- Email: [email protected]
Real life use of talimogene laherparepvec in melanoma in centers in Austria and Switzerland
abstracts
Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution): Immunocore; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Millennium; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Physiomics; Advisory / Consultancy, Research grant / Funding (institution): Rigontec; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Vertex; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution): Immunocore; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Millennium; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Physiomics; Advisory / Consultancy, Research grant / Funding (institution): Rigontec; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Vertex. K. Harrington: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD. M. Ross: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck ; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen. K. Ohrling: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. H. Radcliffe: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. F. Collichio: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck.
v548 | Melanoma and other skin tumours
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Real life use of talimogene laherparepvec in melanoma in centers in Austria and Switzerland
C. Hoeller1, J.M. Ressler1, M. Karasek2, V. Aedo Lopez3, L. Koch4, H. Kehrer5, P. Koelblinger6, F. Weihsengruber7, J. Kofler8, E. Richtig9, O.A. Michielin10, C. Hafner11 1 Department of Dermatology, Medizinische Universitaet Wien (Medical University of Vienna), Vienna, Austria, 2Department of Dermatology, University Hospital St. Poelten, St. Poelten, Austria, 3Service d’Oncologie, CHUV - Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 4Department of Dermatology, Medical University of Graz, Graz, Austria,5Department of Dermatology, Krankenhaus der Elisabethinen, Linz, Austria, 6Department of Dermatology, Paracelsus Medical University, Salzburg, Austria, 7 Department of Dermatology and Venerology, Krankenanstalt Rudolfstiftung, Vienna, Austria, 8Department of Dermatology, Landeskrankenhaus LKH Klagenfurt am Woerthersee, Klagenfurt, Austria, 9Department of Dermatology, Institute of Pathology, Medical University of Graz, Graz, Austria, 10Oncology, Centre Hospitalier Universitaire Vaudois - CHUV, Lausanne, Switzerland, 11Department of Dermatology, University Hospital St. Po¨lten, Karl Landsteiner University of Health Sciences, St Po¨lten, Austria Background: Talimogene Laherparepvec (TVEC), a genetically modified GM-CSF expressing HSV1 Virus that preferentially replicates in tumor cells is approved in Europe for use in melanoma patients with injectable metastatic lesions in stage IIIIVM1a. Approval was based on the OPTIM study which did also include patients with distant metastases and demonstrated a ORR of 40.5% and a CR rate of 16.6%. The aim of this study was to assess the outcome of melanoma patients treated with TVEC in a real life clinical setting outside of clinical studies. Methods: To this aim a retrospective chart review in 7 melanoma centers in Austria and 1 center in Switzerland was conducted and anonymized data on disease stage, treatment duration, treatment response by investigator assessment following RECIST 1.1, tolerability as well as data on follow up therapies was collected. Results: A total of 62 patients received TVEC since December of 2016. The majority of patients were AJCC stage IIIB and IIIC. Two patients with stage IV M1b and M1d who had complete control of their distant metastases and a locoregional progression were treated in parallel with a PD-1 antibody in one case and in parallel with a BRAF/MEK inhibitor combination in the other. In 3 other cases TVEC was used in combination with a PD-1 inhibitor as first-line of therapy. The median number of intralesional injection cycles was 11. The ORR was 67,7%; 50% of patients achieved a complete remission. 7 of 31 patients with a CR had a subsequent progression, 4 with distant and 3 with locoregional metastases. The main side effects observed were fever and chills. Conclusions: In this real life cohort treatment of TVEC shows a high overall and complete remission rate with the majority of complete responses being durable. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: C. Hoeller: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. J.M. Ressler: Speaker Bureau / Expert testimony: Amgen. H. Kehrer: Advisory / Consultancy: Amgen. P.
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in the head/neck, 15% on the trunk, and 11% upper limbs. At baseline, median age was 65 yrs, 94% had LDH ULN, 76% had ECOG PS 0 and 35% had nodular melanoma. T-VEC vs GM-CSF led to objective response rates of 56% vs 1%, CR rates of 24% vs 0%, and durable response rates of 34% vs 0% (all p < 0.002 vs GM-CSF). Median OS was not reached with T-VEC vs 25 months with GM-CSF (HR, 0.48; 95% CI, 0.28– 0.84; p ¼ 0.0088). The LR subpopulation experienced higher T-VEC efficacy vs the entire study population (Table). Conclusions: This analysis suggests that T-VEC may be of particular benefit in melanoma pts with LR recurrence, including ITM. Clinical trial identification: NCT00769704. Editorial acknowledgement: Ryan Woodrow, PhD, CMPP of Aspire Scientific (Bollington, UK), funded by Amgen (Europe) GmbH (Rotkreuz, Switzerland). Legal entity responsible for the study: Amgen Inc. Funding: Amgen Inc. Disclosure: M.R. Middleton: Advisory / Consultancy, Research grant / Funding (institution):
Annals of Oncology
abstracts
Annals of Oncology Koelblinger: Advisory / Consultancy: Amgen. F. Weihsengruber: Advisory / Consultancy: Amgen. J. Kofler: Advisory / Consultancy: Amgen. E. Richtig: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. O.A. Michielin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. C. Hafner: Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.
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Outcomes of advanced melanoma patients who discontinued pembrolizumab (pembro) after complete response (CR) in the French early access program (EAP)
Background: Information on outcomes after cessation of anti-PD-1 mAb for CR are scarce outside KN-001 & 006 trials. We investigated these outcomes in the French pembro EAP, where pts were less selected than in registration trials. Methods: A multicenter ambispective cohort of advanced melanoma pts initiating pembro between May 2014-Sept 2015 (CCTIRS, #15.640) was searched for pts who achieved CR. Overall and progression-free survivals with Log rank tests were used to compare curves. Results: 687 pts (159 with brain metastases) were included from 41 centers, which covered 75% of French pembro EAP. 79 pts (13%) achieved CR, among whom 68 (10%) stopped pembro for CR. Compared with the remaining 619 pts surveyed, these 68 pts had lower baseline serum LDH levels (54.5% vs 73.8%, respectively, were normal, p ¼ 0.016), lower ECOG PS (ECOG 0 for 298 (52.6%) and 54 (80.6%), respectively, p ¼ 0.001), and fewer metastatic sites (p ¼ 0.003). Of note, 10% of these 68 pts had >3 metastatic sites, 10% had brain metastases, 53% had 2010 AJCC stage M1c melanoma, and 67% had received previous treatment for advanced melanoma (mainly ipilimumab). Frequency of BRAFV600, NRAS, and c-kit mutation status was not different between pts who did or did not achieve CR. Median duration on pembro in these 68 pts was 21.2 m (range: 2.5-48.4, SD 10.0). Pembro was used alone to achieve CR in 79% of pts, while 4% received concurrent radiotherapy alone, 10% concurrent surgery alone, and 6% both treatments. At the cut-off date (13/09/2018), after a median follow-up since pembro initiation of 36.3 m and of 15.3 m since pembro cessation (2-31, SD 8.3), only 3% of pts experienced melanoma recurrence. Median recurrence-free survival was not achieved. These 2 pts received radiotherapy, with one partial response achieved. 5 pts died, with 2 deaths unrelated to melanoma (1 lymphoma, 1 chylothorax), 1 related to melanoma progression, and 2 of unknown causes. Conclusions: In this large real-life cohort, 10% of pts reached CR and discontinued pembro. All but 3% were recurrence-free after a median 15.3 m of treatment, thus validating the discontinuation of anti-PD1 in complete responders. Clinical trial identification: CCTIRS, #15.640. Editorial acknowledgement: RIC-Mel network and their team. Legal entity responsible for the study: MSD France. Funding: MSD France. Disclosure: P. Saiag: Honoraria (self), Advisory / Consultancy: MSD. L. Mortier: Honoraria (self), Advisory / Consultancy: MSD. C. Dutriaux: Honoraria (self), Advisory / Consultancy: MSD. L. Benmahammed: Full / Part-time employment: MSD. O. Morsli: Full / Part-time employment: MSD. C. Train: Full / Part-time employment: ClinSearch. A. Spampinato: Full / Part-time employment: MSD. M.T. Leccia: Honoraria (self), Advisory / Consultancy: MSD. N. Meyer: Advisory / Consultancy: MSD. J.J. Grob: Honoraria (self), Advisory / Consultancy: MSD.
Outcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI)
S. Knispel1, M. Gassenmaier2, A.M. Menzies3, C. Loquai4, D.B. Johnson5, C. Franklin6, R. Gutzmer7, J.C. Hassel8, C. Weishaupt9, T. Eigentler2, P. Schummer10, F. Kiecker11, C. Owen3, M.I. Schmidgen4, K.C. K€ahler12, C.G. Cann5, D. Niebel13, P. Mohr14, D. Schadendorf1, L. Zimmer1 1 Department of Dermatology, University Hospital of Essen, Essen, Germany, 2 Department of Dermatology, Center for Dermatooncology, University Medical Center Tu¨bingen, Tu¨bingen, Germany, 3Crown Princess Mary Cancer Centre Westmead, Melanoma Institute Australia, University of Sydney, Sydney, Australia, 4Department of Dermatology, Skin Cancer Center, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany, 5Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA, 6Department of Dermatology - Skin Cancer Center at the Center of Integrated Oncology (CIO), University Hospital Cologne, Cologne, Germany, 7Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany, 8Section of DermatoOncology, Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany, 9Department of Dermatology, University Hospital of Mu¨nster, Mu¨nster, Germany, 10Department of Dermatology, University Hospital Wu¨rzburg, Wu¨rzburg, Germany, 11Department of Dermatology, University Hospital Charite´ Berlin, Berlin, Germany, 12Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany, 13Department of Dermatology, University Hospital Bonn, Bonn, Germany, 14Department of Dermatology, Elbe-Klinikum Buxtehude, Buxtehude, Germany, Background: Elevated LDH is a known predictive and prognostic factor correlating with poor response rates and survival in patients (pts) with metastatic melanoma (MM) treated with targeted therapy (BRAF plus MEK inhibitors, TT) or immune checkpoint inhibitors (ICI). Whether TT or ICI in this subgroup of pts is more beneficial is unknown. Methods: Pts with MM and elevated LDH who started first-line therapy between March 2016 and June 2017 were retrospectively identified from 25 melanoma centers. The cohort was divided into 2 groups: pts receiving TT first-line (TT group) and ICI first-line (ICI group). Primary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Demographics and disease characteristics were also examined. Results: 404 pts with elevated LDH at start of first-line systemic treatment (ST) received either TT (n ¼ 90, 22%) or ICI (n ¼ 314, 78%). TT included dabrafenib and trametinib (73%) and vemurafenib and cobimetinib (27%). ICI included pembrolizumab (47%), nivolumab (11%) and combination ipilimumab and nivolumab (40%). Median (med) follow-up time was 11.2 months (mo). Med age was 65 years, 58% male, ECOG 1 46%, AJCC stage M1c 45%, M1d 31%, >3 organ sites 57%, BRAF-mutant 43%. 71% had LDH 1-2x upper limit normal (ULN), 27% >2x ULN. Age, sex, ECOG and AJCC stage were similar in both groups. All TT pts had BRAF mutant MM, compared to 32% with ICI. Pts in the TT group were more likely to have >3 organ sites involved (71% vs 54%, p ¼ 0.003) or LDH >2x ULN (34% vs 24%, p ¼ 0.15) compared to ICI group. The TT group had superior ORR (63% vs 36%, p 0.001) and PFS (med 4.7 mo vs 2.3 mo, p < 0.001), with similar OS (med 10.9 mo vs 17.9 mo, p ¼ 0.7) than the ICI group. 56% of the pts in the TT group and 39% of the pts in the ICI group received a subsequent ST. ORR, PFS and OS for the BRAF-mutant subgroup comparing first-line ICI vs. TT will be presented. Conclusions: In MM pts with elevated LDH at start of first-line ST, TT was associated with a higher ORR and longer med PFS. OS was similar in both groups, with patients undergoing ICI showing slightly longer med OS, however both groups did poorly. Clinical trials investigating the sequence of first-line therapies in pts with high medical need are urgently needed. Editorial acknowledgement: Kai-Martin Thoms, Go¨ttingen; Simone Goldinger, Zurich; Friedegund Meier, Dresden; Carola Berking, Munich; Raphael Reinhard, Mannheim; Laura Susok, Bochum; Paolo Ascierto, Naples; Konstantin Drexler, Regensburg; Claudia Pfo¨hler, Homburg; Julia Tietze, Augsburg; Alvaro Moreira, Erlangen. Legal entity responsible for the study: University Clinic Essen, Department of Dermatology. Funding: Has not received any funding. Disclosure: S. Knispel: Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Novartis. M. Gassenmaier: Advisory / Consultancy, Research grant / Funding (self): Novartis. A.M. Menzies: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. C. Loquai: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sun pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: Biontech; Advisory / Consultancy, Travel / Accommodation / Expenses: Almirall. D.B. Johnson: Advisory / Consultancy: Array Biopharma; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): BMS; Advisory / Consultancy, Licensing / Royalties: Genoptix; Advisory / Consultancy, Research grant / Funding (self): Incyte; Advisory / Consultancy: Merck; Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses: Genentech; Honoraria (institution): Pfizer; Honoraria (institution): Syndax; Honoraria (institution): Celldex; Honoraria (institution): Idera; Honoraria (institution): Merck; Honoraria (institution):
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P. Saiag1, L. Mortier2, C. Dutriaux3, L. Benmahammed4, O. Morsli4, C. Train5, A. Spampinato4, M.T. Leccia6, N. Meyer7, J.J. Grob8 1 Dermatology and Oncology, Universite´ de Versailles Saint Quentin en Yvelines, Boulogne, France, 2Dermatology and Oncology, Hopital Claude Huriez, Lille, France, 3 Dermatology and Paediatric Dermatology, CHU Bordeaux - Hopital St. Andre´, Bordeaux, France, 4Clinical Research, MSD France, Courbevoie, France, 5Clinical Research, ClinSearch, Malakoff, France, 6Dermatology and Oncology, CHU Albert Michalon, La Tronche, France, 7Medical Oncology-Skin, IUCT–Oncopole, Toulouse, France, 8Dermatology and Oncology, Hopital St. Marguerite Assistance Publique Hopitaux de Marseille, Marseille, France
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Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution): Immunocore; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Millennium; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Physiomics; Advisory / Consultancy, Research grant / Funding (institution): Rigontec; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Vertex; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Advisory / Consultancy, Research grant / Funding (institution): Immunocore; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Millennium; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Physiomics; Advisory / Consultancy, Research grant / Funding (institution): Rigontec; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Vertex. K. Harrington: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD. M. Ross: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck ; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen. K. Ohrling: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. H. Radcliffe: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. F. Collichio: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck.
v548 | Melanoma and other skin tumours
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Real life use of talimogene laherparepvec in melanoma in centers in Austria and Switzerland
C. Hoeller1, J.M. Ressler1, M. Karasek2, V. Aedo Lopez3, L. Koch4, H. Kehrer5, P. Koelblinger6, F. Weihsengruber7, J. Kofler8, E. Richtig9, O.A. Michielin10, C. Hafner11 1 Department of Dermatology, Medizinische Universitaet Wien (Medical University of Vienna), Vienna, Austria, 2Department of Dermatology, University Hospital St. Poelten, St. Poelten, Austria, 3Service d’Oncologie, CHUV - Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 4Department of Dermatology, Medical University of Graz, Graz, Austria,5Department of Dermatology, Krankenhaus der Elisabethinen, Linz, Austria, 6Department of Dermatology, Paracelsus Medical University, Salzburg, Austria, 7 Department of Dermatology and Venerology, Krankenanstalt Rudolfstiftung, Vienna, Austria, 8Department of Dermatology, Landeskrankenhaus LKH Klagenfurt am Woerthersee, Klagenfurt, Austria, 9Department of Dermatology, Institute of Pathology, Medical University of Graz, Graz, Austria, 10Oncology, Centre Hospitalier Universitaire Vaudois - CHUV, Lausanne, Switzerland, 11Department of Dermatology, University Hospital St. Po¨lten, Karl Landsteiner University of Health Sciences, St Po¨lten, Austria Background: Talimogene Laherparepvec (TVEC), a genetically modified GM-CSF expressing HSV1 Virus that preferentially replicates in tumor cells is approved in Europe for use in melanoma patients with injectable metastatic lesions in stage IIIIVM1a. Approval was based on the OPTIM study which did also include patients with distant metastases and demonstrated a ORR of 40.5% and a CR rate of 16.6%. The aim of this study was to assess the outcome of melanoma patients treated with TVEC in a real life clinical setting outside of clinical studies. Methods: To this aim a retrospective chart review in 7 melanoma centers in Austria and 1 center in Switzerland was conducted and anonymized data on disease stage, treatment duration, treatment response by investigator assessment following RECIST 1.1, tolerability as well as data on follow up therapies was collected. Results: A total of 62 patients received TVEC since December of 2016. The majority of patients were AJCC stage IIIB and IIIC. Two patients with stage IV M1b and M1d who had complete control of their distant metastases and a locoregional progression were treated in parallel with a PD-1 antibody in one case and in parallel with a BRAF/MEK inhibitor combination in the other. In 3 other cases TVEC was used in combination with a PD-1 inhibitor as first-line of therapy. The median number of intralesional injection cycles was 11. The ORR was 67,7%; 50% of patients achieved a complete remission. 7 of 31 patients with a CR had a subsequent progression, 4 with distant and 3 with locoregional metastases. The main side effects observed were fever and chills. Conclusions: In this real life cohort treatment of TVEC shows a high overall and complete remission rate with the majority of complete responses being durable. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: C. Hoeller: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. J.M. Ressler: Speaker Bureau / Expert testimony: Amgen. H. Kehrer: Advisory / Consultancy: Amgen. P.
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in the head/neck, 15% on the trunk, and 11% upper limbs. At baseline, median age was 65 yrs, 94% had LDH ULN, 76% had ECOG PS 0 and 35% had nodular melanoma. T-VEC vs GM-CSF led to objective response rates of 56% vs 1%, CR rates of 24% vs 0%, and durable response rates of 34% vs 0% (all p < 0.002 vs GM-CSF). Median OS was not reached with T-VEC vs 25 months with GM-CSF (HR, 0.48; 95% CI, 0.28– 0.84; p ¼ 0.0088). The LR subpopulation experienced higher T-VEC efficacy vs the entire study population (Table). Conclusions: This analysis suggests that T-VEC may be of particular benefit in melanoma pts with LR recurrence, including ITM. Clinical trial identification: NCT00769704. Editorial acknowledgement: Ryan Woodrow, PhD, CMPP of Aspire Scientific (Bollington, UK), funded by Amgen (Europe) GmbH (Rotkreuz, Switzerland). Legal entity responsible for the study: Amgen Inc. Funding: Amgen Inc. Disclosure: M.R. Middleton: Advisory / Consultancy, Research grant / Funding (institution):
Annals of Oncology
abstracts
Annals of Oncology Koelblinger: Advisory / Consultancy: Amgen. F. Weihsengruber: Advisory / Consultancy: Amgen. J. Kofler: Advisory / Consultancy: Amgen. E. Richtig: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. O.A. Michielin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. C. Hafner: Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.
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Outcomes of advanced melanoma patients who discontinued pembrolizumab (pembro) after complete response (CR) in the French early access program (EAP)
Background: Information on outcomes after cessation of anti-PD-1 mAb for CR are scarce outside KN-001 & 006 trials. We investigated these outcomes in the French pembro EAP, where pts were less selected than in registration trials. Methods: A multicenter ambispective cohort of advanced melanoma pts initiating pembro between May 2014-Sept 2015 (CCTIRS, #15.640) was searched for pts who achieved CR. Overall and progression-free survivals with Log rank tests were used to compare curves. Results: 687 pts (159 with brain metastases) were included from 41 centers, which covered 75% of French pembro EAP. 79 pts (13%) achieved CR, among whom 68 (10%) stopped pembro for CR. Compared with the remaining 619 pts surveyed, these 68 pts had lower baseline serum LDH levels (54.5% vs 73.8%, respectively, were normal, p ¼ 0.016), lower ECOG PS (ECOG 0 for 298 (52.6%) and 54 (80.6%), respectively, p ¼ 0.001), and fewer metastatic sites (p ¼ 0.003). Of note, 10% of these 68 pts had >3 metastatic sites, 10% had brain metastases, 53% had 2010 AJCC stage M1c melanoma, and 67% had received previous treatment for advanced melanoma (mainly ipilimumab). Frequency of BRAFV600, NRAS, and c-kit mutation status was not different between pts who did or did not achieve CR. Median duration on pembro in these 68 pts was 21.2 m (range: 2.5-48.4, SD 10.0). Pembro was used alone to achieve CR in 79% of pts, while 4% received concurrent radiotherapy alone, 10% concurrent surgery alone, and 6% both treatments. At the cut-off date (13/09/2018), after a median follow-up since pembro initiation of 36.3 m and of 15.3 m since pembro cessation (2-31, SD 8.3), only 3% of pts experienced melanoma recurrence. Median recurrence-free survival was not achieved. These 2 pts received radiotherapy, with one partial response achieved. 5 pts died, with 2 deaths unrelated to melanoma (1 lymphoma, 1 chylothorax), 1 related to melanoma progression, and 2 of unknown causes. Conclusions: In this large real-life cohort, 10% of pts reached CR and discontinued pembro. All but 3% were recurrence-free after a median 15.3 m of treatment, thus validating the discontinuation of anti-PD1 in complete responders. Clinical trial identification: CCTIRS, #15.640. Editorial acknowledgement: RIC-Mel network and their team. Legal entity responsible for the study: MSD France. Funding: MSD France. Disclosure: P. Saiag: Honoraria (self), Advisory / Consultancy: MSD. L. Mortier: Honoraria (self), Advisory / Consultancy: MSD. C. Dutriaux: Honoraria (self), Advisory / Consultancy: MSD. L. Benmahammed: Full / Part-time employment: MSD. O. Morsli: Full / Part-time employment: MSD. C. Train: Full / Part-time employment: ClinSearch. A. Spampinato: Full / Part-time employment: MSD. M.T. Leccia: Honoraria (self), Advisory / Consultancy: MSD. N. Meyer: Advisory / Consultancy: MSD. J.J. Grob: Honoraria (self), Advisory / Consultancy: MSD.
Outcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI)
S. Knispel1, M. Gassenmaier2, A.M. Menzies3, C. Loquai4, D.B. Johnson5, C. Franklin6, R. Gutzmer7, J.C. Hassel8, C. Weishaupt9, T. Eigentler2, P. Schummer10, F. Kiecker11, C. Owen3, M.I. Schmidgen4, K.C. K€ahler12, C.G. Cann5, D. Niebel13, P. Mohr14, D. Schadendorf1, L. Zimmer1 1 Department of Dermatology, University Hospital of Essen, Essen, Germany, 2 Department of Dermatology, Center for Dermatooncology, University Medical Center Tu¨bingen, Tu¨bingen, Germany, 3Crown Princess Mary Cancer Centre Westmead, Melanoma Institute Australia, University of Sydney, Sydney, Australia, 4Department of Dermatology, Skin Cancer Center, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany, 5Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA, 6Department of Dermatology - Skin Cancer Center at the Center of Integrated Oncology (CIO), University Hospital Cologne, Cologne, Germany, 7Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany, 8Section of DermatoOncology, Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany, 9Department of Dermatology, University Hospital of Mu¨nster, Mu¨nster, Germany, 10Department of Dermatology, University Hospital Wu¨rzburg, Wu¨rzburg, Germany, 11Department of Dermatology, University Hospital Charite´ Berlin, Berlin, Germany, 12Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany, 13Department of Dermatology, University Hospital Bonn, Bonn, Germany, 14Department of Dermatology, Elbe-Klinikum Buxtehude, Buxtehude, Germany, Background: Elevated LDH is a known predictive and prognostic factor correlating with poor response rates and survival in patients (pts) with metastatic melanoma (MM) treated with targeted therapy (BRAF plus MEK inhibitors, TT) or immune checkpoint inhibitors (ICI). Whether TT or ICI in this subgroup of pts is more beneficial is unknown. Methods: Pts with MM and elevated LDH who started first-line therapy between March 2016 and June 2017 were retrospectively identified from 25 melanoma centers. The cohort was divided into 2 groups: pts receiving TT first-line (TT group) and ICI first-line (ICI group). Primary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Demographics and disease characteristics were also examined. Results: 404 pts with elevated LDH at start of first-line systemic treatment (ST) received either TT (n ¼ 90, 22%) or ICI (n ¼ 314, 78%). TT included dabrafenib and trametinib (73%) and vemurafenib and cobimetinib (27%). ICI included pembrolizumab (47%), nivolumab (11%) and combination ipilimumab and nivolumab (40%). Median (med) follow-up time was 11.2 months (mo). Med age was 65 years, 58% male, ECOG 1 46%, AJCC stage M1c 45%, M1d 31%, >3 organ sites 57%, BRAF-mutant 43%. 71% had LDH 1-2x upper limit normal (ULN), 27% >2x ULN. Age, sex, ECOG and AJCC stage were similar in both groups. All TT pts had BRAF mutant MM, compared to 32% with ICI. Pts in the TT group were more likely to have >3 organ sites involved (71% vs 54%, p ¼ 0.003) or LDH >2x ULN (34% vs 24%, p ¼ 0.15) compared to ICI group. The TT group had superior ORR (63% vs 36%, p 0.001) and PFS (med 4.7 mo vs 2.3 mo, p < 0.001), with similar OS (med 10.9 mo vs 17.9 mo, p ¼ 0.7) than the ICI group. 56% of the pts in the TT group and 39% of the pts in the ICI group received a subsequent ST. ORR, PFS and OS for the BRAF-mutant subgroup comparing first-line ICI vs. TT will be presented. Conclusions: In MM pts with elevated LDH at start of first-line ST, TT was associated with a higher ORR and longer med PFS. OS was similar in both groups, with patients undergoing ICI showing slightly longer med OS, however both groups did poorly. Clinical trials investigating the sequence of first-line therapies in pts with high medical need are urgently needed. Editorial acknowledgement: Kai-Martin Thoms, Go¨ttingen; Simone Goldinger, Zurich; Friedegund Meier, Dresden; Carola Berking, Munich; Raphael Reinhard, Mannheim; Laura Susok, Bochum; Paolo Ascierto, Naples; Konstantin Drexler, Regensburg; Claudia Pfo¨hler, Homburg; Julia Tietze, Augsburg; Alvaro Moreira, Erlangen. Legal entity responsible for the study: University Clinic Essen, Department of Dermatology. Funding: Has not received any funding. Disclosure: S. Knispel: Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Novartis. M. Gassenmaier: Advisory / Consultancy, Research grant / Funding (self): Novartis. A.M. Menzies: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. C. Loquai: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sun pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: Biontech; Advisory / Consultancy, Travel / Accommodation / Expenses: Almirall. D.B. Johnson: Advisory / Consultancy: Array Biopharma; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): BMS; Advisory / Consultancy, Licensing / Royalties: Genoptix; Advisory / Consultancy, Research grant / Funding (self): Incyte; Advisory / Consultancy: Merck; Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses: Genentech; Honoraria (institution): Pfizer; Honoraria (institution): Syndax; Honoraria (institution): Celldex; Honoraria (institution): Idera; Honoraria (institution): Merck; Honoraria (institution):
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz255 | v549
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P. Saiag1, L. Mortier2, C. Dutriaux3, L. Benmahammed4, O. Morsli4, C. Train5, A. Spampinato4, M.T. Leccia6, N. Meyer7, J.J. Grob8 1 Dermatology and Oncology, Universite´ de Versailles Saint Quentin en Yvelines, Boulogne, France, 2Dermatology and Oncology, Hopital Claude Huriez, Lille, France, 3 Dermatology and Paediatric Dermatology, CHU Bordeaux - Hopital St. Andre´, Bordeaux, France, 4Clinical Research, MSD France, Courbevoie, France, 5Clinical Research, ClinSearch, Malakoff, France, 6Dermatology and Oncology, CHU Albert Michalon, La Tronche, France, 7Medical Oncology-Skin, IUCT–Oncopole, Toulouse, France, 8Dermatology and Oncology, Hopital St. Marguerite Assistance Publique Hopitaux de Marseille, Marseille, France
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