- Email: [email protected]
Management of high-risk squamous cell carcinoma
2013
1497
Initial experience of electronic brachytherapy for the treatment of 508 nonmelanoma skin cancer (NMSC) lesions in 305 patients Robert Strimling, MD, Strimling Dermatology, Laser and Vein Institute, Las Vegas, NV, United States; Camtu Lee Jones, MD, Strimling Dermatology, Laser and Vein Institute, Las Vegas, NV, United States; Jason Schaeffer, Strimling Dermatology, Laser and Vein Institute, Las Vegas, NV, United States; Shawneca Beckum, Strimling Dermatology, Laser and Vein Institute, Las Vegas, NV, United States Purpose/objective(s): To evaluate the acute adverse effects and early cosmetic outcomes of patients treated with electronic brachytherapy for the treatment of cutaneous malignancies. Procedure/study: From April 2013 to August 2014, 305 patients with 508 cutaneous malignancies were treated with HDR Electronic Brachytherapy system using surface applicators to a dose of 40.0 Gy in 8 equal fractions, delivered twice weekly with a minimum interval of 48 hours. The appropriately sized surface applicator, 10 mm, 20 mm, 35 mm, or 50 mm, was selected to allow for complete coverage of the target lesion with acceptable margin. Pretreatment biopsy confirmed diagnosis. Lesion depth was clinically assessed. The prescription depth was 0-5 mm, 0 mm for 19.9% of the lesions, 1 mm for 50.4% of the lesions, and 2 mm for 24.4% of the lesions (total 94.7%).Photographs were taken for all patients at initial consultation, completion of treatment and follow-up visits. Acute safety outcomes and cosmetic results were analyzed.
Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: 30-month final update of the pivotal ERIVANCE BCC study Aleksandar Sekulic, Mayo Clinic, Scottsdale, AZ, United States; Michael R. Migden, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; Nicole Basset-Seguin, H^ opital Saint-Louis, Paris, France; Claus Garbe, Universit€atsklinikum T€ ubingen, T€ ubingen, Germany; Anja Gesierich, Universit€atsklinikum W€ urzburg, W€ urzburg, Germany; Christopher Lao, University of Michigan, Ann Arbor, MI, United States; Christopher J. Miller, Hospital of the University of Pennsylvania, Philadelphia, PA, United States; Laurent Mortier, Center Hospitalier Regional Universitaire de Lille, Lille, France; Dedee F, Murrell, Premier Specialists, University of New South Wales, Sydney, Australia; Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles, CA, United States; Jorge Fernando Quevedo, Mayo Clinic, Rochester, MN, United States; Jeannie Hou, Genentech, Inc, South San Francisco, CA, United States; Mukta Tripathi, Genentech, Inc, South San Francisco, CA, United States
Results: 285 skin lesions were basal cell carcinoma, 223 were squamous cell carcinoma. 55 lesions were located on the nose, 27 on the ear, 190 on the face, 39 on the scalp, 51 on the torso, and 146 on the extremities. Median follow-up was 3.26 months (range, 0-15). 22.8% developed radiation dermatitis grade 1 or 2 during treatment, which resolved by the 3 month visit at the latest. There were no severe (grade 3 or higher) acute toxicities. Fifty-two patients developed moist desquamation during treatment which resolved at 2-3 month follow-up. Twenty-seven patients developed hypopigmentation at 1 month, and 3 patients developed hypopigmentation at 10 months. The vast majority of patients have been satisfied with the Xoft experience and happy with their cosmetic outcome. For most of these patients, Xoft treatments were painless and without visible or unacceptable scarring. However, some patients have been dissatisfied with pain associated with radiodermatitis both during and after the treatment course and/or healing associated with hypopigmentation or scarring. There was evidence of one tumor recurrence identified at the edge of treatment field. Conclusions: The early outcomes of electronic brachytherapy for the treatment of nonmelanoma skin cancer (NMSC) appear to show acceptable acute toxicities and favorable early cosmesis. The early results seem comparable to high dose rate brachytherapy. The hypofractionated approach provides patient convenience with effective early outcomes. Long term follow-up is being collected to further assess efficacy and cosmesis. Sponsored by Xoft a subsidiary of iCAD, Inc.
Background: Vismodegib (VISMO), the first Hedgehog pathway inhibitor to be FDA approved, provides a treatment option for patients (pts) with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC). In the pivotal ERIVANCE BCC trial, VISMO showed objective response rates (ORRs) by independent review of 30% in mBCC and 43% in laBCC. ORRs by investigator (INV) review were 45% (mBCC) and 60% (laBCC), with median duration of response (DOR) of 12.9 and 7.6 months (mo), respectively. We present safety and INV-assessed efficacy results 30 mo (May 30, 2013) after primary analysis (November 26, 2010). Methods: ERIVANCE BCC was a multicenter, international, nonrandomized study in pts (N ¼ 104) with radiographically measurable mBCC or laBCC (surgery inappropriate because of multiple recurrence, or substantial morbidity or deformity anticipated) receiving oral VISMO 150 mg once daily until disease progression or intolerable toxicity. Secondary endpoints included INV-ORR, DOR, progression-free survival (PFS), overall survival (OS), and safety. Exploratory analysis investigated whether pt subsets (demographics, baseline characteristics, and region) had a differential treatment effect. Results: At data cutoff, 8 pts were receiving study drug and continued to undergo protocol assessments (69 pts in survival follow-up). ORR (INV) was 48.5% in mBCC (all partial responses [PR]) and 60.3% in laBCC (20 complete responses and 18 PR). Median DOR (INV) improved from 12.9 and 7.6 mo for mBCC and laBCC (primary analysis) to 14.8 and 26.2 mo, respectively. Median PFS (INV) (95% CI) was 9.3 (7.416.6) mo in mBCC and 12.9 (10.2-28.0) mo in laBCC. Median PFS was higher in pts with laBCC vs pts with mBCC in each of the pt subgroups, except those with ECOG PS 1 and target lesions at baseline of 1 and 3. OS for mBCC was 33.4 (18.1-not estimable) mo and not reached in laBCC. Adverse events remained consistent with the primary analysis; [30% of pts reported muscle spasm, alopecia, dysgeusia, weight decrease, fatigue, and nausea. 17 deaths were reported since the primary analysis; they were not considered drug related and occurred in survival follow-up. Conclusion: The 30-month ERIVANCE BCC update further demonstrated the durable response first reported in the primary analyses and showed long-term safety of VISMO in pts with aBCC. Funded by Roche-Genentech.
1167 Longitudinal safety modeling and simulation for optimization of vismodegib treatment interruption in a phase 2 study of operable basal cell carcinoma (BCC) Howard Sofen, UCLA School of Medicine, Los Angeles, CA, United States; Tong Lu, Genentech/Roche, South San Francisco, CA, United States; Ivor Caro, Genentech/Roche, South San Francisco, CA, United States; Jin Jin, Genentech/Roche, South San Francisco, CA, United States Background: Vismodegib (VISMO), the first FDA-approved Hedgehog pathway inhibitor, is indicated for adults with metastatic or locally advanced BCC that has recurred after surgery or who are not candidates for surgery and radiation; it provides a new treatment option for patients (pts) with advanced BCC. Most common adverse drug reactions (ADR) ([30%) included muscle spasms, alopecia, dysgeusia, weight loss, fatigue, and nausea. To explore the effect of VISMO treatment interruption/discontinuation (I/D) on the ADRs including muscle spasms and dysgeusia/ageusia, we used longitudinally ordered categorical models in a phase 2 study with varying treatment durations and follow-up in pts with operable BCC. Methods: Pts received VISMO (150 mg QD): cohort (C) 1, 12 weeks (wks); C2, 12 wks with 24 wks observation (obs); or C3, 8 wks with 4 wks obs then 8 wks. Individual pharmacokinetic (PK) profiles for unbound VISMO were predicted based on a previous population PK model incorporating individual covariates and used in this PK/AE analysis in NONMEM (Laplacian method). Results: 24 pts enrolled in C1, 25 in C2, and 25 in C3. 24 pts in each cohort reported any AEs, the most frequently reported including: C1, muscle spasms (19 pts; 79%), ageusia (10 pts; 42%), dysgeusia (9 pts; 38%), and alopecia (8 pts; 33%); C2, muscle spasms (19 pts; 76%), alopecia (17 pts; 68%), and dysgeusia (13 pts; 52%); C3, muscle spasms (18 pts; 72%), alopecia (18 pts; 72%), and dysgeusia (15 pts; 60%). The median duration was around 20 days for muscle spasm and 35 days for dysgeusia/ageusia. Simulations showed that after 12 wks of VISMO, 6 wks of I/D could lead to complete resolution of all grades of muscle spasm in 80% of pts and 4 wks of I/D could lead to significant improvement without grade ¼ 2 muscle spasms in 95% of pts. For dysgeusia/ageusia, a 12-wk I/D could lead to complete resolution of all grades of dysgeusia/ageusia in 80% of pts, and a 6-wk I/D could lead to a significant improvement without grade ¼ 2 dysgeusia/ageusia in 95% of pts. Conclusion: Longitudinal PK/PD modeling indicates that treatment I/D may help resolve ADRs typically associated with VISMO. Such data may enable the optimization of VISMO treatment interruption. Funded by Roche-Genentech.
MAY 2015
555 Management of high-risk squamous cell carcinoma Pallavi Gupta, MBBS, Monklands Hospital, Lanarkshire Center for Dermatology, Airdrie, United Kingdom; Girish Gupta, MBChB, Monklands Hospital, Lanarkshire Center for Dermatology, Airdrie, United Kingdom Background: Management of primary cutaneous squamous cell carcinoma (SCC) in Scotland is in accordance with guidelines published by Scottish Intercollegiate Guidelines Network (SIGN) in 2006 and updated in 2014. These recommend that primary excision is the criterion standard for management of SCC. Patients with SCC should have an assessment of high-risk features and be discussed at multidisciplinary meetings (MDT). Aim: To review the management of all SCCs, in particular those with high-risk features and to investigate if management was appropriate and in accordance with SIGN guidelines. Methods: A retrospective review of a total of 211 patients with SCC who were discussed at the MDT in Lanarkshire, Scotland in 2012 and 2013. Results: The majority of SCCs, 161 of 211 (76%), were treated with primary excision and 50 of 211 (24 %) SCCs were treated with curettage and cautery (C+C). 146 (69%) SCCs were completely excised and 65 (31%) tumors were excised incompletely. Of the 65 incomplete excisions, 44 (68%) resulted from C+C and 21 (32%) from primary excision. Of the 211 SCCs, 105 (50%) displayed high-risk features. 80 of 105 (76%) high-risk SCCs were treated by primary excision and 25 (24%) with C+C. Of the 105 high-risk SCCs, 67 (64%) were completely excised and the rest (36%) were excised incompletely. MDT recommendation in 61 of 105 (58%) high-risk SCCs was for further intervention in the form of wide local excision (WLE) or radiotherapy (XRT) and clinical observation in 44 of 105 (42%) cases. 13 of 105 (12.5%) high-risk SCCs treated with primary excision were incompletely excised, and further intervention in the form WLE or WLE 6 XRT was recommended for all of these patients. 25 of 105 (24%) high-risk tumors treated with primary C+C were incompletely excised, of which WLE or WLE and XRT was recommended in 13 (12.5%) and clinical observation in 12 (12%) cases. Conclusion: This study highlights the significant number of SCCs displaying highrisk features. The majority of SCCs were treated appropriately in accordance with the SIGN guidelines. MDT proformas and pathology reports were generally robust; however there was scope for more detailed data gathering to accurately grade tumors. Most incompletely excised high-risk SCCs underwent further surgery. However, a small proportion was managed by clinical observation. Commercial support: None identified.
J AM ACAD DERMATOL
AB187
1497
Initial experience of electronic brachytherapy for the treatment of 508 nonmelanoma skin cancer (NMSC) lesions in 305 patients Robert Strimling, MD, Strimling Dermatology, Laser and Vein Institute, Las Vegas, NV, United States; Camtu Lee Jones, MD, Strimling Dermatology, Laser and Vein Institute, Las Vegas, NV, United States; Jason Schaeffer, Strimling Dermatology, Laser and Vein Institute, Las Vegas, NV, United States; Shawneca Beckum, Strimling Dermatology, Laser and Vein Institute, Las Vegas, NV, United States Purpose/objective(s): To evaluate the acute adverse effects and early cosmetic outcomes of patients treated with electronic brachytherapy for the treatment of cutaneous malignancies. Procedure/study: From April 2013 to August 2014, 305 patients with 508 cutaneous malignancies were treated with HDR Electronic Brachytherapy system using surface applicators to a dose of 40.0 Gy in 8 equal fractions, delivered twice weekly with a minimum interval of 48 hours. The appropriately sized surface applicator, 10 mm, 20 mm, 35 mm, or 50 mm, was selected to allow for complete coverage of the target lesion with acceptable margin. Pretreatment biopsy confirmed diagnosis. Lesion depth was clinically assessed. The prescription depth was 0-5 mm, 0 mm for 19.9% of the lesions, 1 mm for 50.4% of the lesions, and 2 mm for 24.4% of the lesions (total 94.7%).Photographs were taken for all patients at initial consultation, completion of treatment and follow-up visits. Acute safety outcomes and cosmetic results were analyzed.
Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: 30-month final update of the pivotal ERIVANCE BCC study Aleksandar Sekulic, Mayo Clinic, Scottsdale, AZ, United States; Michael R. Migden, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; Nicole Basset-Seguin, H^ opital Saint-Louis, Paris, France; Claus Garbe, Universit€atsklinikum T€ ubingen, T€ ubingen, Germany; Anja Gesierich, Universit€atsklinikum W€ urzburg, W€ urzburg, Germany; Christopher Lao, University of Michigan, Ann Arbor, MI, United States; Christopher J. Miller, Hospital of the University of Pennsylvania, Philadelphia, PA, United States; Laurent Mortier, Center Hospitalier Regional Universitaire de Lille, Lille, France; Dedee F, Murrell, Premier Specialists, University of New South Wales, Sydney, Australia; Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles, CA, United States; Jorge Fernando Quevedo, Mayo Clinic, Rochester, MN, United States; Jeannie Hou, Genentech, Inc, South San Francisco, CA, United States; Mukta Tripathi, Genentech, Inc, South San Francisco, CA, United States
Results: 285 skin lesions were basal cell carcinoma, 223 were squamous cell carcinoma. 55 lesions were located on the nose, 27 on the ear, 190 on the face, 39 on the scalp, 51 on the torso, and 146 on the extremities. Median follow-up was 3.26 months (range, 0-15). 22.8% developed radiation dermatitis grade 1 or 2 during treatment, which resolved by the 3 month visit at the latest. There were no severe (grade 3 or higher) acute toxicities. Fifty-two patients developed moist desquamation during treatment which resolved at 2-3 month follow-up. Twenty-seven patients developed hypopigmentation at 1 month, and 3 patients developed hypopigmentation at 10 months. The vast majority of patients have been satisfied with the Xoft experience and happy with their cosmetic outcome. For most of these patients, Xoft treatments were painless and without visible or unacceptable scarring. However, some patients have been dissatisfied with pain associated with radiodermatitis both during and after the treatment course and/or healing associated with hypopigmentation or scarring. There was evidence of one tumor recurrence identified at the edge of treatment field. Conclusions: The early outcomes of electronic brachytherapy for the treatment of nonmelanoma skin cancer (NMSC) appear to show acceptable acute toxicities and favorable early cosmesis. The early results seem comparable to high dose rate brachytherapy. The hypofractionated approach provides patient convenience with effective early outcomes. Long term follow-up is being collected to further assess efficacy and cosmesis. Sponsored by Xoft a subsidiary of iCAD, Inc.
Background: Vismodegib (VISMO), the first Hedgehog pathway inhibitor to be FDA approved, provides a treatment option for patients (pts) with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC). In the pivotal ERIVANCE BCC trial, VISMO showed objective response rates (ORRs) by independent review of 30% in mBCC and 43% in laBCC. ORRs by investigator (INV) review were 45% (mBCC) and 60% (laBCC), with median duration of response (DOR) of 12.9 and 7.6 months (mo), respectively. We present safety and INV-assessed efficacy results 30 mo (May 30, 2013) after primary analysis (November 26, 2010). Methods: ERIVANCE BCC was a multicenter, international, nonrandomized study in pts (N ¼ 104) with radiographically measurable mBCC or laBCC (surgery inappropriate because of multiple recurrence, or substantial morbidity or deformity anticipated) receiving oral VISMO 150 mg once daily until disease progression or intolerable toxicity. Secondary endpoints included INV-ORR, DOR, progression-free survival (PFS), overall survival (OS), and safety. Exploratory analysis investigated whether pt subsets (demographics, baseline characteristics, and region) had a differential treatment effect. Results: At data cutoff, 8 pts were receiving study drug and continued to undergo protocol assessments (69 pts in survival follow-up). ORR (INV) was 48.5% in mBCC (all partial responses [PR]) and 60.3% in laBCC (20 complete responses and 18 PR). Median DOR (INV) improved from 12.9 and 7.6 mo for mBCC and laBCC (primary analysis) to 14.8 and 26.2 mo, respectively. Median PFS (INV) (95% CI) was 9.3 (7.416.6) mo in mBCC and 12.9 (10.2-28.0) mo in laBCC. Median PFS was higher in pts with laBCC vs pts with mBCC in each of the pt subgroups, except those with ECOG PS 1 and target lesions at baseline of 1 and 3. OS for mBCC was 33.4 (18.1-not estimable) mo and not reached in laBCC. Adverse events remained consistent with the primary analysis; [30% of pts reported muscle spasm, alopecia, dysgeusia, weight decrease, fatigue, and nausea. 17 deaths were reported since the primary analysis; they were not considered drug related and occurred in survival follow-up. Conclusion: The 30-month ERIVANCE BCC update further demonstrated the durable response first reported in the primary analyses and showed long-term safety of VISMO in pts with aBCC. Funded by Roche-Genentech.
1167 Longitudinal safety modeling and simulation for optimization of vismodegib treatment interruption in a phase 2 study of operable basal cell carcinoma (BCC) Howard Sofen, UCLA School of Medicine, Los Angeles, CA, United States; Tong Lu, Genentech/Roche, South San Francisco, CA, United States; Ivor Caro, Genentech/Roche, South San Francisco, CA, United States; Jin Jin, Genentech/Roche, South San Francisco, CA, United States Background: Vismodegib (VISMO), the first FDA-approved Hedgehog pathway inhibitor, is indicated for adults with metastatic or locally advanced BCC that has recurred after surgery or who are not candidates for surgery and radiation; it provides a new treatment option for patients (pts) with advanced BCC. Most common adverse drug reactions (ADR) ([30%) included muscle spasms, alopecia, dysgeusia, weight loss, fatigue, and nausea. To explore the effect of VISMO treatment interruption/discontinuation (I/D) on the ADRs including muscle spasms and dysgeusia/ageusia, we used longitudinally ordered categorical models in a phase 2 study with varying treatment durations and follow-up in pts with operable BCC. Methods: Pts received VISMO (150 mg QD): cohort (C) 1, 12 weeks (wks); C2, 12 wks with 24 wks observation (obs); or C3, 8 wks with 4 wks obs then 8 wks. Individual pharmacokinetic (PK) profiles for unbound VISMO were predicted based on a previous population PK model incorporating individual covariates and used in this PK/AE analysis in NONMEM (Laplacian method). Results: 24 pts enrolled in C1, 25 in C2, and 25 in C3. 24 pts in each cohort reported any AEs, the most frequently reported including: C1, muscle spasms (19 pts; 79%), ageusia (10 pts; 42%), dysgeusia (9 pts; 38%), and alopecia (8 pts; 33%); C2, muscle spasms (19 pts; 76%), alopecia (17 pts; 68%), and dysgeusia (13 pts; 52%); C3, muscle spasms (18 pts; 72%), alopecia (18 pts; 72%), and dysgeusia (15 pts; 60%). The median duration was around 20 days for muscle spasm and 35 days for dysgeusia/ageusia. Simulations showed that after 12 wks of VISMO, 6 wks of I/D could lead to complete resolution of all grades of muscle spasm in 80% of pts and 4 wks of I/D could lead to significant improvement without grade ¼ 2 muscle spasms in 95% of pts. For dysgeusia/ageusia, a 12-wk I/D could lead to complete resolution of all grades of dysgeusia/ageusia in 80% of pts, and a 6-wk I/D could lead to a significant improvement without grade ¼ 2 dysgeusia/ageusia in 95% of pts. Conclusion: Longitudinal PK/PD modeling indicates that treatment I/D may help resolve ADRs typically associated with VISMO. Such data may enable the optimization of VISMO treatment interruption. Funded by Roche-Genentech.
MAY 2015
555 Management of high-risk squamous cell carcinoma Pallavi Gupta, MBBS, Monklands Hospital, Lanarkshire Center for Dermatology, Airdrie, United Kingdom; Girish Gupta, MBChB, Monklands Hospital, Lanarkshire Center for Dermatology, Airdrie, United Kingdom Background: Management of primary cutaneous squamous cell carcinoma (SCC) in Scotland is in accordance with guidelines published by Scottish Intercollegiate Guidelines Network (SIGN) in 2006 and updated in 2014. These recommend that primary excision is the criterion standard for management of SCC. Patients with SCC should have an assessment of high-risk features and be discussed at multidisciplinary meetings (MDT). Aim: To review the management of all SCCs, in particular those with high-risk features and to investigate if management was appropriate and in accordance with SIGN guidelines. Methods: A retrospective review of a total of 211 patients with SCC who were discussed at the MDT in Lanarkshire, Scotland in 2012 and 2013. Results: The majority of SCCs, 161 of 211 (76%), were treated with primary excision and 50 of 211 (24 %) SCCs were treated with curettage and cautery (C+C). 146 (69%) SCCs were completely excised and 65 (31%) tumors were excised incompletely. Of the 65 incomplete excisions, 44 (68%) resulted from C+C and 21 (32%) from primary excision. Of the 211 SCCs, 105 (50%) displayed high-risk features. 80 of 105 (76%) high-risk SCCs were treated by primary excision and 25 (24%) with C+C. Of the 105 high-risk SCCs, 67 (64%) were completely excised and the rest (36%) were excised incompletely. MDT recommendation in 61 of 105 (58%) high-risk SCCs was for further intervention in the form of wide local excision (WLE) or radiotherapy (XRT) and clinical observation in 44 of 105 (42%) cases. 13 of 105 (12.5%) high-risk SCCs treated with primary excision were incompletely excised, and further intervention in the form WLE or WLE 6 XRT was recommended for all of these patients. 25 of 105 (24%) high-risk tumors treated with primary C+C were incompletely excised, of which WLE or WLE and XRT was recommended in 13 (12.5%) and clinical observation in 12 (12%) cases. Conclusion: This study highlights the significant number of SCCs displaying highrisk features. The majority of SCCs were treated appropriately in accordance with the SIGN guidelines. MDT proformas and pathology reports were generally robust; however there was scope for more detailed data gathering to accurately grade tumors. Most incompletely excised high-risk SCCs underwent further surgery. However, a small proportion was managed by clinical observation. Commercial support: None identified.
J AM ACAD DERMATOL
AB187