CMET-36. IMMUNOTHERAPY VERSUS STANDARD OF CARE IN MELANOMA BRAIN METASTASES WITH KNOWN BRAF STATUS

Abstract INTRO/OBJECTIVE A mutation of the BRAF protein is seen in approximately 50% of melanoma patients. Immune checkpoint inhibitors (ICI) are standard therapy in melanoma patients independent of a patient’s BRAF status. The primary objective of this study is to investigate the impact of BRAF status in patients treated with ICI compared to non-ICI systemic therapy on overall survival (OS) in patients with melanoma brain metastasis (MBM). METHODS We reviewed 351 patients with MBM treated at our tertiary care center between 2000 and 2018. Of these, 144 had known BRAF status, 71 of which were BRAF mutant and 73 were BRAF wild-type. OS was calculated from the date of diagnosis of MBM to compare the efficacy of ICI to other systemic therapies. Many of these patients received multiple lines of treatment including targeted therapies at some point during their care. The log-rank test and Cox proportional hazard model was utilized to determine differences in OS. RESULTS Eighty-four percent of patients received local therapy that included either surgery, stereotactic radiosurgery, or whole brain radiation therapy. In BRAF wild-type patients, 40 received ICI and 33 underwent non-ICI systemic therapy with a median survival (5.6 vs 7.1 months) and 2-year survival (28% vs 32%), respectively (p=0.64). Of the BRAF mutant patients, 33 received ICI and 38 did not with a median survival (17.1 vs 9.0 months) and 2-year survival (36% and 19%), respectively (p=0.014). When controlling for age, KPS, ECM, and number of lesions, BRAF mutant MBM patients treated with ICI compared to non-ICI had an OS hazard ratio, HR=0.4 (95% CI=0.21 – 0.78, p=0.0069). CONCLUSION ICI therapy in BRAF mutant MBM patients results in improved OS compared to those with non-ICI systemic therapy. No such difference was observed in the BRAF wild-type cohort.

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THER-13. IMMUNOTHERAPY VERSUS STANDARD OF CARE IN MELANOMA BRAIN METASTASES WITH KNOWN BRAF STATUS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.056 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i13-i13

Author(s):

Addison Barnett ◽

Soumya Sagar ◽

Adam Lauko ◽

Wei Wei ◽

Samuel Chao ◽

...

Keyword(s):

Brain Metastasis ◽

Median Survival ◽

Systemic Therapy ◽

Tertiary Care ◽

Local Therapy ◽

Rank Test ◽

Wild Type ◽

Melanoma Patients ◽

The Impact ◽

Braf Mutant

Abstract BACKGROUND: A mutation of the BRAF protein is seen in approximately 50% of melanoma patients. Immune checkpoint inhibitors (ICI) are standard therapy in melanoma patients independent of a patient’s BRAF status. The primary objective of this study is to investigate the impact of BRAF status in patients treated with ICI compared to non-ICI systemic therapy on overall survival (OS) in patients with melanoma brain metastasis (MBM). METHODS: We reviewed 351 patients with MBM treated at our tertiary care center between 2000 and 2018. Of these, 144 had known BRAF status, 71 of which were BRAF mutant and 73 were BRAF wild-type. OS was calculated from the date of diagnosis of brain metastasis to compare the efficacy of ICI to other systemic therapies. Many of these patients received multiple lines of treatment including targeted therapies at some point during their care. The log-rank test and Cox proportional hazard model was utilized to determine differences in OS. RESULTS: Eighty-four percent of patients received local therapy that included either surgery, stereotactic radiosurgery or whole brain radiation therapy. In BRAF wild-type patients, 40 received ICI and 33 underwent non-ICI systemic therapy with a median survival (5.6 vs 7.1 months) and 2-year survival (28% vs 32%), respectively (p=0.64). Of the BRAF mutant patients, 33 received ICI and 38 did not with a median survival (17.1 vs 9.0 months) and 2-year survival (36% and 19%), respectively (p=0.014). When controlling for age, KPS, ECM, and number of lesions, BRAF mutant MBM patients treated with ICI compared to non-ICI had an OS hazard ratio, HR=0.4 (95% CI=0.21 – 0.78, p=0.0069). CONCLUSIONS: ICI therapy in BRAF mutant MBM patients results in improved OS compared to those with non-ICI systemic therapy. No such difference was observed in the BRAF wild-type cohort.

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THER-10. IMPACT OF BRAF MUTATIONAL STATUS ON THE EFFICACY OF IMMUNOTHERAPY FOR MELANOMA BRAIN METASTASES

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.053 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i12-i13

Author(s):

Adam Lauko ◽

Soumya Sagar ◽

Addison Barnett ◽

Wei Wei ◽

Samuel Chao ◽

...

Keyword(s):

Brain Metastases ◽

Tertiary Care ◽

Rank Test ◽

P Value ◽

Wild Type ◽

Braf Mutations ◽

Mutational Status ◽

Melanoma Brain Metastases ◽

Melanoma Patients ◽

Braf Mutant

Abstract BACKGROUND: BRAF mutations occur in 50% of melanoma patients. Targeted agents – BRAF and MEK inhibitors and immunotherapy improve survival of melanoma patients with BRAF mutations. These agents have intracranial efficacy as shown in clinical trials. However, the efficacy of immunotherapies (immune checkpoint blockade) in melanoma brain metastases and the correlation with BRAF status is not as well characterized. METHODS: We reviewed 351 patients with melanoma brain metastases treated at our tertiary care center between 2000 and 2018, 75 of which received immunotherapy with known BRAF mutational status. Two-year, 5-year, and median overall survival (OS) was calculated from the start of immunotherapy to compare the efficacy of immunotherapy in BRAF mutant and BRAF wild type patients using the log-rank test. RESULTS: At the time of diagnosis of brain metastasis, the median age was 61 (23–87) years, median KPS was 80 (50–100), number of intracranial lesions was 2 (1–15), and 79% had extra-cranial metastases. Sixty-three patients were treated with stereotactic radiosurgery (SRS), 27 underwent whole brain radiation (WBRT) and 21 underwent surgery. When treated with immunotherapy, BRAF mutant and BRAF wild type median survival was 15.7 months (95% CI=9.4 – 42.4) and 6.9 (95% CI=4.1– 26.7) months (p-value=0.205), respectively. Two-year BRAF mutant and BRAF wild type survival was 35% (95% CI=21 – 58) and 28% (95% CI=16 – 51), and 5-year survival was 22% (95% CI=10 – 46) and 23% (95% CI=11 – 47), respectively. CONCLUSIONS: Twenty percent of patients with BRAF mutant and BRAF wild-type patients treated with immunotherapy derive a long-term benefit from immunotherapy and multimodality treatment and are alive 5 years from diagnosis of brain metastases. This was rarely seen in the pre-immunotherapy era in melanoma brain metastases. There was no difference in outcome based on the BRAF mutational status with use of immunotherapy in melanoma brain metastases.

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Association of activating NOTCH1 mutations in adenoid cystic carcinoma with shorter progression-free survival to systemic therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.6089 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 6089-6089 ◽

Cited By ~ 1

Author(s):

Renata Ferrarotto ◽

Alper H Duran ◽

Wei Wei ◽

Brett W. Carter ◽

Adel K. El-Naggar ◽

...

Keyword(s):

Systemic Therapy ◽

Molecular Profile ◽

Rank Test ◽

Analysis Tool ◽

Line Treatment ◽

Wild Type ◽

First Line ◽

The Impact ◽

Notch1 Mutations ◽

First Line Treatment

6089 Background: We previously reported that activating NOTCH1 mutations occurs in approximately 20% of ACCs and drive a phenotype with solid histology, liver and bone metastases, poor prognosis, and potential responsiveness to Notch1 inhibitors; however the impact of NOTCH1mutations on responsiveness to systemic therapy in ACC is unknown. The aim of this study was to evaluate the ORR and median PFS (mPFS) to systemic therapy in patients with metastatic ACC according to their Notch1 status. Methods: We identified 20 ACC patients with measurable disease that underwent treatment at MDACC and had tumor molecular profile. A radiologist blinded to the patient’s NOTCH1status performed review of all images. Measurement of target lesions was captured by a quantitative imaging analysis tool for ORR assessment by RECIST 1.1. PFS was estimated by Kaplan-Meier method. Comparisons of PFS between groups were performed using log-rank test. P≤0.05 was considered statistically significant. Results: Out of 20 patients, 4 (20%) were NOTCH1 mutant. Notch1 pathway activation status by immunohistochemistry (NICD) was available for 15 patients, 10 were positive. The median number of therapy lines was 2 (range 1-6). Best ORR among 49 treatment plans across all lines of systemic therapy including chemotherapy (15), anti-EGFR (10), anti-VEGFR (11), and others (13) was PR in 2 (4%), SD in 29 (59%), and PD in 18 (37%). During first line treatment, patients with NOTCH1 mutations had significantly shorter mPFS compared to NOTCH1 wild-type (2.97 vs. 6.92 months, P = 0.02). The PFS rate at 3 months was 25% for NOTCH1mutants vs. 81% for wild-type. A trend towards shorter PFS was seen in NICD positive vs. negative (3.58 vs. 6.74 months, P = 0.2). Conclusions: NOTCH1 mutations in ACC are associated with shorter PFS during first-line treatment. Validation of these findings is warranted in larger patient cohorts.

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Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases

Scientific Reports ◽

10.1038/s41598-021-97566-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Adam Lauko ◽

Rupesh Kotecha ◽

Addison Barnett ◽

Hong Li ◽

Vineeth Tatineni ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Checkpoint Inhibitors ◽

Tertiary Care ◽

Local Treatment ◽

Cox Proportional Hazards Model ◽

Rank Test ◽

Mutational Status ◽

One Year ◽

The Impact

AbstractImmune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICIs within 90 days of NSCLCBM diagnosis (ICI-90) and compared them to patients who never received ICIs (no-ICI). We reviewed 800 patients with LCBM who were diagnosed between 2010 and 2019 at a major tertiary care institution, 97% of whom received stereotactic radiosurgery (SRS) for local treatment of BM. OS from BM was compared between the ICI-90 and no-ICI groups using the Log-Rank test and Cox proportional-hazards model. Additionally, the impact of KRAS mutational status on the efficacy of ICI was investigated. After accounting for known prognostic factors, ICI-90 in addition to SRS led to significantly improved OS compared to no-ICI (12.5 months vs 9.1, p < 0.001). In the 109 patients who had both a known PD-L1 expression and KRAS status, 80.4% of patients with KRAS mutation had PD-L1 expression vs 61.9% in wild-type KRAS patients (p = 0.04). In patients without a KRAS mutation, there was no difference in OS between the ICI-90 vs no-ICI cohort with a one-year survival of 60.2% vs 54.8% (p = 0.84). However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients. Additionally, this benefit appears to be observed primarily in patients with KRAS mutations that may drive the overall benefit, which should be taken into account in the development of future trials.

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RNF43 mutations to predict survival from treatment with immune checkpoint inhibitors and are associated with a high tumor mutation burden in bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16528 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16528-e16528

Author(s):

Liping Li ◽

Mengmei Yang ◽

Mengli Huang

Keyword(s):

Bladder Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Negative Regulator ◽

Wilcoxon Test ◽

Wild Type ◽

Tumor Mutation Burden ◽

Mutation Burden ◽

The Impact

e16528 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1/L1 have been approved as first-line treatment for cisplatin-ineligible patients and as second-line therapy for patients with metastatic urothelial carcinoma of the bladder. Biomarkers can help select patients who are more likely to response to ICIs. RNF43 is an E3 ubiquitin ligase that acts as a negative regulator of Wnt/β-catenin signaling pathway. In colorectal cancer (CRC) patients treated with immune checkpoint inhibitors (ICIs), RNF43 mutations predicted longer overall survival (OS). The impact of RNF43 mutations on the efficiency of ICIs in bladder cancer(BLC) remains to be explored. Methods: We downloaded the mutation and clinical data of 211 BLC patients treated with ICIs from the immunotherapeutic cohort published by Samstein et al. (2019). OS analyses were conducted using Kaplan-Meier curves and log-rank tests. Wilcoxon test was used for the comparison of TMB. We also downloaded a TCGA cohort for prognostic analysis. The correlations between RNF43 and immune infiltrates were analyzed in the TIMER2.0 database. Statistical significance was set at p = 0.05. Results: RNF43 mutations were identified in 4.3%(9/211) and 3%(13/438) BLC patients in the immunotherapeutic and TCGA cohort, respectively. In the immunotherapeutic cohort, patients with RNF43 mutations had significantly longer OS (25 months vs 8 months; p = 0.015) and higher tumor mutation burden(TMB, 42.3 vs 7.9; p = 3.15E-06) than RNF43-wild-type patients. Different from this, no significant difference was found in OS between RNF43-mutant and RNF43-wild-type BLC patients with standard treatment in the TCGA cohort (p = 0.696). These results indicated that RNF43 was not a prognostic factor but a predictive biomarker of survival in BLC treated with ICIs. No difference was observed in subsets of immune cells between RNF43-mutant and the RNF43-wide-type BLC patients, including neutrophils, macrophages, CD8+ T cells, Tregs, B cells and NK cells. Conclusions: RNF43 mutations may be a predictor of survival benefit from ICIs in bladder cancer and correlated with higher TMB. Further studies in other ICI-treated cohorts are needed to confirm these results.

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Evaluation of different MET genotypes as biomarkers for immunotherapy outcomes in NSCLC patients.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21032 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21032-e21032

Author(s):

Xuanzong Li ◽

Linlin Wang

Keyword(s):

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Rank Test ◽

Wild Type ◽

Exact Test ◽

Entire Cohort ◽

Kaplan Meier ◽

Tumor Mutational Burden ◽

The Difference ◽

Nsclc Patients

e21032 Background: Previous studies suggested that MET exon 14 ( METex14) mutation regarding as a distinct subset was sensitive to MET-inhibitors, but poorly response to immunotherapy. Conversly, MET non-exon-14 (non-ex14) mutations including those undetermined functions and affecting the kinase or extracellular domains were found to be associated with the resistance to MET-inhibitors. However, therapeutic strategies for MET-non-ex14 mutant cancer are still largely unknown, and the relationship between MET-non-ex14 mutations and the efficacy of immune checkpoint inhibitors (ICIs) has never been reported. Using two public ICIs-treated cohorts, we aimed to assess the role of MET mutations including both METex14 and MET-non-ex14 mutations in NSCLC patients undergoing ICIs therapy. Methods: A total of 385 ICIs-treated NSCLC patients were enrolled to our study. MET mutations were defined as any nonsynonymous mutations, and we divided them into METex14 and MET-non-ex14 mutation subsets according to the mutated-position on MET. Kruskal-Wallis test was used to analyze the difference of tumor mutational burden (TMB) score, and the Fisher’s exact test was applied to compare the rates of durable clinical benefit (DCB). Log-rank test was used to analyze the differences between Kaplan-Meier survival curves. Results: In the entire cohort, we found that 17 patients (17/385, 4.4%) had MET mutations, most of which were pure METex14 mutations (10/17, 58.8%). The median TMB of patients in the entire NSCLC cohort was 6.89 mut/Mb. MET-non-ex14 mutant patients (7/385, 1.8%) possessed a significantly higher TMB than METex14-mutant (10/385, 2.6%) and MET wild-type (368/385, 95.6%) sub-cohorts, respectively (median TMB, 17.92 mut/Mb versus 4.17 mut/Mb, p = 0.008; 17.92 mut/Mb versus 6.96 mut/Mb, p = 0.01, respectively). DCB was more common in patients harbored MET-non-ex14 mutations than patients with METex14 mutations and MET wild-type (66.7% versus 14.3%, p = 0.103; 66.7% versus 29.9%, p = 0.075, respectively). We found that patients with MET-non-ex14 mutations had a numerically longer progression free survival (PFS) than those with METex14 mutations and MET wild-type (p = 0.169). Moreover, the PFS was significantly longer in MET-non-ex14-mutant subgroup than patients with METex14 mutations (median PFS, 9.1 versus 2.1 months, p = 0.025). Correspondingly, the overall survival (OS) was significantly longer in MET-non-ex14-mutant subgroup than their wild-type counterparts (median OS, not reached versus 11 months, p = 0.039). Additionally, patients with MET-non-ex14 mutations exhibited relatively better OS versus METex14-mutant patients (median OS, not reached versus 18 months, p = 0.175). Conclusions: MET-non-ex14 mutations were associated with higher TMB, improved DCB rate, and could act as a favorable prognostic biomarker in ICIs-treated NSCLC patients.

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CMET-18. IMPACT OF KRAS MUTATION STATUS ON THE EFFICACY OF IMMUNOTHERAPY IN LUNG CANCER BRAIN METASTASES

Neuro-Oncology ◽

10.1093/neuonc/noz175.219 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi55-vi55

Author(s):

Adam Lauko ◽

Assad Ali ◽

Soumya Sagar ◽

Addison Barnett ◽

Hong Li ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastasis ◽

Brain Metastases ◽

Checkpoint Inhibitors ◽

Care Center ◽

Tertiary Care ◽

Wild Type ◽

Chi Square ◽

Kras Mutations ◽

Mutational Status

Abstract BACKGROUND Immunotherapy is increasingly used in patients with non-small cell lung cancer brain metastases (NSCLCBM). KRAS mutations are associated with worse prognosis and there is no FDA approved targeted therapy. KRAS mutations are associated with increased expression of PD-L1. We evaluated the outcomes of NSCLCBM with KRAS mutations treated with immune checkpoint inhibitors (ICI). METHODS We reviewed 800 patients with NSCLCBM treated at our tertiary care center. 226 had known KRAS mutational status, 121 of which received immunotherapy. Overall survival (OS) was calculated from either the start of immunotherapy (when both groups received immunotherapy) or from the date of diagnosis of brain metastasis. Kaplan-Meier method and Cox Proportional hazard model were utilized to determine differences in OS and the Chi-square test was utilized to determine differences in PD-L1 expression. RESULTS In 109 patients where both KRAS and PD-L1 status were known, KRAS mutations had greater PD-L1 expression (80.1% vs 61.9% positive, p=0.04). There was no difference in OS between KRAS mutant vs KRAS wild-type patients treated with immunotherapy. Median survival from the start of immunotherapy was 15.6 vs 15.5 months respectively (p=0.7), after adjusting for age, KPS, lesion number and extra-cranial metastasis (HR = .91, p=.7). Patients with KRAS mutations treated with immunotherapy versus those who received chemotherapy had a 1-year OS from the diagnosis of brain metastasis of 60.9% vs 38.7% respectively (trending towards significance, p=0.05). KRAS wild-type patients treated with immunotherapy versus those who did not receive immunotherapy had a 1-year OS from the diagnosis of brain metastasis of 61.9% vs 62.5% (p=0.85), respectively. DISCUSSION KRAS mutations are associated with increased PD-L1 expression. Use of immunotherapy negates the poor outcomes seen traditionally in patients with NSCLCBM and KRAS mutations and it improves survival compared to use of chemotherapy. Our experience supports the use of immunotherapy in these patients.

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Systemic Therapy for Melanoma: ASCO Guideline

Journal of Clinical Oncology ◽

10.1200/jco.20.00198 ◽

2020 ◽

Vol 38 (33) ◽

pp. 3947-3970 ◽

Cited By ~ 14

Author(s):

Rahul Seth ◽

Hans Messersmith ◽

Varinder Kaur ◽

John M. Kirkwood ◽

Ragini Kudchadkar ◽

...

Keyword(s):

Systematic Review ◽

Systemic Therapy ◽

Cutaneous Melanoma ◽

Meta Analysis ◽

Mek Inhibitor ◽

Wild Type ◽

Additional Information ◽

Metastatic Setting ◽

Wide Range ◽

Braf Mutant

PURPOSE To provide guidance to clinicians regarding the use of systemic therapy for melanoma. METHODS ASCO convened an Expert Panel and conducted a systematic review of the literature. RESULTS A systematic review, one meta-analysis, and 34 additional randomized trials were identified. The published studies included a wide range of systemic therapies in cutaneous and noncutaneous melanoma. RECOMMENDATIONS In the adjuvant setting, nivolumab or pembrolizumab should be offered to patients with resected stage IIIA/B/C/D BRAF wild-type cutaneous melanoma, while either of those two agents or the combination of dabrafenib and trametinib should be offered in BRAF-mutant disease. No recommendation could be made for or against the use of neoadjuvant therapy in cutaneous melanoma. In the unresectable/metastatic setting, ipilimumab plus nivolumab, nivolumab alone, or pembrolizumab alone should be offered to patients with BRAF wild-type cutaneous melanoma, while those three regimens or combination BRAF/MEK inhibitor therapy with dabrafenib/trametinib, encorafenib/binimetinib, or vemurafenib/cobimetinib should be offered in BRAF-mutant disease. Patients with mucosal melanoma may be offered the same therapies recommended for cutaneous melanoma. No recommendation could be made for or against specific therapy for uveal melanoma. Additional information is available at www.asco.org/melanoma-guidelines .

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Controlling Nutritional Status (CONUT) Score is Associated with Overall Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib: A Multicenter Cohort Study

Nutrients ◽

10.3390/nu12041076 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1076 ◽

Cited By ~ 1

Author(s):

Shigeo Shimose ◽

Takumi Kawaguchi ◽

Hideki Iwamoto ◽

Masatoshi Tanaka ◽

Ken Miyazaki ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Nutritional Status ◽

Survival Time ◽

Median Survival ◽

Median Survival Time ◽

Rank Test ◽

Multicenter Cohort Study ◽

The Impact ◽

Conut Score

We aimed to investigate the impact of the controlling nutritional status (CONUT) score, an immuno-nutritional biomarker, on the prognosis of patients with hepatocellular carcinoma (HCC) treated with lenvatinib (LEN). This retrospective study enrolled 164 patients with HCC and treated with LEN (median age 73 years, Barcelona Clinic Liver Cancer (BCLC) stage B/C 93/71). Factors associated with overall survival (OS) were evaluated using multivariate and decision tree analyses. OS was calculated using the Kaplan–Meier method and analyzed using the log–rank test. Independent factors for OS were albumin–bilirubin grade 1, BCLC stage B, and CONUT score <5 (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.58–5.31, p < 0.001). The CONUT score was the most important variable for OS, with OS rates of 70.0% and 29.0% in the low and high CONUT groups, respectively. Additionally, the median survival time was longer in the low CONUT group than in the high CONUT group (median survival time not reached vs. 11.3 months, p < 0.001). The CONUT score was the most important prognostic variable, rather than albumin–bilirubin grade and BCLC stage, in patients with HCC treated with LEN. Accordingly, immuno-nutritional status may be an important factor in the management of patients with HCC treated with LEN.

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CMET-23. IMPACT OF SYSTEMIC THERAPY IN MELANOMA BRAIN METASTASIS

Neuro-Oncology ◽

10.1093/neuonc/noz175.224 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi56-vi56

Author(s):

Soumya Sagar ◽

Adam Lauko ◽

Addison Barnett ◽

Wei (Auston) Wei ◽

Samuel Chao ◽

...

Keyword(s):

Targeted Therapy ◽

Brain Metastasis ◽

Brain Metastases ◽

Systemic Therapy ◽

Checkpoint Inhibitors ◽

Care Center ◽

Performance Status ◽

Tertiary Care ◽

P Value ◽

Surgical Removal

Abstract BACKGROUND Melanoma is the third most common malignancy that results in brain metastasis and is associated with a median overall survival (OS) of approximately 9 months. In recent years, management of melanoma brain metastases (MBM) by surgery and radiation [stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT)] has been bolstered by targeted therapy and immune checkpoint inhibitors (ICI). METHODS 351 patients, treated for MBM at our tertiary care center from 2000–2018, were grouped into: received chemotherapy, ICI, or targeted therapy. 34% of patients treated with ICI had received other systemic therapies as well as part of their management. OS was calculated from the date of diagnosis of the brain metastases. The Kaplan Meier analysis was utilized to determine median OS and difference in OS was determined by utilizing the Cox proportional hazard model. RESULTS The median survival after the diagnosis of brain metastasis was 10.4, 11.96, and 7.06 months in patients who received ICI, chemotherapy and targeted therapy respectively. A multivariate model was developed including the type of systemic therapy, presence of extracranial metastases, age, KPS and number of intracranial lesions. 114 patients underwent SRS alone, 56 underwent SRS and WBRT, 43 underwent SRS and surgical removal, 28 had surgical removal, SRS and WBRT, and 78 had no intracranial therapy. Compared to patients who received chemotherapy, patients who received immunotherapy had a hazard ratio, HR = 0.628 (confidence interval = 0.396 – 0.994, p-value = 0.047). Presence of EC metastases (HR= 1.25, p-value < .001), lower KPS (HR = .97, p-value < .0001) and multiple brain lesions (HR = 1.117, p-value < .0001) were associated with significantly worse OS. CONCLUSIONS Addition of ICI significantly improves the OS in MBM compared to chemotherapy. Lower performance status, multiple brain metastases, and EC metastases are associated with poor OS.

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