Single-institution outcomes with less than two-year anti-PD-1 antibody therapy in metastatic melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22001-e22001
Author(s):  
Tsering G. Lama Tamang ◽  
John P. Fruehauf ◽  
Samuel Ejadi
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Antibody Therapy ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Single Institution ◽  
Antibody Treatment ◽  
Clinical Criteria ◽  
Number Of Patients

e22001 Background: Optimal duration of anti-PD-1 antibody therapy remains undefined. Currently, treatment is given up to two years in metastatic melanoma based on clinical trials. However, recent observations suggest that anti-PD-1 antibodies may work as well if given for shorter time periods. To better understand duration of anti-PD-1 antibody treatment, we reviewed outcomes for patients who discontinued immunotherapy earlier than 2 years in our Cancer Center. Methods: This is a retrospective, single-institution review of metastatic melanoma patients who received anti-PD-1 antibodies from January 2010 to December 2019. We further identified the patients discontinuing treatment before completion of 2 years for reasons other than disease progression. Duration was categorized into three groups: < 6 months (A), 6-12 months (B) and > 12 months (C) and outcomes were analyzed. Progression free survival (PFS) was defined as the time from the initiation of anti-PD1-therapy to the date of progression as determined by treating physician based on radiological, biochemical and/or clinical criteria. Results: 25 patients with mean age 69 years (49-91; N = 19 > 60yo) were identified. Number of patients who received anti-PD-1 antibodies were N = 8, N = 9 and N = 8 in in groups A, B and C respectively. 44% of patients discontinued treatment after achieving either partial or near complete remission, whereas the remaining 66% of patients discontinued treatment due to adverse events. Majority of patients who stopped treatment due to adverse events were older than 60 (71.4%). In 29 months of median follow up (range 11-54), none of patients who received treatment in group B progressed, whereas in groups A and C, 25% percentage progressed in each group with 80% PFS at 12.8 months and 88% PFS at 26 months respectively. 12.5% of patients in group A had progression at 12 months follow up, where no progression was noticed in groups B and C during the same time period. Conclusions: Retrospective analysis of our experience supports other retrospective findings that treatment with anti-PD-1 antibodies more than 12 months might not add further benefit in responding or non-progressing older patients though further study with longer follow up is required.

Comparison of the frequency of adverse events requiring interventions determined by telephone follow up in hepatocellular carcinoma patients treated with sorafenib and lenvatinib.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 507-507
Author(s):  
Koki Morishita ◽  
Hidetaka Suzuki ◽  
Junko Tauchi ◽  
Misaki K Takeno ◽  
Kohei Hayashi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Treatment Withdrawal ◽  
Cancer Center ◽  
First Line ◽  
Sorafenib Treatment ◽  
Number Of Patients ◽  
Center Hospital ◽  
Hand Foot Syndrome

507 Background: The REFLECT trial demonstrated that lenvatinib is non-inferior to sorafenib for first-line treatment of unresectable hepatocellular carcinoma (uHCC). However, no comparison of the frequency of adverse events (AEs) requiring interventions has been reported yet between uHCC patients receiving sorafenib and those receiving lenvatinib. At the National Cancer Center Hospital East, Japan, pharmacists conduct telephone follow-up (TF) during the first month after the start of treatment with sorafenib or lenvatinib in uHCC patients, for the purpose of detecting and treating AEs early. The aim of this study was to reveal the frequency of AEs requiring interventions between patients receiving sorafenib and those receiving lenvatinib, based on TF. Methods: The characteristics, AEs and contents of intervention by TF of 56 uHCC patients who had been started on treatment with sorafenib and lenvatinib were reviewed retrospectively. The study subjects were 33 patients initiated on sorafenib treatment and monitored by TF from March 2017 to March 2018 (Group S) and 23 patients initiated on lenvatinib treatment and monitored by TF from March 2018 to March 2019 (Group L). Results: The total numbers of TFs in Group S and Group L were 91 and 48, respectively. The rate of AEs requiring interventions was significantly higher in Group S as compared to Group L (Group S, 17.6% (16/91); Group L, 4.2% (2/48); p = 0.032). The frequencies of the interventions, including use of supportive treatments (A), withdrawal of sorafenib or lenvatinib (B), and medical examination (C), differed between the two groups (A/B/C: Group S, 8/5/3 times vs. Group L, 2/0/0 times). The most frequently observed AE that necessitated intervention in Group S was the hand-foot syndrome (HFS) (75.0%, 12/16). Conclusions: The frequency of interventions for AEs appears to be higher in uHCC patients receiving sorafenib than in those receiving lenvatinib. Although a great number of patients taking sorafenib had symptomatic AEs, such as HFS, early detection of the symptoms through TF contributed to prevention of treatment withdrawal on account of AEs.

Multicentric ipilimumab experience in Turkish patients with metastatic melanoma: MIPI-TURK at 30 months of follow-up.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20006-e20006
Author(s):  
Alper Sevinc ◽  
Hande Turna ◽  
Mustafa Ozdogan ◽  
Suleyman Buyukberber ◽  
Gokhan Demir ◽  
...  
Keyword(s):  
Overall Survival ◽  
Side Effects ◽  
Adverse Events ◽  
Metastatic Melanoma ◽  
Muscle Weakness ◽  
Progression Free Survival ◽  
Survival Duration ◽  
Response Evaluation ◽  
Melanoma Patients

e20006 Background: Ipilimumab, an anti-CTLA-4 (cytotoxic T lymphocyte-associated antigen) monoclonal antibody has been shown to enhance immune responses and improve overall survival in patients with metastatic melanoma. The authors report retrospectively on metastatic melanoma patients treated under the Expanded Access Program in Turkey among 13 centers. Methods: Patients with metastatic melanoma were treated with ipilimumab 3 mg/kg every 3 week for 4 doses. Response evaluation was done on week 12. Patients with complete response (CR), partial response (PR), and stable disease (SD) at week 12 were eligible for re-treatment. Results: A total of 97 patients enrolled with 77 evaluable. Ipilimumab treatment was given as 2nd (20.0%), 3rd (64.3%), and 4th(15.7%) line. The rate of the patients receiving ipilimumab for 1, 2, 3, and 4 doses were 5.2%, 11.7%, 16.9%, and 62.3%, respectively. Seven of 77 patients were eligible for re-treatment. G1/2, G3/4, and G5 adverse events were reported in 23.4% (18/77), 14.3% (11/77), and 2.6% (2/77) of the patients, respectively. The most common G1/2 immune related adverse events were rash (14.3%), muscle weakness (10.0%), and gastrointestinal side effects (8.6%). There were seven G3 side effects (diarrhea in 4, muscle weakness in 1, hypothyroidism in 1, and GI bleeding in 1 patient) and four G4 side effects (thrombocytopenia in 1, diarrhea in 1, sinus tachycardia in 1, and multiple organ failure in 1 patient). Two deaths (G5) were associated with hepatic AEs. Regarding the response evaluation, there was no CR within 16 months of follow-up period and the median overall progression free survival duration was 2 months (95% CI, 1.6-2.5). The disease control rate was 38.8% (PR: 16.3% and SD: 22.5%). Median time to progression was 2 months (95% CI, 1.8-3.1 months). Of the patients, 31.9%, 22.2%, and 19.2% survived within 12, 24, and 30 months of follow-up period, respectively, and the median overall survival duration was 6 months (95% CI, 3.5-8.5). Conclusions: Ipilimumab treatment resulted in favorable clinical benefit for metastatic melanoma patients. Data generated by 13 centers revealed an efficacy and safety profile consistent with the currently available ipilimumab trials.

The Activity of Taxanes in the Treatment of Sex Cord-Stromal Ovarian Tumors

2004 ◽  
Vol 22 (17) ◽  
pp. 3517-3523 ◽  
Author(s):  
Jubilee Brown ◽  
Hyun S. Shvartsman ◽  
Michael T. Deavers ◽  
Thomas W. Burke ◽  
Mark F. Munsell ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Complete Response ◽  
Cancer Center ◽  
First Line ◽  
Stromal Tumors ◽  
Number Of Patients ◽  
Measurable Disease ◽  
Line Setting ◽  
Sex Cord Stromal Tumors

Purpose To determine the efficacy and side effects of taxanes, with or without platinum, for the treatment of sex cord-stromal tumors of the ovary. Patients and Methods We conducted a retrospective review of all patients seen from 1985 to 2002 at The University of Texas M.D. Anderson Cancer Center with ovarian sex cord-stromal tumors. Eligible patients underwent pathology confirmation and clinical evaluation at M.D. Anderson and received a taxane for initial or recurrent disease. Results Of 222 patients identified, 44 were eligible for analysis. For nine patients treated in the first-line adjuvant setting, median progression-free survival (PFS) was not reached at 51 months. Of two patients treated for measurable disease in the first-line setting, one had a complete response. Median PFS was 34.3 months; median overall survival (OS) was not reached. Median follow-up was 90.3 months (range, 39.4 to 140.5 months). Response rate for 30 patients treated with a taxane ± platinum for recurrent, measurable disease was 42%. Median PFS was 19.6 months; median OS was not reached. Median follow-up was 100.7 months (range, 8.1 to 361.3 months). The presence of platinum correlated with response in the recurrent, measurable disease setting. The number of patients was insufficient to detect relative efficacy of paclitaxel and docetaxel. Adverse effects of paclitaxel included neutropenia (n = 6), anemia (n = 1), thrombocytopenia (n = 1), myelodysplasia (n = 1), and hypersensitivity (n = 1). Conclusion Taxanes seem to be active agents in the treatment of patients with sex cord-stromal tumors of the ovary. The combination of taxanes with platinum in the treatment of this disease deserves additional investigation.

scholarly journals Durable responses in patients with genitourinary cancers following immune checkpoint therapy rechallenge after moderate-to-severe immune-related adverse events

2021 ◽  
Vol 9 (7) ◽  
pp. e002850
Author(s):  
Bilal A Siddiqui ◽  
Jinesh S Gheeya ◽  
Rohit Goswamy ◽  
Tharakeswara K Bathala ◽  
Devaki Shilpa Surasi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Duration ◽  
Response Rates ◽  
Complete Response ◽  
Cancer Center

BackgroundImmune checkpoint therapy (ICT) prolongs survival in subsets of patients with cancer but can also trigger immune-related adverse events (irAEs) requiring treatment discontinuation. Recent studies have investigated safety of ICT rechallenge after irAEs, and evidence suggests that rechallenge may be associated with improved antitumor responses. However, data are limited on response duration after ICT rechallenge, particularly after severe irAEs.ObjectiveTo evaluate safety and efficacy of ICT rechallenge after moderate-to-severe irAEs in patients with renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer.MethodsIn this retrospective cohort study, medical records from September 25, 2013, to June 1, 2020, for patients with genitourinary (GU) cancers at MD Anderson Cancer Center who were rechallenged with the same or different ICT following irAEs were reviewed. Demographics, ICT exposure, irAEs (grade and treatment), ICT discontinuation or rechallenge, rates of subsequent irAEs (new or recurrent) and antitumor activity (objective response rates and response duration) were reviewed.ResultsSixty-one patients with RCC, UC, and prostate cancer were rechallenged with ICT after experiencing 105 total irAEs. Objective response rates after rechallenge, that is, upgrade in response, were 14% in RCC (4/28), 21% in UC (3/14), and 0% in prostate cancer. All seven patients who achieved upgrade in response had initial grade 2 or 3 irAEs. Responses were durable among these seven patients, with median radiographic progression-free survival not reached (range: 3.7–66.4 months) as of the March 8, 2021, data cut-off (median follow-up 40.9 months (95% CI 35.3 to 46.5)). All achieved complete response except one patient who was lost to follow-up. The rate of subsequent grade 3 or 4 irAEs after rechallenge was 30%, with no fatal irAEs. The rate of recrudescence of the same irAE was 26% (16/61). 54% of patients received corticosteroids (33/61), and 21% received targeted immunosuppression (13/61) for the initial irAEs.Conclusions and relevanceICT rechallenge after moderate-to-severe irAEs was associated with deep and durable responses in a subset of patients with RCC and UC, with acceptable safety and no fatal events. Strategies to enable ICT resumption after moderate-to-severe irAEs, such targeted immunosuppression, warrant further study.

scholarly journals SAT0540 ONE-YEAR OUTCOMES AFTER RHEUMATIC IMMUNE-RELATED ADVERSE EVENTS FROM CHECKPOINT INHIBITORS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1227.2-1227
Author(s):  
E. Berard ◽  
T. Barnetche ◽  
L. Rouxel ◽  
C. Dutriaux ◽  
L. Dousset ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Symptomatic Treatment ◽  
Musculoskeletal Symptoms ◽  
Day Range ◽  
One Year

Background:Description and initial management of rheumatic immune-related adverse-events (irAEs) from cancer immunotherapies have been reported by several groups but to date, few studies have evaluated the long-term outcomes and management of rheumatic irAEs (1).Objectives:To describe the long-term management and assess the one-year outcomes of patients who experienced rheumatic immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI).Methods:This was a single-centre prospective observational study including patients referred for musculoskeletal symptoms while treated with ICI. After baseline rheumatological evaluation defining the clinical entity presented, follow-up visits were organised according to the type and severity of irAE. At one year, persistence of irAE, ongoing treatment, as well as cancer outcomes were assessed.Results:63 patients were included between September 2015 and June 2018. 24 patients (38%) presented with non-inflammatory musculoskeletal conditions managed with short-term symptomatic treatment and did not require specific follow-up. 39 patients (62%) experienced inflammatory manifestations, mimicking either rheumatoid arthritis (RA, n=19), polymyalgia rheumatica (PMR, n=16), psoriatic arthritis (PsA, n=3) and one flare of a preexisting axial spondyloarthritis. Overall, 32 patients (82%) received systemic glucocorticoids, with a median rheumatic dosage of 15mg/day (range: 5-60mg/day). None of the patients had to permanently discontinue ICI therapy for rheumatic irAE. 20 patients (67%) were still receiving glucocorticoids at one year, with a median dosage of 5mg/day (range: 2-20mg/day). Glucocorticoids were more frequently discontinued for patients with RA-like condition (44%) than PMR-like condition (23%), but no other predictive factor of glucocorticoids withdrawal could be identified. At one year, overall survival and progression-free survival were comparable between patients who were still receiving glucocorticoids for rheumatic irAE and patients who have discontinued. Eight patients required csDMARDs.Conclusion:At one year, a majority of patients required long-term low-dose glucocorticoids for chronic rheumatic irAE, which seems not altering oncological control.References:[1]Braaten TJ, Brahmer JR, Forde PM, et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Ann Rheum Dis. 2019 Sep 20.Disclosure of Interests:None declared

Evolution of Surgical Approaches in the Treatment of Petroclival Meningiomas: A Retrospective Review

2007 ◽  
Vol 61 (suppl_5) ◽  
pp. ONS202-ONS211 ◽  
Author(s):  
Nicholas C. Bambakidis ◽  
U. Kumar Kakarla ◽  
Louis J. Kim ◽  
Peter Nakaji ◽  
Randall W. Porter ◽  
...  
Keyword(s):  
Survival Rates ◽  
Progression Free Survival ◽  
Surgical Approaches ◽  
Single Institution ◽  
Short Term ◽  
Total Resection ◽  
Free Survival ◽  
Petroclival Meningioma ◽  
Petroclival Meningiomas

Abstract Objective: We examined the surgical approaches used at a single institution to treat petroclival meningioma and evaluated changes in method utilization over time. Methods: Craniotomies performed to treat petroclival meningioma between September of 1994 and July of 2005 were examined retrospectively. We reviewed 46 patients (mean follow-up, 3.6 yr). Techniques included combined petrosal or transcochlear approaches (15% of patients), retrosigmoid craniotomies with or without some degree of petrosectomy (59% of patients), orbitozygomatic craniotomies (7% of patients), and combined orbitozygomatic-retrosigmoid approaches (19% of patients). In 18 patients, the tumor extended supratentorially. Overall, the rate of gross total resection was 43%. Seven patients demonstrated progression over a mean of 5.9 years. No patients died. At 36 months, the progression-free survival rate for patients treated without petrosal approaches was 96%. Of 14 patients treated with stereotactic radiosurgery, none developed progression. Conclusion: Over the study period, a diminishing proportion of patients with petroclival meningioma were treated using petrosal approaches. Utilization of the orbitozygomatic and retrosigmoid approaches alone or in combination provided a viable alternative to petrosal approaches for treatment of petroclival meningioma. Regardless of approach, progression-free survival rates were excellent over short-term follow-up period.

scholarly journals Combined CTLA-4 and PD-L1 blockade in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer is associated with increased myeloid and neutrophil immune subsets in the bone microenvironment

2021 ◽  
Vol 9 (10) ◽  
pp. e002919
Author(s):  
Sumit K Subudhi ◽  
Bilal A Siddiqui ◽  
Ana M Aparicio ◽  
Shalini S Yadav ◽  
Sreyashi Basu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Immune Checkpoints ◽  
Castration Resistant Prostate Cancer ◽  
Bone Microenvironment ◽  
Castration Resistant ◽  
Number Of Patients ◽  
Measurable Disease

BackgroundImmune checkpoint therapy (ICT) has low response rates in patients with metastatic castration-resistant prostate cancer (mCRPC), in part due to few T cells in the tumor microenvironment (TME). Anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) promotes intratumoral T cell infiltration but induces upregulation of PD-1 and programmed death ligand-1 (PD-L1) within the prostate TME. Combined anti-CTLA-4 plus anti-PD-1 can partly overcome this adaptive resistance and was recently shown to augment responses in patients with mCRPC with measurable disease. Although bone is the most common site of metastasis in prostate cancer, patients with bone-predominant disease are frequently excluded from trials because they lack measurable disease, which limits assessment of disease progression and tissue sampling. We therefore designed this study to investigate combined ICT in mCRPC to bone.HypothesisCombined anti-CTLA-4 (tremelimumab) plus anti-PD-L1 (durvalumab) is safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone.Patients and methodsIn this single-arm pilot study, men with chemotherapy-naïve mCRPC to bone received tremelimumab (75 mg intravenous) plus durvalumab (1500 mg intravenous) every 4 weeks (up to four doses), followed by durvalumab (1500 mg intravenous) maintenance every 4 weeks (up to nine doses). The primary endpoint was incidence of adverse events. Secondary endpoints included serum prostate-specific antigen (PSA), progression-free survival (PFS), radiographic PFS (rPFS), and maximal PSA decline.ResultsTwenty-six patients were treated between August 8, 2017 and March 28, 2019. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 11 patients (42%), with no grade 4 or 5 events. TRAEs leading to discontinuation occurred in three patients (12%). PSA decline ≥50% occurred in three patients (12%). Six patients (24%) achieved stable disease for >6 months. At a median follow-up of 43.6 months, median rPFS was 3.7 months (95% CI: 1.9 to 5.7), and median overall survival was 28.1 months (95% CI: 14.5 to 37.3). Post-treatment evaluation of the bone microenvironment revealed transcriptional upregulation in myeloid and neutrophil immune subset signatures and increased expression of inhibitory immune checkpoints.ConclusionsTremelimumab plus durvalumab was safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone, with potential activity in a small number of patients as measured by rPFS. Combination of CTLA-4 and PD-L1 blockade with therapies targeting the myeloid compartment or other inhibitory immune receptors may be necessary to overcome mechanisms of resistance within prostate bone microenvironment.Trial registration numberNCT03204812.

scholarly journals Promising Immunotherapy in Metastatic Testicular Sex Cord Stromal Tumours After First-Line Chemotherapy

2022 ◽  
Vol 12 ◽  
Author(s):  
Bingqing Shang ◽  
Chuanzhen Cao ◽  
Weixing Jiang ◽  
Hongzhe Shi ◽  
Xingang Bi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Chemotherapy Resistance ◽  
Progression Free Survival ◽  
Retroperitoneal Lymph Node Dissection ◽  
First Line ◽  
Experienced Grade ◽  
Line Chemotherapy

BackgroundTesticular sex cord stromal tumours (TSCSTs) are rare, with few studies focusing on the metastatic TSCST prognosis. The value of treatments, including radical orchiectomy (RO) and retroperitoneal lymph node dissection (RPLND), in preventing metastasis is controversial. Additionally, metastatic TSCSTs are resistant to chemotherapy. We aimed to assess the effectiveness and safety of immunotherapy in metastatic TSCSTs after first-line chemotherapy.MethodsWe retrospectively screened patients with testicular tumours undergoing testis surgery between January 2005 and January 2019. Patients with TSCSTs who had undergone testis-sparing surgery (TSS) or RO were identified. The malignant type was defined as metastasis confirmed by pathology. Treatment responses, progression-free survival (PFS), overall survival (OS) and safety were analysed.ResultsAmong the 494 testicular tumour patients who received TSS or RO, 11 (2.2%) patients with histologically proven TSCSTs were identified. At the last follow-up, 7 patients survived without tumours, and 4 patients developed metastasis and received first-line cisplatin-based chemotherapy, with 1 of them achieving an objective response. Their PFS times were 1.5, 2.2, 9.0, and 17.0 months, respectively. Two patients received immune checkpoint inhibitors (ICIs) after developing chemotherapy resistance and achieved a partial response up to the last follow-up; one of them experienced Grade 1 adverse events, and the other experienced Grade 2 adverse events during immunotherapy. The median OS time of the 4 patients with metastatic TSCSTs was 32 months.ConclusionsTSCSTs are rare, and most are benign with a good prognosis. ICIs represent a promising option for improving clinical outcomes in metastatic TSCSTs.

Efficacy of the PD-L1 inhibitor avelumab in neuroendocrine or aggressive variant prostate cancer: Results from a phase II, single-arm study.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 89-89
Author(s):  
Landon Carter Brown ◽  
Susan Halabi ◽  
Michael Sandon Humeniuk ◽  
Yuan Wu ◽  
Taofik Oyekunle ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Liver Metastasis ◽  
Adverse Events ◽  
Phase Ii ◽  
Radiographic Progression ◽  
Progression Free Survival ◽  
High Serum ◽  
Small Cell ◽  
Clinical Criteria ◽  
Aggressive Variant

89 Background: Men with metastatic neuroendocrine/small cell and aggressive variant prostate cancer (NEPC/AVPC) have poor outcomes despite platinum and taxane chemotherapy. These tumors share common features with small cell lung cancer, including higher tumor mutational burden and genomic alterations, and thus may be responsive to immunotherapy. Methods: We conducted a single arm, 2-stage phase II investigator-sponsored trial, (PICK-NEPC, NCT03179410) with the PD-L1 inhibitor avelumab in patients with NEPC/AVPC. NEPC/AVPC was defined either by histologic criteria (neuroendocrine or small cell features) by central pathology review or by aggressive variant clinical criteria (prior progression on abiraterone or enzalutamide with liver metastasis, bulky radiographic progression and low PSA, or high serum LDH). Prior chemotherapy or hormonal therapy was allowed. Avelumab 10 mg/kg IV every 2 weeks was administered until progression or unacceptable toxicity with ongoing ADT. The primary endpoint was overall response rate (ORR) defined by modified PCWG3 and iRECIST criteria. Results: We consented 19 men with AVPC/NEPC, and 15 initiated treatment with avelumab. The median age was 71 (range 51-85), and 27% had neuroendocrine or small cell histology, while 73% met AVPC clinical criteria with adenocarcinoma histology. Men had received a median of two prior systemic therapies (range 1-3) including carboplatin (27%), docetaxel (73%), enzalutamide (67%), and abiraterone (47%). Median PSA was 54 ng/mL (range 0-393) and 73% had liver metastasis. The ORR by iRECIST was 6.7% (95% CI 0-32%) with 1 CR, 0 PRs, 3 (20%) with stable disease, and 11 (73%) with progressive disease. The patient with a CR had NEPC with a CNS metastasis that was found to be MSI-high/TMB-high due to a somatic MSH2 alteration; he finished 12 months of avelumab and maintains a durable CR and undetectable PSA 6 months after completing all therapy including ADT. Median radiographic progression free survival was 1.8 months (95% CI 1.6-2.0 mo) and median time on therapy was 56 days (range 28-356). Median overall survival was 7.4 mo (85% CI 2.8-12.5 mo). Two grade 3 adverse events (abdominal pain due to hepatic disease progression versus immune hepatitis and pericarditis), and one grade 4 (immune hepatitis) adverse event were attributed to avelumab with no grade 5 adverse events. Grade 1 or 2 infusion-related reactions were experienced by 9 (60%). Conclusions: PD-L1 inhibition with avelumab demonstrated limited clinical efficacy in men with metastatic NEPC/AVPC other than in those with MSI-high disease. Further research is needed into mechanisms of immune evasion in NEPC/AVPC to develop novel immunotherapies. Clinical trial information: NCT03179410.

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