First-line avelumab treatment in patients with metastatic Merkel cell carcinoma: 4-year follow-up from part B of the JAVELIN Merkel 200 study.

BACKGROUND: Results from the JAVELIN Merkel 200 study led to the approval of avelumab [an anti-programmed death-ligand 1 (PD-L1) antibody] for the treatment of metastatic Merkel cell carcinoma (mMCC) in multiple countries and its inclusion in the treatment guidelines as a preferred or recommended therapy in this setting. Here, we report 4-year follow-up results from the cohort of patients with mMCC who received avelumab as first-line treatment. PATIENTS AND METHODS: In part B of JAVELIN Merkel 200, a single-arm, open-label, phase II study, patients with mMCC who had not received prior systemic therapy for metastatic disease received avelumab 10 mg/kg via intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. In this analysis, long-term overall survival (OS), patient disposition, and subsequent treatment were analyzed. RESULTS: In total, 116 patients received first-line avelumab. At the data cutoff (2 February 2022), the median follow-up was 54.3 months (range 48.0-69.7 months). Seven patients (6.0%) remained on treatment and an additional 21 patients remained in follow-up (18.1%); 72 patients (62.1%) had died. The median OS was 20.3 months [95% confidence interval (CI) 12.4-42.0 months], with a 4-year OS rate of 38% (95% CI 29% to 47%). In patients with PD-L1+ or PD-L1- tumors, the 4-year OS rate was 48% (95% CI 26% to 67%) and 35% (95% CI 25% to 45%), respectively. In total, 48 patients (41.4%) received poststudy anticancer drug therapy, most commonly etoposide (20.7%), carboplatin (19.0%), and avelumab (12.1%). CONCLUSIONS: Avelumab first-line monotherapy in patients with mMCC resulted in meaningful long-term OS, which compared favorably with historical studies of first-line chemotherapy. These results further support the role of avelumab as a standard of care for patients with mMCC.

Evaluation of a self-questionnaire to screen for neurological complications associated with immunological checkpoint inhibitors: Are we missing something?

INTRODUCTION: Immunological checkpoint inhibitors (ICI) have led to a therapeutic revolution in the management of many cancers and indications are increasing. Neurological complications seem to have a profile quite distinct from that of toxicities related to chemotherapy, although it is possible that some manifestations remain under-reported or misdiagnosed. OBJECTIVES: (i) To evaluate the value of a self-questionnaire in screening for neurological ICI-related complications. (ii) To investigate whether, apart from the subacute complications described in the literature, neurological complications of more insidious onset might occur. METHOD: Patients followed in dermatology department for skin cancers treated with ICI, completed every infusion a neurological screening auto-questionnaire. Patients were selected for a neurological expertise based on the questionnaire's data. RESULTS: In total, 149 patients completed≥1 questionnaire, with a median delay of 174 days from the start of treatment. A total of 229 questionnaires were completed between July 2019 and December 2019. 38 patients were identified for a neurological consultation. None of these patients had a neurological event attributable to ICI. During the follow-up, only one patient had a neurological event related to ICI, which was not revealed by the questionnaire. DISCUSSION: Neurological signs in ICI-treated-skin-cancer context are more often due to tumoral progression. Neurological complications of ICI remain rare and unpredictable. The systematic neurological questionnaire has not been shown to be useful in this context. These results highlight the need to educate patients about possible subacute signs that should lead to contact the treating physicians and the need for a close cooperation between dermatologists/oncologists and neurologists.

Safety and efficacy of the anti-PD1 immunotherapy with nivolumab in trichoblastic carcinomas.

Trichoblastic carcinoma is a rare malignant cutaneous adnexal tumor with a risk of local invasion and distant metastasis. As of today, there is no consensus for the treatment of locally advanced or metastatic trichoblastic carcinoma. "AcSé Nivolumab" is a multi-center Phase II basket clinical trial (NCT03012581) evaluating the safety and efficacy of nivolumab in several cohorts of rare, advanced cancers. Here we report the results of nivolumab in patients with trichoblastic carcinoma. Of the eleven patients enrolled in the study, five patients had been previously treated by sonic hedgehog inhibitors. The primary endpoint 12-week objective response rate was 9.1% (N = 1/11) with 1 partial response. Six patients who progressed under previous lines of treatment showed stable disease at 12 weeks, reflecting a good control of the disease with nivolumab. Furthermore, 54.5% of the patients (N = 6/11) had their disease under control at 6 months. The 1-year overall survival was 80%, and the median progression-free survival was 8.4 months (95%CI, 5.7 to NA). With 2 responders (2 complete responses), the best response rate to nivolumab at any time was 18.2% (95%CI, 2.3-51.8%). No new safety signals were identified, and adverse events observed herein were previously described and well known with nivolumab monotherapy. These results are promising, suggesting that nivolumab might be an option for patients with advanced trichoblastic carcinomas. Further studies on larger cohorts are necessary to confirm these results and define the role of nivolumab in the treatment of trichoblastic carcinomas.

Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006.

BACKGROUND: Antitumor activity of ipilimumab or BRAF ± MEK inhibitors (BRAFi ± MEKi) following pembrolizumab administration in melanoma is poorly characterized. PATIENTS AND METHODS: In the phase III KEYNOTE-006 study, patients with unresectable stage III/IV melanoma received pembrolizumab (10 mg/kg) once every 2 or 3 weeks (Q3W) or ipilimumab (3 mg/kg) Q3W. The current post hoc analysis evaluates outcomes with ipilimumab or BRAFi ± MEKi as first subsequent systemic therapy after pembrolizumab administration and includes patients who completed or discontinued pembrolizumab after one or more dose. Pembrolizumab arms were pooled. RESULTS: At data cut-off (4 December 2017), median follow-up was 46.9 months. Of 555 pembrolizumab-treated patients, first subsequent therapy was ipilimumab for 103 (18.6%) and BRAFi ± MEKi for 59 (10.6%) [33 received BRAFi + MEKi, 26 BRAFi alone; 37 (62.7%) were BRAFi ± MEKi naïve]. In the subsequent ipilimumab group, ORR with previous pembrolizumab was 17.5% [1 complete response (CR); 17 partial response (PR)]; 79.6% had discontinued pembrolizumab due to progressive disease (PD); median overall survival (OS) was 21.5 months. ORR with subsequent ipilimumab was 15.5%; 11/16 responses (8 CRs; 3 PRs) were ongoing. ORR with subsequent ipilimumab was 9.7% for patients with PD as best response to pembrolizumab. Median OS from ipilimumab initiation was 9.8 months. In the subsequent BRAFi ± MEKi group, ORR with previous pembrolizumab was 13.5% (8 PR); 76.3% had discontinued pembrolizumab due to PD; median OS was 17.9 months. ORR with subsequent BRAFi ± MEKi was 30.5%, 7/18 responses (4 CR, 3 PR) were ongoing. Median OS from BRAFi ± MEKi initiation was 12.9 months. ORR for BRAFi ± MEKi-naïve patients who received subsequent BRAFi ± MEKi was 43.2%; 6/16 were ongoing (3 CR, 3 PR). CONCLUSIONS: Ipilimumab and BRAFi ± MEKi have antitumor activity as first subsequent therapy after pembrolizumab in patients with advanced melanoma.

Efficacy of sonic hedgehog inhibitors rechallenge, after initial complete response in recurrent advanced basal cell carcinoma: a retrospective study from the CARADERM database.

BACKGROUND: Smoothened (SMO) inhibitors, blocking the sonic hedgehog pathway, have been approved for advanced basal cell carcinoma (aBCC). Safety analyses reveal a high rate of adverse events (AEs) and, most of the time, vismodegib is most commonly stopped when the best overall response is reached. The long-term evolution of aBCC after vismodegib discontinuation is poorly described. The aim of this study is to evaluate the efficacy and safety of the SMO inhibitors (SMOis) available (vismodegib and sonidegib) following rechallenge after complete response (CR) following an initial treatment by vismodegib. MATERIALS AND METHODS: This real-life, retrospective, multicenter and descriptive study is based on an extraction from the CARADERM accredited database, including 40 French regional hospitals, of patients requiring BCC systemic treatment. RESULTS: Of 303 patients treated with vismodegib, 110 achieved an initial CR. The vast majority of these patients (98.2%) stopped vismodegib, notably due to poorly tolerated AEs. The CARADERM database provided a median follow-up of 21 months (13.5-36.0 months) after CR. Of the 110 patients, 48.1% relapsed after a median relapse-free survival of 24 months (13.0-38.0 months). Among them, 35 patients were retreated by an SMOi and the overall response rate was 65.7% (34.3% of CR and 31.4% of partial response). The median duration of retreatment was 6.0 months (4.0-9.5 months). CONCLUSION: Our real-life study, carried out on patients with complex clinical pictures, shows that after treatment discontinuation, 48.1% of patients achieved CR relapse within an average of 24 months (13.0-38.0 months). It emphasized that even though rechallenge can be considered as a therapeutic option, efficacy seems to decrease, suggesting the development of resistance mechanisms.

Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial.

BACKGROUND: Pembrolizumab demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile in recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). PATIENTS AND METHODS: KEYNOTE-629 was a global, open-label, nonrandomized, phase II trial of patients with locally advanced (LA) or R/M cSCC conducted at 59 centers. Eligible patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR), by blinded independent central review as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety and tolerability. Efficacy and safety were analyzed in patients who were treated with at least one dose of pembrolizumab. RESULTS: Between 29 November 2017 and 25 September 2019, 159 patients were enrolled and treated with pembrolizumab (LA cohort, n = 54; R/M cohort, n = 105). The median time from the first dose to data cut-off date (29 July 2020) was 14.9 [interquartile range (IQR), 12.6-17.2] months for the LA cohort and 27.2 (IQR, 25.6-29.2) months for the R/M cohort. In the LA cohort, ORR was 50.0% [95% confidence interval (CI), 36.1% to 63.9%], including 16.7% of patients with a CR and 33.3% with a PR. In the R/M cohort, ORR was 35.2% (95% CI, 26.2% to 45.2%), including 10.5% of patients with a CR and 24.8% with a PR. Median DOR was not reached in either cohort. Grade 3-5 treatment-related adverse events occurred in 11.9% of patients. CONCLUSIONS: The robust antitumor activity of pembrolizumab in both LA and R/M cSCC was confirmed and demonstrated to be durable without unexpected safety signals. Our findings establish pembrolizumab as a promising treatment option for cSCC.

[Mohs micrographic surgery for skin cancers: A 10 year - single-center series of 548 patients treated by formalin-fixed tissue Mohs surgery assessing the impact of reduced margins]. / Prise en charge des tumeurs cutanées selon la technique Slow Mohs « en gâteau ¼ : étude rétrospective monocentrique sur 10 ans de 548 patients évaluant l'impact de la diminution des marges.

AIM: Only few robust studies specify the indications of Mohs Surgery techniques in skin tumors. The aim of this work was to carry out a review of almost 10 years of experience, assessing the impact of reduced margins on reconstruction, and proposing a management algorithm in the light of the literature. PATIENT AND METHODS: All the records of patients having benefited from a Mohs technique in our center were retrospectively compiled from January 2011 until January 2020. A formalin-fixed tissue Mohs surgery was used. An impact assessment of reduced margins was made both on the excisional surface but also on the improvement of the reconstruction. RESULTS: 548 patients were included. Complete tumour clearance was achieved with one surgical stage in 71% of cases. The excisional surface of tumours located in the periorbital and nasal areas was significantly more often reduced compared to other areas (P=0,020). The improvement of the reconstruction was deemed significant in the periorbital and nasal areas; as well as for tumours located on limbs and trunk linked with Dermatofibrosarcoma management. CONCLUSION: This study underlines the interest of assessing the clinical relevance of reducing margins depending on the tumor location. Our single-center experience feedback on a large series allows to clarify Mohs technique indications by means of a literature review.

Real-life evaluation of the treatment of actinic keratoses by textile photodynamic therapy (FLUXMEDICARE® device).

INTRODUCTION: Actinic keratoses (AK) are a common precancerous skin condition in dermatology practice. Photodynamic therapy (PDT) with ALA or MAL is an effective but painful treatment of fields of cancerization particularly when conventional illumination sources and irradiation rates are used. Two prior studies showed that illumination with textile PDT was not inferior to conventional PDT. FLUXMEDICARE® (FLX-PDT) is the first medical device marketed with textile based lighting . We performeda real-life study to evaluate efficacy and tolerance of this device. METHODS: We carried out a single-center retrospective study. We collected data from patients treated with FLX-PDT with MAL for AKs localized on scalp and temples between November 2018 and November 2019. The primary endpoint was complete clearance rate (CR) at 3 months-follow up. RESULTS: Data of 39 patients were reviewed in the study, with a total of 417 AKs. The CR rate was 72.6 % (95 %CI 67.9-77.0) at 3 months-follow up and 67.5 % (95 %CI 61.2-73.3) at 6 months-follow up. The median pain felt during the session was 0 and there wasn't erythema after the session for 64.1 %. CONCLUSION: Our real-life study confirms efficacy and safety of textile PDT by FLUXMEDICARE device in the treatment of scalp and temples AKs, with excellent tolerance and minimal pain reported.

Relevance of body mass index as a predictor of systemic therapy outcomes in metastatic melanoma: analysis of the MelBase French cohort data☆.

BACKGROUND: The 'obesity paradox' suggests that higher body mass index (BMI) is associated with better survival values in metastatic melanoma patients, especially those receiving targeted and immune checkpoint inhibitor therapy. Higher BMI is also associated with higher incidences of treatment-related adverse events (TRAEs). This study assesses whether BMI is associated with survival outcomes and adverse events in metastatic melanoma patients with systemic therapy. PATIENTS AND METHODS: This multicentric retrospective study, conducted from 1 March 2013 to 29 April 2019, enrolled adults with unresectable stage III or IV melanoma from the French multicentric prospective cohort-MelBase (NCT02828202). Patients with first-line chemotherapy and targeted and immune therapy were included. Underweight people and those with metastatic mucosal or ocular melanoma were excluded. BMI was categorized using the World Health Organization criteria. Co-primary outcomes included the association between BMI and progression-free survival and overall survival, stratified by treatment type, sex, and age. Secondary endpoints were the association of BMI with overall response and TRAEs. Multivariate analyses were carried out. RESULTS: A total of 1214 patients were analyzed. Their median age was 66.0 years (range, 53-75). Male predominance was observed [n = 738 (61%)]. Most patients received immune checkpoint inhibitor therapy (63%), followed by targeted therapy (32%), and had stage M1c disease (60.5%). Obese patients represented 22% of the cohort. The median follow-up duration was 13.5 months (range, 6.0-27.5). In the pooled analysis, no positive or negative association between BMI and progression-free survival (P = 0.88)/overall survival (P = 0.25) was observed, regardless of treatment type, sex, and age. These results were nonsignificant in the univariate and multivariate analyses. The objective response rate, according to BMI category, did not differ significantly regardless of age. TRAEs were not associated with BMI. CONCLUSION: The observed lack of an association between BMI and survival demonstrates that BMI is not a valuable marker of systemic treatment-related outcomes in metastatic melanoma. Future approaches might focus on the whole-body distribution.

Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry.

BACKGROUND: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. OBJECTIVES: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. METHODS: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. RESULTS: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. CONCLUSIONS: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.

The conventional protocol vs. a protocol including illumination with a fabric-based biophotonic device (the Phosistos protocol) in photodynamic therapy for actinic keratosis: a randomized, controlled, noninferiority clinical study.

BACKGROUND: Topical photodynamic therapy (PDT) using methyl aminolaevulinate is a noninvasive treatment option suitable to treat clinical and subclinical actinic keratosis (AK) over a large area (field cancerization). The most widely used, conventional protocol in Europe includes illumination with a red-light lamp. This illumination commonly causes pain, and patients often cannot complete the treatment. OBJECTIVES: The aims of this paper are twofold. The first aim is to introduce a novel protocol, the Phosistos protocol (P-PDT), which includes illumination with a fabric-based biophotonic device. The second and major aim is to assess the noninferiority, in terms of efficacy for PDT of AK, of P-PDT compared with the conventional protocol (C-PDT). METHODS: A randomized, controlled, multicentre, intraindividual clinical study was conducted. Forty-six patients with grade I-II AK of the forehead and scalp were treated with P-PDT on one area (280 AK lesions) and with C-PDT on the contralateral area (280 AK lesions). The primary end point was the lesion complete response (CR) rate at 3 months, with an absolute noninferiority margin of -10%. Secondary end points included pain scores, incidence of adverse effects and cosmetic outcome. RESULTS: Three months following treatment, the lesion CR rate of P-PDT was noninferior to that of C-PDT (79·3% vs. 80·7%, respectively; absolute difference -1·6%; one-sided 95% confidence interval -4·5% to infinity). The noninferiority of P-PDT to C-PDT in terms of the lesion CR rate remained at the 6-month follow-up (94·2% vs. 94·9%, respectively; absolute difference -0·6%; one-sided 95% confidence interval -2·7% to infinity). Moreover, the pain score at the end of illumination was significantly lower for P-PDT than for C-PDT (mean ± SD 0·3 ± 0·6 vs. 7·4 ± 2·3; P < 0·001). CONCLUSIONS: P-PDT is noninferior to C-PDT in terms of efficacy for treating AK of the forehead and scalp and resulted in much lower pain scores and fewer adverse effects. What's already known about this topic? Topical photodynamic therapy using methyl aminolaevulinate is effective for treating actinic keratosis. In Europe, the conventional protocol involves illumination with a red-light lamp. Unfortunately, pain is often experienced by patients undergoing this protocol. An alternative protocol that uses daylight illumination has recently been shown to be as effective as the conventional protocol while being nearly painless. However, this alternative protocol can be conducted only in suitable weather conditions. What does this study add? The Phosistos protocol is demonstrated to be as effective as the conventional protocol, nearly as painless as the daylight protocols and suitable year round for treatment of actinic keratosis.

[Stage III melanoma: Sentinel node biopsy, completion lymph node dissection and prospects of adjuvant therapy. A French national survey on current and envisaged practices]. / Mélanome au stade ganglionnaire : analyse du ganglion sentinelle, curage ganglionnaire, perspective des traitements adjuvants. Enquête nationale française sur les pratiques actuelles et envisagées.

BACKGROUND: The recent publication of randomized trials investigating the efficacy of adjuvant therapy and completion lymph node dissection at microscopic stage III melanoma calls for a reappraisal of melanoma management from different angles: indications for sentinel lymph node biopsy, indications for completion lymph node dissection in microscopic-stage disease, and adjuvant therapies. Our objective was to evaluate current practices and to question French onco-dermatologists about any changes they envisaged in their practices in the light of recent publications. METHODS: We conducted a national survey among members of the Cutaneous Oncology Group of the French Society of Dermatology in October 2017. RESULTS: Forty French health centers were included, and 53 individual responses were collected. Sentinel lymph node biopsy for melanoma was performed at 75 % of the centers. Before the summer of 2017 and the publication of MSLT-II (proving the absence of any therapeutic benefits for complete lymph node dissection in microscopic stage III melanoma), when a positive sentinel lymph node was diagnosed, immediate completion lymph node dissection was performed at 90 % of the centers. After the publication of MSLT-II, 45 % of the respondents considered stopping this practice. The risk-benefit ratio prompted prescription of nivolumab and of combined dabrafenib+trametinib as adjuvant therapy by respectively 96 % and 79 % of respondents, while the corresponding rates for interferon and ipilimumab were only 21 % and 15 %. CONCLUSION: Early melanoma management stands on the verge of major changes thanks to the arrival of efficient adjuvant therapies and a decrease in immediate completion lymph node dissections for patients with microscopic stage III is also anticipated.

[Creation, implementation and objectives of CARADERM, a national network for rare skin carcinomas - Adnexal neoplasm part]. / Développement, mise en œuvre et objectifs de CARADERM, réseau national cancers cutanés rares ­ partie carcinomes annexiels.

INTRODUCTION: CARADERM is a French national network that includes patients with rare skin adnexal neoplasms. The present paper describes only the adnexal neoplasm part of this network. The primary objective of CARADERM is to improve medical care for malignant skin adnexal neoplasms. A multidisciplinary review group and a centralized pathological review group have been set up. PATIENTS AND METHODS: A dual network of clinicians and pathologists has been set up. Data are recorded in a secure database. RESULTS: The CARADERM network comprises of 38 clinical centres and 22 pathology centres. Between 2014 and 2017, 1598 patients with an adnexal neoplasm were included. Data of interest were documented in 80% of cases. Median patient age was 72 years. Major histological subtypes were sweat gland carcinomas (50%), hair follicle carcinomas (37.7%), and sebaceous gland carcinomas (9.8%). Surgery was the first-line treatment for 81% of patients, including 76.9% with standard surgical margin analysis, and 5.5% with exhaustive margin analysis. 920 patients (57.6%) underwent a national pathology review process. DISCUSSION: The CARADERM network aims at providing assistance in difficult situations concerning diagnosis and care in skin adnexal neoplasms. Analysis of the CARADERM data should allow the creation of a prognostic classification of these rare neoplasms together with recommendations. A national multidisciplinary consensus exists. Translational and therapeutic research is ongoing. CONCLUSION: The CARADERM network is currently recruiting and more data should lead to improved knowledge of these tumours in the coming years.

[Primitive myxoid melanoma: An unusual histological aspect]. / Mélanome myxoïde primitif : une forme histologique inhabituelle.

BACKGROUND: Myxoid melanoma is a rare variant of melanoma that must be recognised. Herein we describe a new metastatic case. PATIENTS AND METHODS: A 78-year-old woman consulted for a firm, pinkish nodule measuring 25mm and present for six months on her left leg. Analysis of the biopsy revealed achromic fusiform tumour cells separated by large myxoid plaques. Labeling of SOX10, HMB45 and PS100 was diffuse and of moderate to strong intensity. A diagnosis of myxoid melanoma was considered, with Breslow thickness of 9mm. Surgery was carried out with a 2-cm margin and confirmed the diagnosis. Dermatological follow-up at one year revealed metastatic spread to the ganglia, pleura, liver and bone. DISCUSSION: Few cases of primary myxoid melanoma have been described, and the condition is probably underdiagnosed. The classic clinical presentation of this condition consists of a solitary achromic nodule found chiefly on the limbs. The microscopic appearance is relatively non-specific. Immunohistochemical analysis may indicate melanocytic involvement: cells exhibit expression of SOX10, diffuse expression of protein S100, and less consistent and more variable expression of HMB45. The increasingly common use of anti-SOX10 is of value since it is expressed in the nucleus of melanocytes. Mastocytes and TGF-ß secretion appear to be involved in myxoid stroma production. In the absence of specific codification, management of myxoid melanoma is comparable to that of other types of melanoma. There is uncertainty about the prognosis, with the involvement of TGF-ß possibly indicating the aggressive potential of this type of tumour.

Photodynamic therapy for actinic keratosis of the forehead and scalp: a randomized, controlled, phase II clinical study evaluating the noninferiority of a new protocol involving irradiation with a light-emitting, fabric-based device (the Flexitheralight protocol) compared with the conventional protocol involving irradiation with the Aktilite CL 128 lamp.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK), particularly for patients with large areas of field cancerization. Among the approved protocols in Europe, the most widely used requires irradiation with the Aktilite CL 128 lamp. However, pain during irradiation and the suboptimal adaptability of the lamp relative to the treatment area are two limiting factors of this protocol. To overcome these limits, a new protocol (referred to as the Flexitheralight protocol) involving irradiation with a light-emitting, fabric-based device was developed. OBJECTIVES: This paper aims to assess the noninferiority, in terms of PDT efficacy for treating AK, of the Flexitheralight protocol compared with the conventional protocol, which requires irradiation with the Aktilite CL 128 lamp. METHODS: A monocentric, randomized, controlled, phase II clinical study was performed. Twenty-five patients with grade I-II AKs of the forehead and scalp were treated with methyl aminolaevulinate PDT in two symmetrical areas. One area was treated with the conventional protocol (n = 154 AKs), whereas the other area was treated with the Flexitheralight protocol (n = 156 AKs). The primary end-point was the lesion complete response (CR) rate at 3 months (an absolute noninferiority margin of -10% was used). The secondary end-points included patient-reported pain at the end of the irradiation. RESULTS: At 3 months, the lesion CR rate with the Flexitheralight protocol was noninferior to that obtained with the conventional protocol (66·0% vs. 59·1%, respectively; absolute difference, 6·9%; 95% confidence interval -0·6% to 14·5%). Patient-reported pain was significantly lower with the Flexitheralight protocol than with the conventional protocol (mean ± SD: 0·4 ± 0·6 vs. 5·0 ± 2·6; P < 0·0001). CONCLUSIONS: The Flexitheralight protocol is noninferior in terms of efficacy and superior in terms of tolerability to the conventional protocol for treating AKs of the forehead and scalp.