinical Trials, Phase II as Topic; Randomized Controlled Trials as Topic
PubMed: 37978547
DOI: 10.1186/s12957-023-03256-7 -
Anti-cancer Drugs Jun 2024Colorectal cancer (CRC) ranks third in global cancer prevalence, with 40% presenting as metastatic colorectal cancer (mCRC). KRAS mutations in mCRC patients confer...
Colorectal cancer (CRC) ranks third in global cancer prevalence, with 40% presenting as metastatic colorectal cancer (mCRC). KRAS mutations in mCRC patients confer resistance to anti-EGFR treatments. Promising inhibitors such as sotorasib and adagrasib targeting KRASG12C mutations have demonstrated efficacy. Herein, we present a heavily pretreated mCRC case with a progression-free survival of 12 months with sotorasib and panitumumab. In 2017, a 27-year-old male presented with abdominal pain and received a diagnosis of stage IIIC KRAS G12C mutant CRC. Following surgery and adjuvant chemotherapy, he developed metastases in the liver and lungs in 2020. Treatment with FOLFIRINOX and bevacizumab, and later FOLFIRI and bevacizumab, with surgeries and local interventions resulted in partial responses. Upon disease progression, sotorasib and panitumumab were initiated, achieving a complete metabolic response. After 12 months of progression-free survival, oligoprogressive liver lesions were surgically resected. This case highlights the remarkable outcome of a heavily treated KRAS G12C mutant mCRC patient. The combination of sotorasib and panitumumab, along with multidisciplinary approaches including surgery and local interventions, played an important role in our patient's survival.
Topics: Male; Humans; Adult; Panitumumab; Bevacizumab; Antineoplastic Combined Chemotherapy Protocols; Proto-Oncogene Proteins p21(ras); Antibodies, Monoclonal; Progression-Free Survival; Camptothecin; Pancreatic Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms; Mutation; Piperazines; Pyridines; Pyrimidines
PubMed: 38451823
DOI: 10.1097/CAD.0000000000001587 -
Frontiers in Oncology 2024
PubMed: 38327740
DOI: 10.3389/fonc.2024.1366383 -
European Radiology Dec 2023Several barriers hamper recruitment of diverse patient populations in multicenter clinical trials which determine efficacy of new systemic cancer therapies. (Clinical Trial)
Clinical Trial
BACKGROUND
Several barriers hamper recruitment of diverse patient populations in multicenter clinical trials which determine efficacy of new systemic cancer therapies.
PURPOSE
We assessed if quantitative analysis of computed tomography (CT) scans of metastatic colorectal cancer (mCRC) patients using imaging features that predict overall survival (OS) can unravel the association between ethnicity and efficacy.
METHODS
We retrospectively analyzed CT images from 1584 mCRC patients in two phase III trials evaluating FOLFOX ± panitumumab (n = 331, 350) and FOLFIRI ± aflibercept (n = 437, 466) collected from August 2006 to March 2013. Primary and secondary endpoints compared RECIST1.1 response at month-2 and delta tumor volume at month-2, respectively. An ancillary study compared imaging phenotype using a peer-reviewed radiomics-signature combining 3 imaging features to predict OS landmarked from month-2. Analysis was stratified by ethnicity.
RESULTS
In total, 1584 patients were included (mean age, 60.25 ± 10.57 years; 969 men). Ethnicity was as follows: African (n = 50, 3.2%), Asian (n = 66, 4.2%), Caucasian (n = 1413, 89.2%), Latino (n = 27, 1.7%), Other (n = 28, 1.8%). Overall baseline tumor volume demonstrated Africans and Caucasians had more advanced disease (p < 0.001). Ethnicity was associated with treatment response. Response per RECIST1.1 at month-2 was distinct between ethnicities (p = 0.048) with higher response rate (55.6%) in Latinos. Overall delta tumor volume at month-2 demonstrated that Latino patients more likely experienced response to treatment (p = 0.021). Radiomics phenotype was also distinct in terms of tumor radiomics heterogeneity (p = 0.023).
CONCLUSION
This study highlights how clinical trials that inadequately represent minority groups may impact associated translational work. In appropriately powered studies, radiomics features may allow us to unravel associations between ethnicity and treatment efficacy, better elucidate mechanisms of resistance, and promote diversity in trials through predictive enrichment.
CLINICAL RELEVANCE STATEMENT
Radiomics could promote clinical trial diversity through predictive enrichment, hence benefit to historically underrepresented racial/ethnic groups that may respond variably to treatment due to socioeconomic factors and built environment, collectively referred to as social determinants of health.
KEY POINTS
•Findings indicate ethnicity was associated with treatment response across all 3 endpoints. First, response per RECIST1.1 at month-2 was distinct between ethnicities (p = 0.048) with higher response rate (55.6%) in Latinos. •Second, the overall delta tumor volume at month-2 demonstrated that Latino patients were more likely to experience response to treatment (p = 0.021). Radiomics phenotype was also distinct in terms of tumor radiomics heterogeneity (p = 0.023).
Topics: Aged; Humans; Male; Middle Aged; Colonic Neoplasms; Ethnicity; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 37368111
DOI: 10.1007/s00330-023-09862-z -
Supportive Care in Cancer : Official... Aug 2023Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies are effective in treating RAS wild-type metastatic colorectal cancer (mCRC). However, their...
PURPOSE
Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies are effective in treating RAS wild-type metastatic colorectal cancer (mCRC). However, their administration induces skin toxicity, markedly reducing patients' quality of life. This study is aimed at identifying the risk factors associated with anti-EGFR monoclonal antibody-induced skin toxicities.
METHODS
Patients with mCRC (n = 116) who received anti-EGFR monoclonal antibody treatment were retrospectively evaluated. Primary endpoint was evaluation of the risk factors for grade ≥ 2 overall skin toxicities during all the treatment periods. Furthermore, factors associated with each grade ≥ 2 skin symptoms were assessed.
RESULTS
Incidence of total grade ≥ 2 skin toxicity symptoms was 61.2%, and those of grade ≥ 2 rash, dry skin, fissures, and paronychia were 34.5%, 25.9%, 20.7%, and 25.0%, respectively. Multivariate logistic regression analyses revealed that liver metastasis was an independent risk factor for overall grade ≥ 2 skin toxicities (adjusted odds ratio [OR], 2.88; 95% confidence interval [CI], 1.22-6.78; P = 0.02) and prophylactic administration of antibiotics as a preventive factor (OR 0.10; 95%CI 0.01-0.91; P = 0.04). For grade ≥ 2 rash, prophylactic use of systemic antibiotics and topical steroid ointment was a preventive factor (OR 0.37; 95%CI 0.16-0.89; P = 0.03). Moreover, liver metastasis (OR 8.37; 95%CI 1.98-35.47; P = 0.004) and prophylactic administration of antibiotics (OR 0.15; 95%CI 0.03-0.76; P = 0.02) were significantly associated with grade ≥ 2 paronychia.
CONCLUSION
Liver metastasis was suggested to be a risk factor for the incidence of overall grade ≥ 2 skin toxicities; moreover, preemptive systemic antibiotic administration drastically decreased this risk during all periods of anti-EGFR treatment for mCRC.
Topics: Humans; Panitumumab; Cetuximab; Paronychia; Quality of Life; Retrospective Studies; Colorectal Neoplasms; ErbB Receptors; Antibodies, Monoclonal; Antineoplastic Agents; Exanthema; Colonic Neoplasms; Rectal Neoplasms; Anti-Bacterial Agents; Risk Factors
PubMed: 37528282
DOI: 10.1007/s00520-023-07973-3 -
Oncology Letters Sep 2023Drug-induced thrombocytopenia is an adverse reaction characterized by accelerated platelet destruction. The present study described a case of thrombocytopenia that...
Drug-induced thrombocytopenia is an adverse reaction characterized by accelerated platelet destruction. The present study described a case of thrombocytopenia that occurred during treatment with panitumumab. A female patient aged 49 years with metastatic rectal adenocarcinoma was treated with 9 out of 12 cycles of therapy with the standard of care, 5-fluorouacil (5-FU), oxaliplatin and folic acid, in association with panitumumab. During cycle 10, the patient developed severe thrombocytopenia, so the therapy was adjusted to a lower dosage; however, during cycle 11, after administration of panitumumab and before administration of 5-FU or oxaliplatin, the patient again presented with severe thrombocytopenia, with a platelet count <2×10/l. Immunology test results were negative apart from anti-nucleus antibodies (titration, 1:160). Naranjo's algorithm was used to establish the relationship between the use of panitumumab and thrombocytopenia onset and a score of 6 ('probable') was found. The temporal link between the onset of symptoms and administration of therapy, the relapse of thrombocytopenia after re-administration of the drug during cycle 11 (positive rechallenge) and Naranjo score of 6 ('probable') are crucial elements for establishing the causal relationship and the probability that thrombocytopenia was related to the administration of panitumumab. The patient then underwent two cycles of therapy with 5-FU, folic acid and irinotecan, in association with bevacizumab, experiencing again the same adverse event. Treatment with monoclonal antibodies was suspended altogether in favor of a switch to trifluridine/tipiracil. No other serious adverse events were reported.
PubMed: 37600345
DOI: 10.3892/ol.2023.13984 -
Oral Surgery, Oral Medicine, Oral... Aug 2023The aim of this study was to report a case series of patients with metastatic colorectal cancer (mCRC) undergoing panitumumab-containing regimens affected by oral... (Review)
Review
Clinical characterization of stomatitis cases with an epithelial growth factor receptor inhibitor in metastatic colorectal cancer patients: A study of 7 cases and literature review.
OBJECTIVE
The aim of this study was to report a case series of patients with metastatic colorectal cancer (mCRC) undergoing panitumumab-containing regimens affected by oral lesions and to review the current literature.
STUDY DESIGN
Electronic medical records of mCRC patients referred to treat mouth sores during the treatment with the anti-epithelial growth factor receptor (EGFR)-panitumumab-were retrospectively reviewed. Patients' characterization, clinical profile of oral lesions, and management outcomes were documented. Additionally, modifications or discontinuation of the antineoplastic treatment as well as the occurrence of other adverse events (AEs) were analyzed.
RESULTS
A total of 7 patients were included. The oral lesions appeared in a median time of 10 days (range 7-11 days) after the drug administration. The median reported pain score was 5 (range 1-9), causing feeding discomfort. Oral lesions with a marked aphthous-like appearance, among others, occurred in all cases and involved nonkeratinized mucosa more likely. At least 1 patient had dose reduction of the treatment and 1 patient needed discontinuation due to panitumumab-associated stomatitis. Dermatologic AEs were the most prevalent. Clinical improvement was obtained with topical corticosteroid therapy and/or photobiomodulation.
CONCLUSIONS
In summary, panitumumab-containing regimens were associated with a particular pattern of oral lesions consistent with stomatitis. This event may eventually affect the tolerability of the treatment in patients with mCRC.
Topics: Humans; Panitumumab; Antibodies, Monoclonal; Colorectal Neoplasms; Retrospective Studies; ErbB Receptors; Receptors, Growth Factor; Stomatitis; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37316420
DOI: 10.1016/j.oooo.2023.01.004