Evaluating the Efficacy and Safety of Kinesiology Tape Wrapping as Adjunct Therapy for Epidermal Growth Factor Receptor–Induced Paronychia

We compared the response rates, survival rates, and safety profile of epidermal growth factor receptor (EGFR) inhibitors with non-targeted chemotherapy and older EGFR inhibitors when used to treat advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. We searched PubMed, Cochrane Central Register of Controlled Trials, and clinicaltrial.- gov for randomized controlled trials published until 11-Feb-2020. Treatment outcomes were compared between EGFR inhibitor and pooled comparator; a subgroup analysis compared outcomes between EGFR inhibitor and non-targeted chemotherapy, and between newer and older EGFR inhibitors. Twenty-one studies with 4,250 unique patients were included. Significantly higher objective response rate (ORR) (odds ratio (OR) 2.28; 95% CI 2.00-2.61), higher disease control rate (DCR) (OR 2.3; 95% CI 1.88-3.06), and longer progression-free survival (PFS) (Hazard ratio (HR) 0.56; 95% CI 0.52-0.60) were observed in the EGFR inhibitor group compared to the pooled comparator group. Subgroup analysis revealed that the ORR, DCR, and PFS were significantly higher with EGFR inhibitors than non-targeted chemotherapy, and only PFS (and not ORR and DCR) was significantly longer with newer EGFR inhibitors than the older EGFR inhibitors. Overall survival (OS) was not significantly different between EGFR inhibitors and pooled comparator (HR 0.91; 95% CI 0.83-1.00) as well as in either of the subgroup analyses. Adverse events ≥ grade 3 and treatment discontinuation were significantly higher with non-targeted chemotherapy compared to the EGFR inhibitors. The benefits of prolongation of ORR, DCR, and PFS might not imply significantly improved OS after therapy with EGFR inhibitors when compared with non-targeted chemotherapy or older EGFR inhibitors.

Paronychia is a common adverse event caused by epidermal growth factor receptor (EGFR) inhibitors. However, high rates of post-treatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion for EGFR inhibitor-induced paronychia. Furthermore, poor wound healing and malnutrition were common conditions found in cancer patients. The aim of this study is to find an effective, pain-relieving, and noninvasive treatment for patients with severe paronychia induced by EGFR inhibitors. Data from a series of 35 non-small cell lung cancer cases suffering from EGFR inhibitor-induced paronychia with pyogenic granuloma-like lesions of digits treated with betaxolol 0.25% ophthalmic solution once daily were collected and analyzed. Of the 35 patients suffering from grade 2 or 3 paronychia with pyogenic granuloma-like lesions induced by EGFR inhibitors, 34 (97.1%) demonstrated complete resolution and only one (2.9%) had partial resolution after 12weeks of topical betaxolol treatment. The grading of paronychia according to the Common Terminology Criteria for Adverse Events decreased from an average of 2.29 to 0.63 after 4weeks of treatment (P=5.55×10-16 ). All the patients had significant improvement (50% pain reduction), as their pain visual analogue scale scores decreased from an average of 7.06 to 2.26 after one week of treatment (P=6.11×10-25 ). Betaxolol 0.25% ophthalmic solution is an effective, safe, and pain-relieving treatment for patients suffering from EGFR inhibitor-induced paronychia with pyogenic granuloma-like lesions and deep fissures.

The Challenges of Third-Generation EGFR Tyrosine Kinase Inhibitors in the Therapy of Advanced NSCLC

Pregabalin (PGB) and duloxetine (DLX) are commonly used first-line medications in the clinical management of painful diabetic neuropathy (PDN), yet high-quality comparative evidence is limited. This meta-analysis evaluates the comparative efficacy and safety of PGB versus DLX, focusing on efficacy outcomes such as pain reduction and mental health, and safety outcomes including adverse events in PDN patients. We searched electronic databases for relevant studies assessing the efficacy and safety of PGB and DLX in PDN. The primary outcomes were the mean change of the visual analog scale (VAS) and the improvement ratio for patients achieving ≥ 50% pain reduction. Secondary outcomes, including the numeric rating scale (NRS) for pain, the short form 12 health survey (SF-12), and related adverse events. A random-effects meta-analysis was performed to evaluate these outcomes. We analyzed 19 studies involving 4,483 patients. PGB significantly reduced VAS scores at 24 weeks (MD = -0.38; 95% CI [-0.45, -0.31], P < 0.0001) and decreased the mental component of SF-12 compared to DLX (MD = -3.36; 95% CI [-6.64, -0.07], P = 0.05) and lower rates of achieving >50% pain reduction (RR = 0.88; 95% CI [0.79, 0.98], P = 0.03). Regarding safety, PGB showed a lower incidence of several adverse events, including anorexia, decreased appetite, diarrhea, nausea, and vomiting. However, no significant differences in VAS scores were observed between PGB and DLX at 1 week, 2 weeks, 4 weeks, 6 weeks, 8 weeks, and 12 weeks, with similar results observed in NRS. We found that PGB and DLX showed similar efficacy in relieving PDN. Ultimately, the two drugs' similar effectiveness and different safety profiles highlight the importance of considering patient-specific factors when choosing the appropriate treatment.

e19155 Background: Epidermal growth factor receptor (EGFR) inhibitors are suspected of being a potential cause of interstitial lung disease (ILD). This speculation is based largely on case reports and series in which it is difficult to establish causality. In this meta-analysis we evaluated randomized controlled trials (RCTs) involving EGFR inhibitors to verify if a relationship exists between exposure to EGFR inhibitors and development of ILD and other pulmonary-related events. Methods: EMBASE and Medline were searched for all RCTs evaluating cetuximab, gefitinib or erlotinib in non-small cell lung cancer (NSCLC). Studies were disqualified if the control contained any EGFR inhibitor or drug known to cause ILD. Thirty-one RCTs with 15,736 patients were identified. The primary outcome was ILD incidence. ILD is poorly defined and there is overlap with other pulmonary related outcomes including pneumonia, acute respiratory failure (ARF) and pneumonitis, and these were therefore secondary outcomes of interest. For all outcomes, a fixed-effects meta-analysis was performed. Results: For the primary outcome, there is a 173% increased risk of ILD among patients given EGFR inhibitors (RR 2.73, 95% CI: 1.74-4.23, p&lt;0.001) across 15 RCTs that report on ILD incidence. Among secondary endpoints, there is an 86% increased risk of pneumonia (RR 1.86, 95% CI 1.36-2.53, p&lt;0.001), a 19% increased risk of pneumonitis (RR 1.19, 95% CI: 0.62-2.27, p=0.59) and a 33% increased risk of ARF (RR 1.33, 95% CI: 0.65-2.72, p=0.44) among patients given EGFR inhibitors. There is minimal heterogeneity across trials for all above outcomes. Conclusions: EGFR inhibitors play a direct role in causing or contributing to ILD progression in patients with NSCLC who are susceptible to alveolar damage from prior chemoradiation therapy. Additionally, EGFR inhibitors seem to be associated with an increased risk for other pulmonary related events.This research suggests that caution should be undertaken in administering EGFR inhibitors to patients with poor baseline lung function or pre-existing pulmonary disease.

BackgroundIt has recently been shown that patients treated with epidermal growth factor receptor (EGFR) inhibitors often develop various cutaneous adverse events. While the pathogenesis underlying these events remains unclear, the relationship between skin toxicity induced by EGFR inhibitors and the sebaceous glands that express EGFR has been previously reported.ObjectivesThe primary aim of this study was to determine the relationship between cutaneous sebum levels and acneiform rash, a typical skin toxicity of EGFR inhibitors, by measuring the sebum levels before and after EGFR inhibitor treatment.MethodsEight patients diagnosed with non–small cell lung cancer (NSCLC) (three men and five women with an average age of 69.3 years) who were initiated on treatment with EGFR inhibitors (either gefitinib [Iressa®] or erlotinib [Tarceva®]) were enrolled. Using a Sebumeter®, sebum levels in the face, chest, and back of each patient were measured before and after EGFR inhibitor treatment. The development of acneiform rash in each skin region was also assessed.ResultsChanges in sebum level along with the development of an acneiform rash were observed after patients were started on EGFR inhibitor treatment. Patients who developed an EGFR inhibitor–induced acneiform rash tended to have higher pretreatment sebum levels (baseline) than did patients who did not experience an acneiform rash. At each time point measurement, sebum levels were found to be significantly higher in patients who had developed an acneiform rash at that time. Patients who developed rash during treatment showed greater differences in sebum level compared with pretreatment baseline.ConclusionPatients who had increased levels of sebum or whose sebum levels showed greater change from pretreatment baseline developed an acneiform rash, suggesting that sebaceous gland activity may be involved in the mechanism underlying the development of acneiform rash, in patients treated with EGFR inhibitors.

ES17.03 Imaging of Pneumonitis

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase ubiquitously expressed in different tissues, including the heart. EGFR is dysregulated in several kinds of cancer, as well as in heart diseases. Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease and one of the underlying mechanisms is impaired desmosome turnover. The intercalated disc (ICD) not only provides cellular cohesion but can also provide the structural framework of a signaling hub. Thus, stabilizing desmosome integrity, thereby enhancing cardiomyocyte stability, may provide potential new treatment options. In this study, we investigated the role of EGFR inhibition on cardiomyocyte cohesion under physiological as well as under pathophysiological conditions using the cardiomyocyte‐specific plakoglobin knockout (Jup‐/‐) ACM model in which EGFR was upregulated. Dissociation assays in HL‐1 cells and murine cardiac slice cultures showed that EGFR inhibition by erlotinib similar to SRC inhibition enhanced cardiomyocyte cohesion. Immunoprecipitation showed an interaction of EGFR, desmoglein 2 (DSG2) and desmoplakin (DP), indicating that altered EGFR signaling might affect desmosomes. Immunostainings and atomic force microscopy (AFM) revealed enhanced DSG2 localization and binding at the cell borders upon EGFR inhibition. In addition, during desmosome assembly induced by a Ca2+‐switch, DSG2 and DP were augmented at the cell borders after EGFR or SRC inhibition. Our study shows that EGFR inhibition by erlotinib leads to increased DSG2 binding and desmosome assembly, which stabilizes cardiomyocyte cohesion in the ACM mouse model. Because EGFR inhibition by erlotinib is already used in cancer patients, these data reveal a potential new therapeutic strategy in ACM.

The present study was designed to evaluate the efficacy and safety of a combination of helical tomotherapy (HT) or intensity-modulated radiotherapy (IMRT) and EGFR (epidermal growth factor receptor) inhibitor (Cetuximab or Nimotuzumab) with or without chemotherapy in patients with locally advanced hypopharyngeal carcinoma. The retrospective study included forty-six patients (12 stage III and 34 stage IV) with locally advanced hypopharyngeal cancer. Among them, 20 were treated with induction chemotherapy with docetaxel and cisplatin (TP) followed by concurrent chemoradiotherapy with cisplatin and EGFR inhibitor, 13 received concurrent chemoradiotherapy with cisplatin and EGFR inhibitor, and 13 were treated with concurrent radiotherapy plus EGFR inhibitor. HT and IMRT were performed in 33 and 13 patients, respectively. Side effects were evaluated with the established CTCAE (Common Terminology Criteria for Adverse Events) 3.0 criteria. The median follow-up time was 39.4 months (range 3-69 months). All patients completed the planned RT without any treatment breaks. The 3-year local control survival, disease-free survival, overall survival, and laryngeal preservation survival rates were 66.8%, 59.0%, 68.9%, and 86.7%, respectively. The most common grade 3 or higher side effect was oropharyngeal mucositis. One patient required dilatation of a pharyngeal stricture 18 months after treatment. No patient required percutaneous gastrostomy and tracheostomy tube. The treatment with EGFR inhibitor in combination with non-surgical combined modality in patients with hypopharyngeal carcinoma was well tolerated and resulted in encouraging laryngeal preservation survival rate. HT or IMRT, EGFR inhibitor, and effective management of severe oropharyngeal mucositis contributed to the positive outcomes.

Axl Receptor Axis: A New Therapeutic Target in Lung Cancer

Epidermal growth factor receptor – inhibition (EGFR-I) in the treatment of neuropathic pain

Epidermal growth factor receptor (EGFR) inhibitors for metastatic colorectal cancer.

BackgroundThe efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non‐small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor‐related skin adverse events (ERSEs).Materials and MethodsThis placebo‐controlled, double‐blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily.ResultsEfficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex‐16 after treatment were significantly different among arms (mean ± SD: −5.2 ± 8.6 for arm 1, −11.7 ± 14.2 for arm 2, and − 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm.ConclusionEGF ointment is effective for managing ERSEs. It can also improve patients’ QoL compared with placebo. Clinical trial identification number. NCT02284139Implications for PracticePatients with non‐small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor‐related skin adverse events.

To evaluate the therapeutic effects, larynx preservation and adverse events of non-surgical combined treatments for laryngeal organ preservation in locally advanced laryngeal squamous cell carcinomas(SCCs). Forty-six patients with locally advanced laryngeal carcinoma (T2-4, N0-N3) were treated individually with non-surgical combined treatments for larynx preservation (LP). These treatments included concurrent chemoradiotherapy (CCRT)(±epidermal growth factor receptor (EGFR) inhibitor), induction chemotherapy (ICT) followed by CCRT(± EGFR inhibitor), or concurrent radiotherapy and EGFR inhibitor. Radiation therapy was given to a total dose of 60-70 Gy. The Kaplan-Meier method was used to determine the overall survival. Side-effects were evaluated with the established Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria. The average follow-up time was 31.8 months (range 6-95 months). All patients completed the planned radiotherapy without treatment breaks, and 45(97.8%) of 46 patients completed the planned chemotherapy.The 3-year and 5-year overall survival rates were 87.3%and 67.2%, respectively.The 5-year larynx preservation rate was 100.0%. The 3-year and 5-year progression free survival rates were 95.1% and 87.7%, respectively. The most common acute side effect in grade 3 was oropharyngeal mucositis. After treatment, tracheotomy was still required in 2 patients with glottis cancer for laryngeal edema or stenosis. No patient depended on a percutaneous gastrostomy and experienced speech impairment. Patients with locally advanced laryngeal cancer can be offered non-surgical combined treatments for laryngeal preservation and the high quality of life, showing a higher laryngeal preservation survival rate with minimal toxicities.

Ovarian cancer is the seventh most common cause of cancer death in women world-wide. Treatment consists of a combination of surgical debulking and platinum-based chemotherapy, alone or in combination with paclitaxel. Between 55% and 75% of women who respond to first-line therapy relapse within twoyears of completing treatment. Second-line chemotherapy is palliative and aims to reduce symptoms and prolong survival. Increased understanding about the molecular basis of ovarian cancer has led to the development of novel agents, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, and their effectiveness and toxicities in women with advanced ovarian cancer needs to be assessed. To compare the effectiveness and toxicities of epidermal growth factor receptor (EGFR) inhibitors alone or in combination with standard chemotherapy in the treatment of ovarian cancer. We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) Issue 4, 2010, MEDLINE and EMBASE up to October 2010. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies, and contacted experts in the field. Randomised controlled trials (RCTs) comparing anti-EGFR agents with or without conventional chemotherapy versus conventional chemotherapy alone or no treatment in women with histologically proven ovarian cancer. Two review authors independently abstracted data and assessed risk of bias. We reported adjusted hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received gemcitabine plus pertuzumab and gemcitabine plus placebo. We found only one completed and three ongoing RCTs that met our inclusion criteria. The completed trial randomised 131 women with relapsed ovarian cancer to receive gemcitabine and pertuzumab or placebo and gemcitabine (control). There was no statistically significant difference in overall survival (OS), progression-free survival (PFS) and response between women who received gemcitabine and pertuzumab and those who received control, although PFS approached borderline significance (adjusted HR = 0.66, 95% CI 0.43 to 1.03; P = 0.06). The trial reported a higher rate of adverse events in the gemcitabine and pertuzumab arm for most outcomes, but most were not statistically significant (although many approached borderline significance) because the trial lacked statistical power due to its relatively small size and the low number of observed events. The trial was at moderate risk of bias. EGFR inhibitors, including pertuzumab, may add activity to conventional chemotherapy for treatment of platinum-resistant ovarian cancer. Certain subsets of women with particularly aggressive tumours resistant to conventional chemotherapy may benefit from EGFR inhibitor treatment. Further RCTs are necessary before EGFR inhibitors are introduced as first- or second-line treatment of ovarian cancer.