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Oncology Letters Aug 2023The current treatment options for epidermal growth factor receptor (EGFR) mutation-positive lung cancer in the elderly with tyrosine kinase inhibitor (TKI) resistance...
The current treatment options for epidermal growth factor receptor (EGFR) mutation-positive lung cancer in the elderly with tyrosine kinase inhibitor (TKI) resistance are limited. Although chemotherapy combined with vascular endothelial growth factor inhibitors significantly improves progression-free survival (PFS) in TKI-resistant patients, it often cannot be tolerated in elderly patients, leading to treatment failure. Anlotinib is a small molecule inhibitor made in China. The application of low-dose anlotinib in elderly patients with TKI-resistant lung cancer deserves further investigation. A total of 48 elderly patients with non-small cell lung cancer (NSCLC) were enrolled to evaluate the efficacy of anlotinib combined with continuous EGFR-TKI vs. anlotinib monotherapy in patients with acquired EGFR-TKI resistance. Anlotinib was administered at a dose of 6-8 mg per day, lower than the normal dose and known as a low dose, which is well tolerated in elderly patients. There were 25 cases in the combination group and 23 cases in the anlotinib monotherapy group. The primary endpoint of the present study was PFS, and the secondary endpoints were overall survival (OS), response rate and toxicity. The median PFS (mPFS) was significantly longer in the combination group than that in the anlotinib monotherapy group: 6.0 months [95% confidence interval (CI), 4.35-7.65] compared with 4.0 months (95% CI, 3.38-4.62) (P=0.002). Analysis of the subgroups showed similar trends in results. The median OS was 32 months (95% CI, 22.04-41.96) in the combination group and 28 months (95% CI, 27.13-28.87) in the anlotinib monotherapy group (P=0.217). According to stratification analysis, second-line treatment with anlotinib combined with EGFR-TKI resulted in a better mPFS than third-line treatment (7.5 vs. 3.7 months, HR=3.477; 95% CI, 1.117-10.820; P=0.031). In the combination group, patients with gradual/local progression after EGFR-TKI failure had a longer mPFS than those with dramatic progression (7.5 vs. 6.0 months, HR=5.875; 95% CI, 1.414-10.460; P=0.015). Multivariate analyses showed that continuous EGFR-TKI combined with anlotinib after EGFR-TKI resistance was associated with longer PFS (P=0.019), whereas dramatic progression (P=0.014) had a detrimental effect on follow-up treatment. Grade 2 adverse events (AEs) were reported in four patients (17.39%) in the anlotinib monotherapy group and eight patients (32.00%) in the combination group. Of these, the most common grade 2 AEs were hypertension, fatigue, diarrhea, paronychia, mucositis and transaminase elevation. There were no grade 3/4/5 AEs. In conclusion, the present study demonstrated that low-dose anlotinib combined with EGFR-TKI is superior to anlotinib alone following EGFR-TKI failure, making it the preferred regimen for elderly patients with acquired EGFR-TKI resistance.
PubMed: 37415629
DOI: 10.3892/ol.2023.13909 -
Targeted Oncology Jun 2024Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) remain the frontline standard of care for patients with EGFR-mutant non-small cell lung cancer....
BACKGROUND
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) remain the frontline standard of care for patients with EGFR-mutant non-small cell lung cancer. An updated toxicity profile of EGFR-TKIs proves valuable in guiding clinical decision making.
OBJECTIVE
This study comprehensively assessed the risk of EGFR-TKI-related adverse events (AEs) involving different systems/organs.
METHODS
We systematically searched PubMed, Embase, Web of Science, and Cochrane library for phase III randomized controlled trials comparing EGFR-TKI monotherapy with placebo or chemotherapy in patients with non-small cell lung cancer. The odds ratio (OR) of all-grade and high-grade adverse events (AEs) including dermatologic, gastrointestinal, hematologic, hepatic, and respiratory events was pooled for a meta-analysis. Subgroup analyses based on the control arm (placebo or chemotherapy) and individual EGFR-TKIs (erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib) were conducted.
RESULTS
Thirty-four randomized controlled trials comprising 15,887 patients were included. The pooled OR showed EGFR-TKIs were associated with a significantly increased risk of all-grade dermatologic AEs including paronychia, pruritus, rash, skin exfoliation, and skin fissures, gastrointestinal AEs including abdominal pain, diarrhea, dyspepsia, mouth ulceration, and stomatitis, hepatic AEs including elevated alanine aminotransferase and aspartate aminotransferase, and respiratory AEs including epistaxis, interstitial lung disease and rhinorrhea. Furthermore, a significantly increased risk of high-grade rash (OR 7.83, 95% confidence interval [CI] 5.11, 12.00), diarrhea (OR 2.10, 95% CI 1.44, 3.05), elevated alanine aminotransferase (OR 3.93, 95% CI 1.71, 9.03), elevated aspartate aminotransferase (OR 3.22, 95% CI 1.05, 9.92) and interstitial lung disease (OR 2.35, 95% CI 1.38, 4.01) was observed in patients receiving EGFR-TKIs. When stratified by individual EGFR-TKIs, gefitinib showed a significant association with all-grade and high-grade hepatotoxicity and interstitial lung disease.
CONCLUSIONS
Epidermal growth factor receptor tyrosine kinase inhibitors were associated with a significantly increased risk of various types of AEs. Clinicians should be vigilant about the risks of these EGFR-TKI-related AEs, particularly for severe hepatotoxicity and interstitial lung disease, to facilitate early detection and proper management.
PubMed: 38824269
DOI: 10.1007/s11523-024-01073-w -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... May 2024To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma.
OBJECTIVE
To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma.
METHODS
We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January, 2013 to December, 2021. The 5-year disease-free survival (DFS) and overall survival (OS) rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs group, =111), chemotherapy (CT group, =108) and clinical observation (CO group, =434).
RESULTS
In TKIs, CT, and CO groups, the 5-year DFS rates were 92.8%, 80.7%, and 81.7%, respectively, significantly higher in TKIs group than in CO group ( < 0.01). The 3-year OS rates of the 3 groups were 96.8%, 97.1%, and 91.7%, respectively. Subgroup analysis showed that in TKIs, CT, and CO groups, the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%, 84.0%, and 81.4%, respectively, significantly higher in TKIs group than in CO group ( < 0.05); the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%, 71.4%, and 83.5%, respectively. Multivariate COX regression analysis showed that age ( < 0.05; =0.631, 95% : 0.401-0.993), solid nodules ( < 0.01; =7.620, 95% : 3.037-19.121), micropapillary or solid component ( < 0.05; = 1.776, 95% : 1.010-3.122), lymphovascular invasion ( < 0.05; =2.981, 95% : 1.198-7.419), and adjuvant therapy ( < 0.01) were independent predictors of DFS. The most common adverse effects included rashes, paronychia, and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy, and TKIs were associated with a higher incidence of grade 3 or above adverse effects (44.4% 9.0%).
CONCLUSION
Adjuvant therapy with TKIs helps improve DFS in patients with stage IB (T3-4cmN0M0) lung adenocarcinoma but not in patients with T2ViscPlN0M0. Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.
Topics: Humans; Lung Neoplasms; Adenocarcinoma of Lung; Female; Male; Chemotherapy, Adjuvant; Neoplasm Staging; Middle Aged; Protein Kinase Inhibitors; Disease-Free Survival; Survival Rate; Postoperative Period; ErbB Receptors; Aged
PubMed: 38862458
DOI: 10.12122/j.issn.1673-4254.2024.05.22 -
BMC Cancer Oct 2023About 10% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are harbored as uncommon mutations. This study aimed to...
BACKGROUND
About 10% of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are harbored as uncommon mutations. This study aimed to explore the efficacy and safety of dacomitinib, a second-generation EGFR tyrosine kinase inhibitor (EGFR-TKIs), in treating uncommon EGFR-mutated advanced NSCLC.
METHODS
Treatment-naïve advanced NSCLC patients treated with dacomitinib at Hunan Cancer Hospital with uncommon EGFR mutations were evaluated. The primary endpoint was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety.
RESULT
Between December 2019 and December 2021, a total of 16 patients was included. Median PFS was 14.0 (95% CI 4.32-23.7) months, and median OS was not reached. ORR was 68.8% (95% CI 41.3 to 89.0%) and DCR was 93.8% (95%CI 69.8 to 99.8%), including three achieving complete remission (CR) and eight achieving partial remission (PR). Median PFS for patients with brain metastasis was 9.0 (95%CI 6.9 to 11.1) months. Intracranial ORR was 100%, including 2 CR and 4 PR. Major treatment-related adverse events (TRAEs) included rash (87.5%), paronychia (62.5%), oral ulcers (50.0%), and diarrhea (50.0%), none of which were ≥ grade 3 TRAEs.
CONCLUSIONS
Dacomitinib showed good activity and manageable toxicity in NSCLC patients with uncommon EGFR mutations.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Cohort Studies; Antineoplastic Agents; Protein Kinase Inhibitors; ErbB Receptors; Mutation
PubMed: 37840124
DOI: 10.1186/s12885-023-11465-2 -
JAAD Case Reports Mar 2024
PubMed: 38439765
DOI: 10.1016/j.jdcr.2024.01.014 -
Journal of the American Academy of... Nov 2023
Does the combination of cryotherapy and topical timolol solution superior to cryotherapy alone in the treatment of epidermal growth factor receptor inhibitor-induced paronychia? A double-blinded, left-to-right comparison, randomized controlled trial.
PubMed: 37422018
DOI: 10.1016/j.jaad.2023.06.040 -
BMC Cancer Feb 2024This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam.
BACKGROUND
This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam.
METHODS
This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability.
RESULTS
A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%).
CONCLUSIONS
Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.
Topics: Humans; Afatinib; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Cohort Studies; ErbB Receptors; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Retrospective Studies; Vietnam
PubMed: 38317094
DOI: 10.1186/s12885-024-11891-w -
Journal of Oncology Pharmacy Practice :... Mar 2024Despite the common occurrence of cetuximab (Cmab)-induced skin toxicity, management strategies are not well established. The traditional mainstay method consists of...
Efficacy and safety of adapalene gel as a reactive treatment for cetuximab-induced skin toxicity in recurrent or metastatic squamous cell carcinoma of the head and neck: A historical cohort comparison study.
INTRODUCTION
Despite the common occurrence of cetuximab (Cmab)-induced skin toxicity, management strategies are not well established. The traditional mainstay method consists of topical steroids, which, if used excessively, may give rise to other concerns. Alternatively, adapalene can activate epidermal growth factor receptor pathways to potentially alleviate these toxicities.
METHODS
We prospectively studied 31 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) who were eligible to use adapalene gel as a reactive treatment for topical steroid-refractory skin toxicity. For comparison, we retrospectively reviewed 99 patients with R/M SCCHN (historical control cohort) whose skin toxicity was mainly treated with topical steroids. We compared the frequency and severity of Cmab-induced skin toxicity, Cmab therapy status (e.g., dose modification), side effects caused by topical steroids and adapalene gel itself, and other medical interventions.
RESULTS
Adapalene gel was used by eight patients (25.8%) in the prospective cohort. Patients in the historical control cohort more frequently required escalation of topical steroid potency (34.3% vs. 12.9%, = 0.022). Although there was no statistically significant difference in the frequency of grade ≥3 facial skin rash and paronychia between the two cohorts, the prospective cohort showed a significantly shorter time to complete recovery from grade 2/3 paronychia (16 vs. 47 days, = 0.017). Further, while no skin infections were observed in the prospective cohort, 13 patients in the historical control cohort developed skin infections, especially periungual infection (0% vs. 13.1%, = 0.024). In addition, no patients in the prospective cohort received a dose reduction of Cmab due to skin toxicities, compared to 20 patients in the historical control cohort (0% vs. 20.2%, = 0.003). No apparent adapalene gel-related side effects were observed.
CONCLUSIONS
Adapalene gel may be an effective management option for topical steroid-refractory Cmab-induced skin toxicities and could improve compliance with Cmab therapy.
Topics: Humans; Cetuximab; Adapalene; Squamous Cell Carcinoma of Head and Neck; Prospective Studies; Retrospective Studies; Paronychia; Neoplasm Recurrence, Local; Skin Diseases; Head and Neck Neoplasms; Steroids; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37098185
DOI: 10.1177/10781552231171699 -
Journal of the American Academy of... Apr 2024
Topics: Humans; Dental Devices, Home Care; Nails; Nails, Ingrown; Toes
PubMed: 37062460
DOI: 10.1016/j.jaad.2023.04.012 -
Contact Dermatitis Apr 2024
Topics: Humans; Dermatitis, Allergic Contact; Epoxy Resins; Paresthesia; Dermatitis, Occupational; Nail Diseases; Patch Tests
PubMed: 38254251
DOI: 10.1111/cod.14506