Plasma circulating tumor DNA (ctDNA) fraction and real-world overall survival (rwOS) in metastatic castration resistant prostate cancer (mCRPC).

e17035 Background: Assessment of disease burden and severity influences numerous decisions in cancer care yet is not always straightforward. In mCRPC, most patients (pts) have bone-only metastases, for which disease burden quantification by imaging is challenging. Using commercially available assays for comprehensive genomic profiling (CGP), we hypothesized higher levels of ctDNA would associate with worse rwOS in mCRPC. Methods: Pts with mCRPC who received care within Flatiron Health (FH) network between 1/1/2011-6/30/2020 were assessed. Pts had to have FoundationOne Liquid performed ≤60 days prior to initiation of at least one line of therapy (LOT). Clinical characteristics and treatment history were obtained from deidentified, EHR data and linked to genomic data in the FH-Foundation Medicine Clinico-Genomic Database. Univariable and multivariable Cox proportional hazard models were utilized for rwOS comparisons indexed to LOT start, adjusted for LOT, age, and PSA, hemoglobin, alkaline phosphatase, albumin, and recent ECOG status when available. For one pt with two samples, the earlier one was used. Plasma ctDNA levels were quantified using a composite tumor fraction (cTF) measure based on aneuploidy and variant allele fraction (VAF), dichotomized at a previously reported threshold of 10% (Stover et al, JCO, 2018). Association of cTF with rwOS across common solid tumors was then explored in the FH-FMI CGDB for advanced breast cancer (BC), metastatic colorectal cancer (mCRC) and advanced non-small cell lung cancer (aNSCLC). Results: 78 mCRPC pts met criteria with 36 deaths to date. 15 (19%), 19 (24%), 17 (22%) and 27 (35%) samples were respectively obtained prior to first, second, third, or fourth mCRPC LOT, and median PSA was 85.1 ng/mL (IQR: 23.2 – 177). 69/78 (88%) were from community sites. cTF was ≥ 10% in 46/78 samples (60%) and was significantly associated with median PSA (115 vs. 27 ng/mL, p = 0.006) and elevated alk phos (52.2% vs. 12.5%, p < 0.001). Pts with ≥ 10% cTF had significantly worse rwOS (median 6.2 mo vs. not reached, HR: 9.9, 95% CI: 3.0 – 32.4, p < 0.001), which persisted in the multivariable Cox regression (HR: 9.4, 95% CI: 2.4 – 36.4, p = 0.001, n = 65, 13 missing clinical data). Preliminary results in other cancers, adjusted for LOT number only, were consistent with mCRPC; cTF ≥ 10% was associated with a worse rwOS in mBC (n=245, HR: 1.8 CI: 1.1 – 3.0), mCRC (n=107, HR: 2.1 CI: 1.1 – 4.3) and aNSCLC (n=432, HR: 1.8 CI: 1.3 – 2.5). Conclusions: Pretreatment ctDNA level is a prognostic factor in mCRPC in a real-world setting. With prospective validation, cTF may permit identification of high risk pts requiring more aggressive or investigational therapies. This phenomenon may not be unique to mCRPC and could offer similar insights in other cancer types.

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Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US

Annals of Hematology ◽

10.1007/s00277-021-04534-8 ◽

2021 ◽

Author(s):

Faith Davies ◽

Robert Rifkin ◽

Caitlin Costello ◽

Gareth Morgan ◽

Saad Usmani ◽

...

Keyword(s):

Multiple Myeloma ◽

Real World ◽

Comparative Effectiveness ◽

Proteasome Inhibitors ◽

Refractory Multiple Myeloma ◽

Kaplan Meier ◽

The Us ◽

Cox Proportional Hazard Models ◽

Comparative Effectiveness Analysis ◽

Line Of Therapy

AbstractMultiple available combinations of proteasome inhibitors, immunomodulators (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating triplet regimens in line of therapy (LOT) ≥ 2 on/after 1/1/2014 was followed between 1/2007 and 3/2018 in Optum’s deidentified US electronic health records database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; regimens were compared using covariate-adjusted Cox proportional hazard models. Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, n = 349; KRd, n = 218; DRd, n = 99; IRd, n = 154) and 348 patients (392 patient LOTs) with a Pd backbone (VPd, n = 52; KPd, n = 146; DPd, n = 149; IPd, n = 45) in LOTs ≥2 were identified. More patients ≥75 years received IRd (39.6%), IPd (37.8%), and VRd (36.7%) than other triplets. More patients receiving VRd/VPd were in LOT2 vs other triplets. Unadjusted median TTNT in LOT ≥ 2: VRd, 13.9; KRd, 8.7; IRd, 11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. In covariate-adjusted analysis, only KRd vs DRd was associated with a significantly higher risk of next LOT initiation/death (HR 1.72; P = 0.0142); no Pd triplet was significantly different vs DPd in LOT ≥ 2. Our data highlight important efficacy/effectiveness gaps between results observed in phase 3 clinical trials and those realized in the RW.

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Treatment patterns of new metastatic castration-resistant prostate cancer (mCRPC) therapies: Real-world evidence from three datasets.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.228 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 228-228 ◽

Cited By ~ 2

Author(s):

Lorie Ellis ◽

Marie-Helene Lafeuille ◽

Laurence Gozalo ◽

Patrick Lefebvre ◽

Elisabetta Malangone-Monaco ◽

...

Keyword(s):

Real World ◽

Single Agent ◽

Study Drug ◽

Abiraterone Acetate ◽

Castration Resistant Prostate Cancer ◽

Treatment Interventions ◽

Castration Resistant ◽

Community Oncology ◽

Real World Evidence ◽

Line Of Therapy

228 Background: Little information exists regarding the sequences in which new mCRPC therapies with evidence of survival benefits are used. This study aims at describing the sequence of mCRPC medication use as observed in 3 healthcare datasets. Methods: Healthcare claims datasets (Dataset #1 and #2) and a community oncology electronic medical record (Dataset #3) were used to identify PC patients with ≥ 1 claim for a study drug (abiraterone acetate--AA, cabazitaxel--CAB, docetaxel – DOC, enzalutamide – ENZ, and sipuleucel T – SIP) occurring after 9/1/2012. The index date was the 1st study drug claim. Patients were excluded if a study drug claim occurred prior to 9/1/2012. Descriptive statistics summarized the proportion of patients receiving one vs. two or more lines of therapy. The prevalence of 1st line therapy and of 1st to 2nd-line sequences was analyzed. Results: Analysis of 3 unique datasets with > 5,900 PC patients revealed most patients received a single line of therapy. AA and DOC were the most common 1st line agents. The five most-prevalent 1st- to 2nd-line sequences identified in each database are shown in the table below. The most commonly observed 1st- to 2nd-line sequences were AA-ENZ, AA-DOC, and DOC-AA. Conclusions: Real world treatment selection for 5 mCRPC medications was consistent across 3 datasets. The majority of PC patients had a prescription/claim for a single agent. AA and DOC were the most commonly selected 1st line treatments. A 2nd-line agent was observed in 14-33% of patients. Similar patterns of 1st-2nd line sequences were observed between datasets. Further research is warranted with longer follow-up and consideration of other treatment interventions. [Table: see text]

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P1.16-04 Real World Experience of Using Comprehensive Genomic Profiling of Plasma Circulating Tumor DNA

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2019.08.1230 ◽

2019 ◽

Vol 14 (10) ◽

pp. S586-S587

Author(s):

Y. Yan ◽

W. Ma ◽

M. Molmen ◽

T. Regalo ◽

D. Pavlick ◽

...

Keyword(s):

Real World ◽

Circulating Tumor Dna ◽

Genomic Profiling ◽

Comprehensive Genomic Profiling ◽

Tumor Dna

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Complementary detection of genomic alterations in metastatic castration-resistant prostate cancer (mCRPC) from CheckMate 9KD through analyses of tumor tissue and plasma DNA.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.5038 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 5038-5038

Author(s):

Mark Sausen ◽

Jonathan F. Baden ◽

Natallia Kalinava ◽

Xuya Wang ◽

Jun Li ◽

...

Keyword(s):

Circulating Tumor Dna ◽

Genomic Alteration ◽

Castration Resistant Prostate Cancer ◽

Plasma Dna ◽

Accurate Analysis ◽

Specific Patient ◽

Formalin Fixed Paraffin Embedded ◽

Comprehensive Genomic Profiling ◽

Tissue Specimens ◽

Tumor Dna

5038 Background: Accurate analysis of the genomic alteration landscape within tissue- and plasma-derived tumor DNA using next-generation sequencing (NGS) may provide insights into specific patient populations that benefit from different therapies. The interchangeable use of tissue- and plasma-based assessments may benefit patients when tissue availability is limited, a common occurrence in individuals with mCRPC. To understand the potential sources of technical and biological variability in this setting, we performed comprehensive comparative analyses across 3 NGS platforms, using samples from patients enrolled in CheckMate 9KD, a phase 2 study of nivolumab combined with docetaxel, rucaparib, or enzalutamide for patients with confirmed mCRPC (NCT03338790). Methods: We performed retrospective integrated analyses of sequence and structural alterations identified through comprehensive genomic profiling (CGP) of DNA obtained from formalin-fixed, paraffin-embedded tissue specimens and cell-free DNA obtained from plasma. Tissue-based analysis was performed using the FoundationOne assay (F1, 395 genes), while the FoundationACT (FACT, 70 genes) and GuardantOMNI (OMNI, 500 genes) assays were used for plasma-based analysis. Analysis was performed on samples from 103 patients for which datasets from all 3 assays were available. Inter-platform analysis considered variants with ≥ 0.50% variant allele fraction and common to the shared pairwise targeted regions, while excluding synonymous variants. Results: Through broad profiling of DNA obtained from tissue and plasma, we uncovered previously identified recurrent alteration of AR, TP53, PTEN, and TMPRSS2 fusion with ETS genes. Additionally, we found that 42% (F1), 45% (FACT), and 34% (OMNI) of patients harbored a combination of germline and somatic mutations in homologous recombination repair pathway genes. Across all samples, median tumor mutational burden was 3.5 mutations per megabase (mut/Mb) by F1 and 8.6 mut/Mb by OMNI. Inter-platform variant analyses demonstrated concordance of 52% for F1 vs FACT, 40% for F1 vs OMNI, and 75% for FACT vs OMNI. Conclusions: Overall, these data demonstrate the value of integrated tissue and liquid biopsy profiling in mCRPC. Both technical and biological sources of variation, including panel size, mutation detection algorithms, variant annotation and reporting, analytical performance, circulating tumor DNA levels, and tumor heterogeneity, may be captured differently by tissue- and plasma-based techniques, accounting for the discordance in reported results. Clinical trial information: NCT03338790.

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Association of detectable levels of circulating tumor DNA (ctDNA) with disease burden in prostate cancer (PC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.5562 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 5562-5562 ◽

Cited By ~ 1

Author(s):

Gerhardt Attard ◽

Michael Gormley ◽

Karen Urtishak ◽

Jason S. Simon ◽

Deborah S. Ricci ◽

...

Keyword(s):

Clinical Outcome ◽

Disease Burden ◽

Cox Regression ◽

Specific Antigen ◽

Point Mutations ◽

Progression Free Survival ◽

Circulating Tumor Dna ◽

Response To Therapy ◽

Bone Lesions ◽

Copy Number Changes

5562 Background: PC is characterized by a relatively low prevalence of recurrent somatic point mutations. ctDNA is shed from PC and can be analyzed to profile somatic point mutations and copy number changes. We evaluated a computational approach to detect ctDNA (ie. ctDNA+) in PC based on allele frequencies of polymorphisms and mutations. We then sought to confirm the association of this biomarker with disease burden and clinical outcome. Methods: Customized, hybrid capture, high-depth next-generation sequencing was performed on pre-treatment (PT) plasma samples from a phase 2 line 3+ metastatic castration-resistant PC (mCRPC) study (NCT02854436, GALAHAD) and PT and end of treatment (EOT) samples from randomized Phase 3 study in non-metastatic (nm) CRPC (NCT01946204, SPARTAN) and from metastatic castration-sensitive PC (mCSPC) (NCT02489318, TITAN). Associations of ctDNA+ with bone lesions (number), visceral metastases (+/-), circulating tumor cells count (CTCc), and serum prostate specific antigen (PSA), alkaline phosphatase (AP) and lactate dehydrogenase (LD) were tested. Also, associations of ctDNA+ with overall survival (OS) and second progression free survival (PFS2) were evaluated in randomized studies using Cox regression. Results: ctDNA+ at PT was 7.5% in nmCRPC, 23.7% in mCSPC and 66% in heavily pre-treated mCRPC. ctDNA+ increased from PT to EOT in nmCRPC (7.5% to 27%) and mCSPC (23.7% to 63.6%). Disease burden metrics were evaluated in ctDNA+ vs ctDNA- patients. ctDNA+ was associated with higher disease burden in mCRPC (Table), nmCRPC and mCSPC. At EOT, ctDNA+ patients had shorter OS and PFS2 in nmCRPC (HR [95% CI] OS: 2.73 [1.83, 4.08], p < 0.0001; PFS2: 2.00 [1.38, 2.90], p = 0.0002) and mCSPC (HR [95% CI] OS: 7.59 [3.22, 17.91], p < 0.0001; PFS2: 4.84 [2.47, 9.47], p < 0.0001). Conclusions: ctDNA+ assessed using our novel, composite biomarker increases with advanced disease state and disease progression, is significantly associated with disease burden and poor clinical outcome in PC and could be a clinically relevant metric for monitoring response to therapy. Clinical trial information: NCT02854436 . [Table: see text]

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The effect of treatment sequence on overall survival for men with metastatic castration-resistant prostate cancer: A multicenter retrospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.238 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 238-238

Author(s):

Shingo Hatakeyama ◽

Kazutaka Okita ◽

Hayato Yamamoto ◽

Takahiro Yoneyama ◽

Yasuhiro Hashimoto ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Real World ◽

Cox Regression ◽

Sequential Therapy ◽

Treatment Sequence ◽

Castration Resistant Prostate Cancer ◽

First Line ◽

Castration Resistant ◽

Significant Difference

238 Background: We aimed to evaluate the treatment sequence for patients with metastatic castration-resistant prostate cancer (mCRPC) in real-world practice and compare overall survival in each sequential therapy. Methods: We retrospectively evaluated 146 patients with mCRPC who were initially treated with androgen deprivation therapy as metastatic hormone-naïve prostate cancer in 14 hospitals between January 2010 and March 2019. The agents for the sequential therapy included new androgen receptor-targeted agents (ART: abiraterone acetate or enzalutamide), docetaxel, and/or cabazitaxel. We evaluated the treatment sequence for mCRPC and the effect of sequence patterns on overall survival. Results: The median age was 71 years. A total of 35 patients received ART-ART, 33 received ART-docetaxel, 68 received docetaxel-ART, and 10 received docetaxel-cabazitaxel sequences. The most prescribed treatment sequence was docetaxel-ART (47%), followed by ART-ART (24%). Overall survival calculated from the initial diagnosis reached 83, 57, 79, 37 months in the ART-ART, ART-docetaxel, docetaxel-ART, and docetaxel-cabazitaxel, respectively. Multivariate Cox regression analyses showed no significant difference in overall survival between the first-line ART (n = 68) and first-line docetaxel (n = 78) therapies (hazard ratio: HR 0.84, P = 0.530), between the ART-ART (n = 35) and docetaxel-mixed (n = 111) sequences (HR 0.82, P = 0.650), and between the first-line abiraterone (n = 32) and first-line enzalutamide (n = 36) sequences (HR 1.58, P = 0.384). Conclusions: The most prescribed treatment sequence was docetaxel followed by ART. No significant difference was observed in overall survival among the treatment sequences in real-world practice.

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Evaluation of PSA progression after initiation of enzalutamide or abiraterone: Real-world data on metastatic castration-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.5024 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 5024-5024

Author(s):

Fernando López-Campos ◽

David Lorente ◽

Casilda Llacer Perez ◽

Miguel Ramirez-Backhaus ◽

Paula Peleteiro ◽

...

Keyword(s):

Real World ◽

Cox Regression ◽

Castration Resistant Prostate Cancer ◽

Real World Data ◽

Castration Resistant ◽

Real World Setting ◽

Psa Progression ◽

Definition Of ◽

The Impact

5024 Background: PSA value is widely used for the monitoring of treatment outcome in mCRPC in the clinical real-world setting. Early PSA changes are not considered in the definition of PSAProg due to the potential for spurious “flare” reactions. We aimed to evaluate the significance of an early PSA increase in mCRPC patients (pts) treated with enzalutamide or abiraterone (Enz/Abi). Methods: We retrospectively evaluated Enz/Abi-treated mCRPC pts from 11 hospitals between 2011-2020. Early PSAProg was defined as a 25% increase in PSA from baseline at 4 (PSAProg4) or 8 (PSAProg8) weeks after treatment initiation. PSA progression at 12 weeks (PSAProg12) was confirmed by a second reading. Uni- and multivariable (MV) Cox regression models were conducted to explore the association of PSAProg and overall survival (OS) in chemotherapy naïve patients treated with Abi or Enz. Interaction tests were conducted to explore differences in the impact of PSA progression on OS in Abi or Enz-treated pts. Results: We analyzed 511 chemotherapy-naïve mCRPC pts treated with Abi (N=391; 76.5%) or Enz (N=120; 23.5%). Median follow-up: 30.2 months. OS was longer in Enz-treated pts (38.1 vs 29m; HR 1.4; p=0.027). 59 (15.1%), 70 (17.9%) and 48 (12.3%) of Abi-treated and 9 (7.5%), 11 (9.2%) and 10 (8.3%) of Enz-treated pts experienced PSAProg4, PSAProg8 and PSAProg12, respectively, although differences were not statistically significant. PSAProg was associated with worse OS at all 3 timepoints only in Abi-treated pts. In Enz-treated pts, PSAProg4 had a large impact on OS, not observed in PSAProg8 or PSAProg12. We observed no significant interaction between agent (Enz/Abi) and PSA progression (Table). Conclusions: PSA progression at 4 weeks after Enz/Abi is significantly associated with shorter OS and may help identify pts not benefitting from Abi/Enz before clinical or radiographic progression. PSA pattern progression and its association with OS might differ depending on the drug used (Enz/Abi). Prospective validation studies are needed.[Table: see text]

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Real-world treatment attrition rates in advanced esophagogastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e19301 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e19301-e19301

Author(s):

Erica S Tsang ◽

Howard John Lim ◽

Daniel John Renouf ◽

Janine Marie Davies ◽

Jonathan M. Loree ◽

...

Keyword(s):

Real World ◽

Cox Regression ◽

De Novo ◽

Unmet Need ◽

Treatment Attrition ◽

Her2 Positive ◽

Real World Data ◽

Attrition Rates ◽

Esophagogastric Cancer ◽

Line Of Therapy

e19301 Background: Over the last decade, multiple agents have demonstrated efficacy for advanced esophagogastric cancer (EGC). Despite the availability of later lines of therapy, there remains limited real-world data about the treatment attrition rates between lines of therapy. We sought to characterize the use and attrition rates between lines of therapy for patients with advanced EGC. Methods: We identified patients who received at least one cycle of chemotherapy for advanced EGC between July 1, 2017 and July 31, 2018 across 6 regional centers in British Columbia (BC), Canada. Clinicopathologic, treatment, and outcomes data were extracted by chart review. Patients who continued on treatment were censored at the date of last contact. Results: Of 245 patients who received at least one line of therapy, median age was 65.7 years (IQR 58.2-72.3) and 186 (76%) were male, ECOG PS 0/1 (80%), gastric vs. GEJ (36% vs. 64%). Histologies included adenocarcinoma (78%), squamous cell carcinoma (8%), and signet ring (14%), with 31% HER2 positive. 72% presented with de novo disease, and 25% had received previous chemoradiation. There was a high level of treatment attrition, with patients receiving only one line of therapy (n = 122, 50%), two lines (n = 83, 34%), three lines (n = 34, 14%), and four lines (n = 6, 2%). Kaplan-Meier survival analysis demonstrated improved survival with increasing lines of therapy (median overall survival 7.7 vs. 16.6 vs. 22.8 vs. 40.4 months, p< 0.05). On multivariable Cox regression, improved survival was associated with better baseline ECOG and increased lines of therapy ( p< 0.05). Conclusions: The steep attrition rates between therapies highlight the unmet need for more efficacious earlier-line treatment options for patients with advanced EGC. [Table: see text]

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Real-world treatment attrition rates in advanced esophagogastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.317 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 317-317

Author(s):

Erica S. Tsang ◽

Howard John Lim ◽

Daniel John Renouf ◽

Janine Marie Davies ◽

Jonathan M. Loree ◽

...

Keyword(s):

Real World ◽

Cox Regression ◽

De Novo ◽

Unmet Need ◽

Treatment Attrition ◽

Her2 Positive ◽

Real World Data ◽

Attrition Rates ◽

Esophagogastric Cancer ◽

Line Of Therapy

317 Background: Over the last decade, multiple agents have demonstrated efficacy for advanced esophagogastric cancer (EGC), including ramucirumab, irinotecan, trifluridine/tipiracil, and immunotherapy. Despite the availability of later lines of therapy, there remains limited real-world data about the treatment attrition rates between lines of therapy. We sought to characterize the use and attrition rates between lines of therapy for patients with advanced EGC. Methods: We identified patients who received at least one cycle of chemotherapy for advanced EGC between July 1, 2017 and July 31, 2018 across 6 regional centers in British Columbia (BC), Canada. Clinicopathologic, treatment, and outcomes data were extracted by chart review. Results: Of 169 patients who received at least one line of therapy, median age was 65.2 years (IQR 58-72) and 128 (76%) were male, ECOG PS 0/1 (84%), gastric vs GEJ (35% vs 65%). Histologies included adenocarcinoma (76%), squamous cell carcinoma (10%) and signet ring (14%), with 26% HER2 positive. 62% presented with de novo disease, and 35% had received previous chemoradiation. There was a high level of treatment attrition, with patients receiving only one line of therapy (n = 73, 43%), two lines (n = 65, 38%), three lines (n = 25, 15%), and four lines (n = 6, 4%). Kaplan-Meier survival analysis demonstrated improved survival with increasing lines of therapy (median overall survival 9.6 vs. 18.5 vs. 25.8 vs. 40.7 months, p< 0.05). On multivariable Cox regression, improved survival was associated with better baseline ECOG, longer duration of first-line therapy, and increased lines of therapy ( p< 0.01). Conclusions: The steep attrition rates between therapies highlight the unmet need for more efficacious earlier-line treatment options for patients with advanced EGC. [Table: see text]

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Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽

10.3390/cancers13102489 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2489

Author(s):

Sazan Rasul ◽

Tim Wollenweber ◽

Lucia Zisser ◽

Elisabeth Kretschmer-Chott ◽

Bernhard Grubmüller ◽

...

Keyword(s):

Response Rate ◽

Cox Regression ◽

Progression Free Survival ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Free Survival ◽

Castration Resistant ◽

Kaplan Meier ◽

Node Metastases ◽

Grade 3

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

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