Management of cutaneous toxicities under amivantamab (anti MET and anti EGFR bispecific antibody) in patients with metastatic non-small cell lung cancer harboring EGFR Exon20ins: towards a proactive, multidisciplinary approach.

CONTEXTE: The Epidermal Growth Factor Receptor (EGFR) is mutated in 10-15% of patients with lung adenocarcinoma. At metastatic stage EGFR tyrosine kinase inhibitors (TKIs) are used front line for patients harboring targetable mutations. Novel anti-EGFR therapies are being developed. Amivantamab is a bispecific anti-EGFR and anti-MET antibody with expected skin toxicities. OBJECTIVE: We developed here guidelines for prevention and treatment of cutaneous toxicities under amivantamab according to our experience at Institut Curie. MATERIEL & METHOD: The first patients with metastatic lung cancer harboring EGFR Exon20ins mutation, included in the phase 1 CHRYSALIS trial and cured at Institute Curie from November 1st 2019 until December 31st 2021 were selected for this work. Retrospectively, all cutaneous adverse events were registered and classified according to the CTCAE 6.0 classification, and actions we implemented to minimize and treat these adverse events were collected. We then developed guidelines based on these datas. RESULTS: A total of seven patients started amivantamab as monotherapy. The two most frequent dermatological adverse events were: acneiform rash and paronychia (100 % of patients). Other adverse events presented by the patients were reported: modification of hair growth with hypertrichosis in 50 % of men (n = 1/2) and hirsutism in 80 % of women (n = 4/5); skin abrasion of the scalp in 71 % (n = 5/7); and skin fissure in 57 % (n = 4/7). We recommend first a rigorous inspection of the skin and teguments to determine the risk rate to have dryer skin under treatment; second a prevention of paronychia/acneiform rash/and skin fissures with prophylactic tetracycline, skin moisturizing, and hygienic measures starting at least 14 days before treatment initiation; third a particular attention to the psychological impact of skin toxicities with access to psychological support. CONCLUSION: We propose here guidelines for the management of dermatological toxicities under amivantamab with a multidisciplinary approach for the proactive management of cutaneous toxicities with a focus on preventive actions.

Using betaxolol for the prevention of paronychia induced by epidermal growth factor receptor inhibitors: a case-control cohort study.

BACKGROUND: High rates of posttreatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion resulting from epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)-induced paronychia, which may even interrupt the course of treatment for EGFR-TKI therapy. Thus, we conducted this study to determine how effectively a topical ß-blocker, betaxolol, prevents EGFR-TKI-induced paronychia. METHODS: This case-control cohort study included a total of 131 non-small-cell lung cancer patients. The prevention group comprised 40 patients treated with topical betaxolol 0.25% solution to prevent paronychia while they received EGFR-TKI therapy. The control group comprised 91 patients who did not preventively use topical betaxolol 0.25% solution while receiving EGFR-TKI therapy. The patients' age, gender, antineoplastic regimen, duration of antineoplastic treatment before the appearance of lesions, number of involved digits (fingernails or toenails) with lesions, grading of paronychia, and pain score were recorded. RESULTS: In terms of the cumulative incidence of paronychia, significant differences (P < 0.01) were noted at both the 2nd and 3rd months after starting EGFR-TKIs. Furthermore, the average visual analogue scale scores were 3.125 and 6.29 in the prevention group and control group, respectively (P < 0.01). The average grades of paronychia were 1.5 and 2.12 in the prevention group and control group, respectively (P < 0.01). The average numbers of involved digits were 2.25 (range: 1-5 digits) in the prevention group and 3.03 (range: 1-7) in the control group (P = 0.07). CONCLUSIONS: Preventively using topical betaxolol can significantly decrease the incidence, VAS score, and grading of EGFR-TKI-induced paronychia.

Prophylactic management for taxane-induced nail toxicity: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was performed to assess the efficacy of cryotherapy and nail solution (NS) use in preventing nail toxicity (NT) induced by taxane-based chemotherapy. METHODS: PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov registry databases were searched for relevant studies published up to December 2018. The primary outcome was taxane-induced NT. Secondary outcomes were skin toxicity (ST), time to toxicity and patient comfort. RESULTS: We reviewed three randomised control trials and six prospective studies with 708 patients. For meta-analysis, taxane-induced NT grading was compared. NT and ST were significantly lower in the cryotherapy patients than in the controls (grade 1 NT: risk ratio [RR] = 0.51, 95% confidence interval [CI] = 0.30-0.89; grade 2-3 NT: RR = 0.36, 95% CI = 0.11-1.12; total NT: RR = 0.49; 95% CI = 0.30-0.79; ST: RR = 0.46, 95% CI = 0.33-0.64). The NS-treated patients exhibited significantly lower NT than the controls. CONCLUSIONS: Nail solution-treated or cryotherapy patients exhibited lower NT incidence and severity associated with taxane-based chemotherapy than the controls. For patients who can afford and comply with NS use or cryotherapy, these measures represent effective prophylactic management for taxane-induced NT and improve their quality of life and functional statuses. Further studies are needed to establish the routine usage protocols, long-term efficacy and safety for these interventions.

Skin problems and EGFR-tyrosine kinase inhibitor.

Epidermal growth factor receptor inhibition is a good target for the treatment of lung, colon, pancreatic and head and neck cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor was first approved for the treatment of advanced lung cancer in 2002. Epidermal growth factor receptor-tyrosine kinase inhibitor plays an essential role in the treatment of cancer, especially for patients harbouring epidermal growth factor receptor activating mutation. Hence, skin toxicity is the most concerning issue for the epidermal growth factor receptor-tyrosine kinase inhibitor treatment. Skin toxicity is bothersome and sometimes affects the quality of life and treatment compliance. Thus, it is important for physicians to understand the background and how to manage epidermal growth factor receptor-tyrosine kinase inhibitor-associated skin toxicity. Here, the author reviewed the mechanism and upfront preventive and reactive treatments for epidermal growth factor receptor inhibitor-associated skin toxicities.

Treatment and prevention of paronychia using a new combination of topicals: report of 30 cases.

AIM: Moderate and chronic paronychia is a common disease affecting the hand. Treatment can be effective but the affection is often recurrent, especially as an occupational disease. Moreover, this condition may be complicated by a Candida spp or by bacterial infections. Therefore, general preventive measures can be useful in maintaining health. The aim of this study was to investigate the efficacy and tolerability of a new combination of topical medications in the treatment and prevention of moderate and chronic paronychia. This formulation includes an insulating polymer (Syn-cell barrier), two topical antifungals (octopirox and climbazole) and a molecule with anti-inflammatory activity (corticoid-like repair). METHODS: Thirty adult subjects (age, 16-78 years; 24 females and 6 males) affected by moderate or chronic paronychia, with or without nail alterations, were evaluated. Included in the study were patients with allergic contact dermatitis (8), irritant contact dermatitis (19), psoriatic paronychia (2 patients), lichen planus of the nails (1 patient). Sometimes Candida spp or bacteria overlapped with paronychia (16 patients positive for Candida spp and 4 patients with bacterial paronychia), sometimes infectious paronychia was not associated with dermatitis of the hands. All 30 subjects were treated with a new cream formulation, three applications per day for 2 months. In 8 patients with proven and severe candidiasis of the nails, oral fluconazole 100 mg was added for 20 days. All patients with bacterial perionyxis took clarithromycin 500 mg twice daily for six days. Patients were then followed for 8 weeks. RESULTS: After two months of treatment, 26 patients responded to therapy. In particular, the treatment evaluation at the end of the follow-up period showed a clinical cure in 46.6% (14 patients), improvement in 40% (12 patients), and failure in 13.4% (4 patients). There was a side effect (moderate skin irritation) in 2 patients, but the drug was not discontinued. CONCLUSION: Results of the present study, based on its safety, effectiveness and innovative features, indicate that this combination of topical cream may be considered as a new alternative for treatment and prevention of paronychia, especially in case of occupational hand disease where prolonged treatment and continuous prevention are needed.

"Cotton nail cast": a simple solution for mild and painful lateral and distal nail embedding.

BACKGROUND: Onychocryptosis is one of the most common painful nail conditions. Conservative treatment may take a long time to obtain effective results. OBJECTIVE: The purpose of this study is to show the effectiveness of a conservative treatment of ingrown nails that shows rapid results. METHODS AND MATERIALS: Patients with painful Stage 1 to 2 onychocryptosis who were not candidates or refused surgery were treated with the cotton cast. The severity and cause of onychocryptosis was clinically evaluated during a 2-month period. A questionnaire was applied to all patients to evaluate pain, final treatment, and possible complications. RESULTS: All patients noticed results in less than 72 hours. Pain subsided in less than 24 hours in half of the patients and before 72 hours in 100% of the patients without the need of other treatments. The use of the cast prevented surgery and the accompanying morbidities in most of the patients (80%). CONCLUSION: The "cotton nail cast" is an effective conservative method for mild nail embedding. It is easy to apply, inexpensive, relieves pain rapidly, and avoids surgery in most patients.

Lapatinib side-effect management.

Lapatinib is an oral dual tyrosine kinase inhibitor targeting epidermal growth factor receptor and HER2. Diarrhea and dermatologic adverse events are reported commonly by patients treated with lapatinib. Diarrhea can range from mild to severe based on the agents used in combination with lapatinib. The adverse events may diminish quality of life, reduce treatment adherence, and lead to discontinuation of therapy. Consequently, proactive management of diarrhea is crucial, especially in patients receiving lapatinib in combination with other agents that also cause diarrhea. As the utility of lapatinib expands, crucial proactive diarrhea-management and dose-reduction strategies are evolving to decrease the likelihood of grade 3 or 4 toxicity. With regard to dermatologic adverse events, most are mild to moderate in severity, are of limited duration, and frequently do not require treatment intervention. However, in some patients, management of dermatologic adverse events is of great importance. This article reviews data regarding diarrhea and dermatologic adverse events in patients treated with lapatinib and summarizes the key role that oncology nurses play in educating patients about the potential for adverse events and the importance of preventive measures, ongoing surveillance, appropriate treatment, and dose reductions.

Herpetic whitlow: an occupational hazard.

Herpetic whitlow is a herpes infection of the digits of the hand, first described in 1909, caused by either herpes simplex virus type 1 or type 2. It was not until 1959 that herpetic whitlow was reported to occur in health care professionals. Nurse anesthetists are among the many health care professionals considered to be at high risk for acquiring herpetic whitlow, making it an occupational, but preventable, disease. After an initial infection, the virus invades the nerve tissue supplying the affected area, thus creating a reservoir for the virus to remain latent until reactivated. The recurrence of herpetic whitlow suggests that the infection persists for life. Pain, tingling and burning of the distal phalanx are the initial symptoms. Swelling and vesicles on an erythematous base follow. The infection is self-limiting, usually resolving in about three weeks. Primary infections are very inflammatory and persistent. Diagnosis can be made clinically and confirmed by many laboratory tests. Early recognition is most important, and treatment is symptomatic. The drug acyclovir has proven to be an effective chemotherapeutic agent for suppressive therapy.