Preliminary results from the international neoadjuvant melanoma consortium (INMC).

9581 Background: For several cancers, response to neoadjuvant therapy (NAT) correlates with survival. Targeted and immune therapies achieve high response rates and durable survival in many patients with metastatic melanoma. Their role as NAT for stage III disease is not clear, and whether pathological response following NAT correlates with relapse-free (RFS) or overall survival (OS) in melanoma is unknown. Methods: Pooled clinical data from four ongoing NAT clinical trials (NCT02437279, NCT02231775, NCT02519322, NCT01972347) at three large melanoma centers participating in the INMC were examined. All trials included only patients with surgically resectable clinical stage III melanoma. NAT regimens included dabrafenib/trametinib (DT) and nivolumab (nivo) [single agent or in combination with ipilimumab (ipi/nivo)]. Patients who had undergone surgery prior to 27th January 2017 are included in this preliminary analysis. A pathological complete response (pCR) was defined as no viable melanoma cells in the resected specimen by hematoxylin and eosin evaluations by dedicated dermatopathologists. Results: 58 patients with clinical stage III melanoma (AJCCv7: 18 IIIB, 40 IIIC) have completed NAT and undergone surgery. 18 received neoadjuvant immunotherapy (IT): ipi/nivo x2 doses (N = 10), ipi/nivo x3 doses (N = 4) or nivo x4 doses (N = 4). 40 received neoadjuvant DT, either for two (N = 10) or three months (N = 30). Median age is 55 years (range 22-84). A pCR was observed in 50% of patients, 7 (39%) with IT and 22 (55%) with DT. Median follow-up is 10.2 months (95% CI 8.7-12.5). 14 (24%) patients have recurred (5 local, 8 distant, 1 both), 2 (11%) after IT, 12 (30%) after DT. For those with pCR, 14% have recurred, 0/7 (0%) after IT, 4/22 (18%) after DT. In contrast, for those without pCR, 34% have recurred, 2/11 (18%) after IT and 8/18 (44%) after DT. Two deaths have occurred, both after neoadjuvant TT. Early data suggests improved RFS in those with pCR. Conclusions: Neoadjuvant targeted and immunotherapy are active regimens in clinical stage III melanoma patients and are associated with high pCR rate. Preliminary data suggest pCR correlates with improved RFS. Updated data will be presented. Clinical trial information: NCT02437279, NCT02231775, NCT02519322, NCT01972347.

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Pathological response and survival with neoadjuvant therapy in melanoma: A pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.9503 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 9503-9503 ◽

Cited By ~ 18

Author(s):

Alexander M. Menzies ◽

Elisa A. Rozeman ◽

Rodabe Navroze Amaria ◽

Alexander Chan Chi Huang ◽

Richard A. Scolyer ◽

...

Keyword(s):

Targeted Therapy ◽

Clinical Stage ◽

Complete Response ◽

Pooled Analysis ◽

Stage Iii ◽

Post Surgery ◽

Neoadjuvant Immunotherapy ◽

Neoadjuvant Systemic Therapy ◽

Melanoma Patients ◽

Stage Iii Melanoma

9503 Background: Pathological complete response (pCR) to neoadjuvant systemic therapy (NST) correlates with survival, and is recognized as a path to regulatory approval in several cancers. Recent trials have reported that neoadjuvant immunotherapy (IT) and targeted therapy (TT) regimens achieve high pCR rates and impressive recurrence-free survival in stage III melanoma, however, the relationship between pCR, relapse-free (RFS) and overall survival (OS) in larger datasets of melanoma patients (pts) remains unknown. Methods: We pooled data from 6 modern NST clinical trials of anti-PD-1 based immunotherapy or BRAF/MEK targeted therapy conducted across institutions participating in the INMC. Pts with RECIST measurable, surgically resectable clinical stage III melanoma who underwent surgery were included. NST regimens included nivolumab (as monotherapy or in combination with ipilimumab), pembrolizumab or dabrafenib+trametinib. Baseline disease characteristics, treatment regimen, pCR and RFS were examined. Results: 184 pts with clinical stage III melanoma (AJCCv7: 100 IIIB, 84 IIIC) completed NST (133 IT, 51 TT) and underwent surgery. Median age was 57y (range 18-87). A pCR was observed in 41% of patients; 51 (38%) with IT and 24 (47%) with TT. Median follow-up post-surgery is 13 mo (95% CI 12-16); 10 mo with IT and 22 mo with TT. 44 (24%) pts have recurred (17 loco-regional, 21 distant, 6 both sites at first recurrence), 18 (14%) after IT and 26 (51%) after TT. 12-month RFS was improved with IT vs TT (83% vs 65%, p < 0.001). For those with pCR, 7% have recurred, 0/51 (0%) after IT, 7/17 (41%) after TT. For those without pCR, 34% have recurred, 18/82 (22%) after IT and 19/27 (70%) after TT. 12-month RFS was improved in those with pCR vs without pCR (95% vs 62%, p < 0.001), including in those with IT (100% vs 72%, p < 0.001) and TT (88% vs 43%, p < 0.001). 16 (9%) patients have died including two who had a pCR, both from TT. Conclusions: Neoadjuvant IT and TT are active regimens in resectable clinical stage III melanoma patients and are associated with high pCR rate. The ability to achieve pCR correlates with improved RFS and remarkably no patient with pCR from immunotherapy has recurred to date.

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FDG-PET/CT response and outcome of neoadjuvant immunotherapy for clinical stage III melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21569 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21569-e21569

Author(s):

Milton Jose De Barros E. Silva ◽

Caio Dabbous Liz ◽

Marcos Rezende Teixeira ◽

José Augusto Rinck ◽

Monique Celeste Tavares ◽

...

Keyword(s):

Fdg Pet ◽

Clinical Stage ◽

Complete Response ◽

The Other ◽

Stage Iii ◽

Mixed Response ◽

Neoadjuvant Immunotherapy ◽

Pet Ct ◽

Stage Iii Melanoma ◽

Fdg Pet Ct

e21569 Background: Neoadjuvant immunotherapy with nivolumab 3mg/kg and ipilimumab 1mg/kg for two cycles(N3+I1) or anti-PD1 for 3-8 weeks for clinical stage III melanoma have shown rates of pCR/near-pCR about 60% or 30%, respectively. The prognosis of this group seems to be excellent so far. On the other hand, patients classified as pathological non-response have a worse outcome and early identification of this group may allow us to tailor treatment before surgery. Methods: We conducted a retrospective analysis of patients with clinical stage III melanoma treated with neoadjuvant immune checkpoint blockade who did baseline and pre-operative FDG-PET/CT. The total number of FGD avid lesions and the percentual difference between the maximum SUV per lesion was calculated. The pathological results were correlated to FGD-PET/CT findings. Results: Between January 2019 and January 2021, nine patients with clinical stage III melanoma were identified. Six patients received Nivolumab 3m/kg and Ipilimumab 1mg/kg for two cycles and 3 received anti-PD1 for 60 days. Baseline FDG-PET/CT showed just one avid lesion in 7 patients, 2 avid lesions in one patient and 3 avid lesions in one patient. All known lesions identified by CT scan were also captured by FGD-PET/CT. After the neoadjuvant treatment, 4 patients achieved pCR/near-pCR. All of them were treated with N3+I1. Two of them had metabolic complete response (including the one with 3 PET- avid lesions) and 2 had reduction on FDG concentration (-31% and – 76%). Three patients had absence of response: 100% of viable tumor cells (VTC), all of them with increase in FDG concentration (+12% to + 307%) and appearance of a new lesion in one case. Two out of them were treated with anti-PD1. One patient had partial response (40% of VTC). Interestingly, this patient developed sarcoidosis-like reaction with increase of SUV in the index lesion (+68%) and appearance of mediastinal lymph-nodes. One patient, who had two lesions, presented a mixed response: complete response in one and 90% of VTC in the other. FDG-PET/CT was able to detect both responses (metabolic complete response and increase of FGD concentration of 17%, respectively). Conclusions: Reduction in FGD-PET/CT concentration with no appearance of new lesion(s) is associated with significant pathological response. An increase of SUV or appearance of new lesion(s) should be carefully interpreted.

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Concomitant antibiotics (ATBs) use and survival outcomes in patients (pts) with muscle-invasive bladder cancer (MIBC) treated with neoadjuvant pembrolizumab (PURE-01 study).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.449 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 449-449

Author(s):

Daniele Raggi ◽

Marco Bandini ◽

Filippo Pederzoli ◽

Patrizia Giannatempo ◽

Laura Marandino ◽

...

Keyword(s):

Cox Regression ◽

Negative Impact ◽

Clinical Stage ◽

Single Agent ◽

Pathologic Complete Response ◽

Complete Response ◽

Disease Stage ◽

Study Cohort ◽

Chi Square ◽

Neoadjuvant Immunotherapy

449 Background: Administration of single-agent neoadjuvant immunotherapy (IO) proved to be effective and safe in the treatment of MIBC, and the identification of reliable predictors of treatment-failure would allow a more precise implementation in clinical practice. In advanced/metastatic urothelial carcinoma, ATB therapy has a negative impact on IO efficacy by modulating the intestinal microbiota towards a detrimental state of dysbiosis, eventually impairing the host anticancer immunity. However, evidences of such an effect in more confined disease, managed with an intention-to-cure attitude, are still lacking. Methods: A post hoc analysis was conducted in pts prospectively enrolled in PURE-01 study (NCT02736266), in which MIBC patients received 3 cycles of neoadjuvant pembrolizumab. ATB use was defined as any ATB administration between 30 days prior to the first pembrolizumab dose and the planned RC. Kruskal-Wallis and Chi-square tests for differences between patients treated or not with ATBs according to baseline characteristics were used. Endpoints of the study were pathologic complete response (ypT0N0) and 12- and 24-mo relapse-free survival (RFS). Multivariable logistic regression (MLR) tested the effect of ATB use on ypT0N0 rate. Secondary, we assessed RFS according to ATB use using Kaplan-Meier and multivariable Cox regression (MCR). Analyses were adjusted for baseline T stage of disease (stage II vs III), PD-L1 expression (CPS >10% vs <10%) and tumor mutational burden (TMB). Sub-analyses explored the effect of different ATB classes on the aforementioned outcomes. Results: The study cohort included 149 pts treated with neoadjuvant pembrolizumab, of which 140 (94%) underwent RC. Of all individuals, 48 pts (32%) received concomitant ATB treatment. Median TMB (9.3 Mut/Mb vs 11.4 Mut/Mb, p=0.005) and CPS (9.5% vs. 20%, p=0.04) were lower in the subgroup of patients treated with ATBs. At MLR analysis, ATB use was associated with significantly lower rate of ypT0N0 (OR 0.18, [95%CI] = 0.05-0.48, p=0.001). Patients receiving ATBs exhibited shorter 12-mo (80% [70-93] vs. 95% [91-99]) and 24-mo (63% [48-83] vs. 90% [83-97]) RFS rates than pts non receiving ATB. MCR analyses assessed that ATB treatment conferred higher risk of recurrence (HR =2.64 [1.08-6.50], p=0.03) compared to no ATB treatment, after adjusting for CPS, TMB and clinical stage at diagnosis. Fluoroquinolones were significantly associated with the worst outcomes (12-mo RFS 74% (55-99); 24-mo RFS: 61% (40-91); p=0.011; adjusted HR = 3.28 [1.12-9.60], p=0.03). Conclusions: ATB treatment was demonstrated as independently associated with lower rate of ypT0N0 and shorter RFS in MIBC treated with neoadjuvant pembrolizumab. More robust data testing the interactions between immunotherapy and gut and urinary microbiota are urgently needed. Clinical trial information: NCT02736266.

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Efficacy of adjuvant radiotherapy in recurrent melanoma after adjuvant immunotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9578 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9578-9578

Author(s):

Prachi Bhave ◽

Angela M. Hong ◽

Rebecca Johnson ◽

Alexander M. Menzies ◽

Georgina V. Long ◽

...

Keyword(s):

High Risk ◽

Selection Bias ◽

Single Agent ◽

Stage Iii ◽

Prospective Data ◽

Disease Characteristics ◽

Stage Iii Melanoma ◽

Resected Stage ◽

In Transit

9578 Background: Adjuvant (adj) radiotherapy (RT) halves the risk of locoregional (LR) recurrence in patients (pts) with high risk stage III melanoma after lymphadenectomy (CLND), however its role in the adj immunotherapy (IO) era without CLND is unknown. Methods: Pts with resected stage III melanoma who received adj IO and recurred with resectable LR only disease were studied. After resection of this 1st recurrence, adj RT may or may not have been administered. Disease characteristics, treatment at relapse and outcomes were examined. Results: 71 pts from 9 centres were included. Prior to adj IO, median age was 60y, 59% male, 56% BRAF mutant, 61% stage IIIC (AJCC V8), 52% underwent CLND and 17% had in-transit (IT) only disease. Adj IO included: 90% single agent anti-PD1, 8% ipilimumab-nivolumab (IN) and 1% nivolumab or IN (blinded on trial). Median duration of adj IO was 5 months. 21(30%) pts had high risk stage III disease at diagnosis, per previously established TROG criteria; 3 (4%) received upfront adj RT prior to recurrence. Median time to 1st recurrence was 7 months. 49 (69%) pts recurred during and 22 (31%) after cessation of adj IO. At 1st recurrence, 9 (13%) pts had stage IIIB disease, 55 (77%) IIIC, 7 (10%) IIID and 8 (11%) continued prior adj IO, 31 (44%) commenced therapy and 32 (45%) had no systemic therapy. 24 (34%) pts received adj RT after resection of 1st recurrence and 47 (66%) did not (Table). Adj RT was associated with a reduced risk of any 2nd recurrence (7/24, 29% vs 26/47, 55%, p=0.03) and LR 2nd recurrence (2/24, 8% vs 17/47, 36%, p=0.012). Whilst pts who received adj RT at 1st recurrence were more likely to have LN only disease, extra nodal extension and involved surgical margins, these factors did not significantly affect overall risk of 2nd recurrence on multivariate analysis. Of note, 70% of pts who did not receive adj RT at 1st recurrence had IT only disease, and though this did not significantly affect rate of 2nd recurrence (p=0.19), this likely reflects an inherent selection bias in this study. RT toxicity occurred in 16 (67%) pts, 10 with dermatitis only, and all grade 1 or 2. Median follow up was 22 months. Median recurrence free survival to 2nd recurrence was 23 months for all pts, not reached for those who had adj RT at 1st recurrence and 19 months for those who did not have adj RT (p=0.047). Median overall survival was not reached. Conclusions: Whilst adj RT appears to reduce 2nd recurrences, this may have been influenced by an unavoidable selection bias in the data, particularly an imbalance in the percentage of pts with IT disease. Prospective data with larger cohorts is needed to validate our results.[Table: see text]

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Utility of concomitant chemoradiotherapy with 5-fluorouracil (5-FU) single agent as neoadjuvant treatment regimen in mexican patients with stage III rectal cancer: Experience in the Oncology Hospital

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15144 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15144-e15144

Author(s):

J. Gomez Rangel ◽

O. Alvarez Ordorica ◽

R. Villalobos Valencia ◽

J. A. Silva

Keyword(s):

Overall Survival ◽

Clinical Stage ◽

Single Agent ◽

Neoadjuvant Treatment ◽

Disease Free Survival ◽

Conservative Surgery ◽

Stage Iii ◽

Grade 3 ◽

Cancer Experience

e15144 Background: To analyze overall survival, free disease survival, complete and partial pathologic response, effect of stage reduction, toxicity profile and number of anus preservative surgery in patients treated with concurrent chemo radiotherapy with a modified 5-FU single agent regimen as neoadjuvant modality treatment. Methods: Historic Cohort of patients treated in the Oncology Hospital, CMNSXXI between January 1999 to December 2004. The scheme used was a bolus of 5FU 425mg/m2 without leocovorin in three consecutive days each two weeks (days 1–3, 15 -17 and 29–31). Results and Conclusions: There were identified 96 consecutive patients with clinical stage III. The median age was 57.5 years. Ninety and two patients were operated and 51% was candidates to conservative surgery. There were 12.5% of complete pathologic responses and 35% of partial responses. The median of survival has not been reached. The five years of overall survival was 62% and the five-years of disease free survival was 55%. Stage reduction had impact in overall survival with 65% vs 40% at 9.5 years of follow up, and DFS was 58% vs 48% at 9.5 years. We report 16 cases of gastrointestinal toxicity grade 3 and two cases with grade 4. There was reported fourth cases of afebril neutropenia grade 4. Results in OS, DFS and number of complete pathological response were similar to reported by another oncology groups. Stage reduction was traduced in an increased of OS. This schedule can be feasible and applicable in another institutions in develop countries. No significant financial relationships to disclose.

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Immunopharmacologic Analysis of an Autologous, Hapten-Modified Human Melanoma Vaccine

Journal of Clinical Oncology ◽

10.1200/jco.2004.06.043 ◽

2004 ◽

Vol 22 (3) ◽

pp. 403-415 ◽

Cited By ~ 100

Author(s):

David Berd ◽

Takami Sato ◽

Henry C. Maguire ◽

John Kairys ◽

Michael J. Mastrangelo

Keyword(s):

Tumor Cells ◽

Cancer Vaccine ◽

Human Cancer ◽

Clinical Stage ◽

Melanoma Cells ◽

Stage Iii ◽

Delayed Type Hypersensitivity ◽

Autologous Tumor ◽

Stage Iii Melanoma

Purpose We have previously reported a clinical trial of a human cancer vaccine consisting of autologous tumor cells modified with the hapten, dinitrophenyl (DNP), in patients with clinical stage III melanoma. Here we present a follow-up report expanded to 214 patients with 5-year follow-up. Patients and Methods Two hundred fourteen patients with clinical stage III melanoma (117 patients with stage IIIC and 97 patients with stage IIIB) who were melanoma-free after standard lymphadenectomy were treated with multiple intradermal injections of autologous, DNP-modified vaccine mixed with bacille Calmette-Guérin. Four vaccine dosage schedules were tested sequentially, all of which included low-dose cyclophosphamide. Patients were tested for delayed-type hypersensitivity (DTH) to autologous melanoma cells, both DNP-modified and unmodified, and to control materials. Results The 5-year overall survival (OS) rate of the 214 patients was 44%. DTH responses to unmodified autologous melanoma were induced in 47% of patients. The OS of this DTH-positive group was double that of DTH-negative patients (59.3% v 29.3%; P < .001). In contrast, positive DTH responses to DNP-modified autologous melanoma cells and to purified protein derivative developed in almost all patients but did not affect OS. Surprisingly, the OS after relapse was also significantly longer in patients who developed positive DTH to unmodified tumor cells (25.2% v 12.3%; P < .001). Finally, the development of DTH was dependent on the schedule of administration of the vaccine, specifically, the timing of an induction dose administered at the beginning of the treatment program. Conclusion This study underscores the importance of the immunopharmacology of the autologous, DNP-modified vaccine and may be relevant to other cancer vaccine technologies.

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Bilateral facial neuritis associated with dabrafenib and trametinib after failure of neoadjuvant immunotherapy for stage III melanoma

ANZ Journal of Surgery ◽

10.1111/ans.16992 ◽

2021 ◽

Author(s):

Andrew T. Li ◽

Aung Min Maw ◽

Edward Hsiao ◽

Sydney Ch'ng ◽

Georgina V. Long ◽

...

Keyword(s):

Stage Iii ◽

Neoadjuvant Immunotherapy ◽

Stage Iii Melanoma

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Neoadjuvant and adjuvant nivolumab (nivo) with anti-LAG3 antibody relatlimab (rela) for patients (pts) with resectable clinical stage III melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9502 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9502-9502

Author(s):

Rodabe Navroze Amaria ◽

Michael A. Postow ◽

Michael T. Tetzlaff ◽

Merrick I. Ross ◽

Isabella Claudia Glitza ◽

...

Keyword(s):

Adjuvant Treatment ◽

Clinical Stage ◽

Pathologic Response ◽

Stage Iii ◽

Toxicity Profile ◽

Radiographic Response ◽

Recist 1.1 ◽

Viable Tumor ◽

Stage Iii Melanoma ◽

Favorable Toxicity Profile

9502 Background: Neoadjuvant therapy (NT) for pts with clinical stage III melanoma remains an active area of research interest. Recent NT trial data demonstrates that achieving a pathologic complete response (pCR) correlates with improved relapse-free (RFS) and overall survival (OS). Checkpoint inhibitor (CPI) NT with either high or low dose ipilimumab and nivolumab regimens produces a high pCR rate of 30-45% but with grade 3-4 toxicity rate of 20-90%. In metastatic melanoma (MM), the combination of nivo with rela (anti Lymphocyte Activation Gene-3 antibody) has demonstrated a favorable toxicity profile and responses in both CPI-naïve and refractory MM. We hypothesized that NT with nivo + rela will safely achieve high pCR rates and provide insights into mechanisms of response and resistance to this regimen. Methods: We conducted a multi-institutional, investigator-initiated single arm study (NCT02519322) enrolling pts with clinical stage III or oligometastatic stage IV melanoma with RECIST 1.1 measurable, surgically-resectable disease. Pts were enrolled at 2 sites and received nivo 480mg IV with rela 160mg IV on wks 1 and 5. Radiographic response (RECIST 1.1) was assessed after completion of NT; surgery was conducted at wk 9 and specimens were assessed for pathologic response per established criteria. Pts received up to 10 additional doses of nivo and rela after surgery, with scans every 3 mo to assess for recurrence. The primary study objective was determination of pCR rate. Secondary objectives included safety, radiographic response by RECIST 1.1, event-free survival (EFS), RFS, and OS analyses. Blood and tissue were collected at baseline, at day 15, day 28, and at surgery for correlative analyses. Results: A total of 30 pts (19 males, median age 60) were enrolled with clinical stage IIIB/IIIC/IIID/IV (M1a) in 18/8/2/2 pts, respectively. 29 pts underwent surgery; 1 pt developed distant metastatic disease while on NT. pCR rate was 59% and near pCR ( < 10% viable tumor) was 7% for a major pathologic response (MPR, pCR + near pCR) of 66%. 7% of pts achieved a pPR (10-50% viable tumor) and 27% pNR (≥50% viable tumor). RECIST ORR was 57%. With a median follow up of 16.2 mos, the 1 -year EFS was 90%, RFS was 93%, and OS was 95%. 1-year RFS for MPR was 100% compared to 80% for non-MPR pts (p = 0.016). There were no treatment related gr 3/4 AEs that arose during NT; 26% of pts had a gr 3/4 AE that began during adjuvant treatment. Conclusions: Neoadjuvant and adjuvant treatment with nivo and rela achieved high pCR and MPR rates with a favorable toxicity profile in the neoadjuvant and adjuvant settings. Pts with MPR had improved outcomes compared to non-MPR pts. Translational studies to discern mechanisms of response and resistance to this combination are underway. Clinical trial information: NCT02519322.

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Outcomes of BRAF mutant metastatic melanoma (MM) patients (pts) after cessation of targeted therapy (TT) with BRAF or BRAF/MEK inhibitor(i).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9564 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9564-9564

Author(s):

Natalie Jackson ◽

Theresa Rodgers ◽

Ida John ◽

Denai R. Milton ◽

Lauren Elaine Haydu ◽

...

Keyword(s):

Single Agent ◽

Complete Response ◽

Braf V600e ◽

Response To Treatment ◽

Cancer Center ◽

Full Cohort ◽

Time To Recurrence ◽

Braf Mutant ◽

Unacceptable Toxicity

9564 Background: Since their introduction into the clinic a decade ago, BRAF and BRAF/MEKi have dramatically changed the outcomes of pts with BRAF mutant MM. While typically, these agents are administered until progression (PD), other reasons for stopping TT include unacceptable toxicity, complete response to treatment, or pt/physician decision or preference. The outcomes for MM pts that stop TT for reasons other than PD are largely unknown. Here we report the clinical features and outcomes of the largest cohort of MM pts who stopped TT for reasons other than PD to date. Methods: Under an institutionally approved database, we identified MM pts treated at the MD Anderson Cancer Center with BRAF±MEK inhibitors, and their records were reviewed to identify pts that stopped TT for reasons other than PD. Pts demographics, treatment information and clinical outcomes were recorded. Overall survival (OS) time was computed from three start dates (initial diagnosis, initial unresectable stage III melanoma, 1st dose of TT) to last known vital sign. Pts alive at the last follow-up date were censored. Time to recurrence was computed from date of 1st dose of TT to recurrence. Pts who did not experience disease recurrence were censored The Kaplan-Meier method was used to estimate OS and time to recurrence. Results: A total of 58 pts were identified, 32 (55%) were male. Most pts had a BRAF V600E (n = 49) or V600K (n = 6) mutation. At TT initiation median age was 59.5 years (range 29- 95), LDH was within normal range in 46 (85%), median number of prior systemic therapies was 1 (range 0-5), with 50% of pts receiving prior systemic therapy. Most (n = 33; 57%) pts were treated with single agent BRAFi (12 with dabrafenib, 11 vemurafenib). Among pts treated with combination TT (n = 25), most received dabrafenib with trametinib (n = 21; 84%). Median TT treatment duration was 9.5 months (range 0.03-80.5 months). Reasons for TT discontinuation were unacceptable toxicity (n = 29; 50%) and pt or physician decision/preference in responding patients (n = 23; 40%). At time of TT discontinuation, 48% of pts had achieved a complete response (CR), 28% a partial response (PR), and 22% stable disease (SD), 1 patient had unknown disease status. With standard follow-up, after stopping TT, 40 pts (69%) have recurred or experienced PD, with a median time to recurrence of 14.9 months (95% CI:7.8-26.3 months). At PD, 32 (76%) of pts had new metastatic sites. After PD 26 pts (63%) pts received BRAF/MEKi, 11 (44%) achieved a CR and 6 (24%) a PR, and 5 (20%) for a response rate of 88%; while 3 (12%) pt had PD as best response and 1 was unknown. For the full cohort, the median OS from time of 1st dose of TT was 6.4 years. Conclusions: Among MM pts who stopped TT for reasons other than PD, the majority of pts recurred, but most responded to re-introduction of TT. This information can help to inform discussion with pts regarding cessation of, or re-challenge with, TT.

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