Similarly, a study on the toxicity of the re-challenged patient cohort with 177Lu-PMSA-617 reported no unexpected adverse events with 177Lu-PSMA-617 retreatment [4]. Twenty-seven patients with disease progression further underwent other lines of treatment, among which 16 patients primarily received 225Ac-PSMA-617 therapy and have shown remarkable response rate. Methodology, All Rights Reserved. Click through the PLOS taxonomy to find articles in your field. In the early stages of cancer, these methods might give long-term remission but in advanced metastatic prostate cancer, they only help in shrinking the tumors instead of curing the disease. Moreover, it is also essential to know the treatment paradigm after progressing on 177Lu-PSMA-617 therapy. The estimated median PFS and OS were 12 months (mo) (95% CI: 10.313 mo) and 16 mo (95% CI: 1317 mo), respectively. Thirty-three patients demonstrated molecular disease progression at their first interim 68Ga-PSMA PET/CT scan and did not respond to further treatment (Table 5). In the future, even administering concurrent therapies in these patients is feasible.

Project administration, 177Lu-PSMA-617 prolongs the overall survival in mCRPC patients heavily pre-treated with chemotherapy, first and second-line anti-androgens, and androgen inhibitor therapies. PSMA therapywith Lutetium 177 in specialized hospitals ranges between 8000- 16,000 euros. information submitted for this request. Writing original draft, Interestingly, the multivariate analysis also revealed that patients who were further treated after 177Lu-PSMA-617 therapy with second-line and salvage treatment options showed a significantly prolonged survival with the least hazards ratio of 0.3; 95% CI: 0.164 0.550; P-0.0001 (Fig 3E) (Table 3). Project administration, health information, we will treat all of that information as protected health The primary outcome measure included overall survival. (Table 2) (Fig 3A). Supervision, Hence the treatment protocol was individualized and may suffer from heterogeneity in the treatment and outcomes. Department of Medical Oncology, IRCH, AIIMS, Ansari Nagar, New Delhi, India, Roles Secondary outcome measures involved progression-free survival, factors predicting the OS and PFS, evaluation of the PSA response rate, molecular response assessment, clinical response assessment, and adverse event profile. Writing original draft,

We do not capture any email address. To provide you with the most relevant and helpful information, and understand which [4] and ours would be the second to elaborate the long-term outcome of patients treated with 177Lu-PSMA-617 RLT with a median follow-up duration of 36 months. Writing review & editing, Affiliation During the treatment and follow-up, 88 (73%) patients experienced any PSA decline, and the best PSA response of >50% PSA decline was seen in 74 (61%) patients. While, multivariate analysis revealed only failure to experience >50% PSA decline [HR: 2.5; 95% CI: 1.6973.939; P<0.0001] (Fig 3C), heavily pre-treated patients with >2 lines of prior standard treatment options [HR: 2.9; 95% CI: 1.2077.012; P-0.01] and patients who received more than one-line of chemotherapy [HR: 1.5; 95% CI: 1.0182.321; P-0.041] were remarkably associated with poor OS (Fig 3D). The median duration of first-line and second-line treatment has been detailed in Table 1. https://doi.org/10.1371/journal.pone.0251375.t001. Interim and the follow-up molecular response assessment could be assessed in 105 patients. On a detailed analysis of the various regimes of treatment that were opted in patients after either on progression during 177Lu-PSMA-617 therapy or during the follow-up period after completion of 177Lu-PSMA-617 therapy cycles, 27 patients underwent further salvage treatment options that are detailed in Table 4. The molecular response was assessed using PERCIST 1 criteria [8]. e0251375. The univariate analysis revealed no prior history of androgen-inhibitor treatment chemotherapy nave, patients experiencing any PSA decline and/or >50% PSA decline as significant predictors of prolonged PFS (Table 2).

Sign In to Email Alerts with your Email Address. information is beneficial, we may combine your email and website usage information with Only Two patients had only massive lymph node metastases. Prognostic factors associated with reduced OS included, failure to experience >50% PSA decline, heavily pre-treated patient cohort who received >2 lines of prior treatment options, and patient sub-group treated with 2 lines of chemotherapy. The pancytopenia was limited to grade 2, transient with a nadir around four weeks of therapy. The following therapy can take place in 6-8 weeks. Their median values designated the cut-offs for continuous variables. The following criteria are required to qualify for Lu-177 PSMA: If you have received treatment with Xofigo or other types of radiation therapy, for prostate cancer, you should wait 2 weeks after completion of these therapies before participating in lutetium-177 PSMA therapy. Conceptualization, Similarly, both the studies narrate the response and pattern of disease progression in patients during treatment and post-treatment follow-up. In addition to standard quality assessments, an evaluation of the size of lesions by Ga68 DOTANOC positron emission tomography/computed tomography scanning is performed at each three months interval after the last administration of the radioisotope. Paired-samples t-test (parametric) or Wilcoxon signed-rank test (non-parametric) tests were used to compare the pre and post-therapy parameters.

Thus, the initial 26 patients had a dose-escalation study for dosimetry purposes. Prospective RCTs comparing 177Lu-PSMA-617 with Olaparib (PARP inhibitor, recently FDA approved) and immunotherapy (PD-1 and PD-L1 inhibitors), respectively, are in the pipeline (NCT03874884) and (NCT03658447). Supervision,

The association of PSA response with the overall survival has been previous studied with variable results. The long-term follow-up of these patients after the completion of 177Lu-PSMA-617 RLT will best answer the delayed complications. However, scarce literature is reported on the long-term outcome of these patients. Investigation, All variables with P value 0.1 on univariate analysis Cox proportional-hazards regression model were included in the multivariate model. Afterward, the patient will move onto another exam table where they will remain for about 1 hour. Furthermore, 21 (17%) patients received more than four cycles.

The remaining 9% had at least two treatment lines before RLT; 83.4% of patients had received docetaxel, 53.7% (65/121) had androgen synthesis inhibitor therapy, and 19% (23/121) received enzalutamide. As a prerequisite, all patients underwent a pre-therapy diagnostic 68Ga-PSMA-11 PET/CT scans using 68Ga-PSMA-HBED-CC to ensure the presence of PSMA overexpression in a majority of the lesions. Combination therapy, especially regarding second-line androgen deprivation therapy or chemotherapy, was assessed in our patient population, and its use did not affect the OS in the long-run.

No hematological toxicity more than grade 1 was observed in the first four weeks. Investigation, [4]. include protected health information. The effectiveness of therapy is measured by performing the below investigations: After completing the scheduled number of administrations of the labeled peptide, measurements are taken to determine whether there was any change in the PSA level. Writing review & editing, Roles Sign up for free, and stay up to date on research advancements, health tips and current health topics, like COVID-19, plus expertise on managing health. This study identifies the prognostic factors associated with PFS and OS, gives an overview of the real-world clinical scenario of these patients after 177Lu-PSMA-617 therapy, the patterns of response, alternative subsequent anti-cancer systemic treatments following 177Lu-PSMA-617 therapy, and validate the findings with the short-term reports. Once the radiolabeled compound reaches the tumor site, it binds to receptors on the surface of cancerous cells. In a median time interval of 8 wks (range, 612 wks) between each 177Lu-PSMA-617 RLT treatment cycle, a total of 386 cycles were administered in 121 mCRPC patients. You are suffering from advanced metastatic castration-resistant prostate cancer, You are not responding to other treatments (i.e. A recently published meta-analysis in 744 mCRPC patients on 177Lu-PSMA-617 reported a pooled >50% PSA decline rate of 46% (95% CI, 4053%) [1]. Methodology, The delayed toxicity is low and acceptable by most of these patients. A patient may be recommended to have three treatments, but a single treatment may be enough. It emits high-energy gamma rays that can damage DNA inside the cancer cells. [4] reported a >50% PSA decline rate of 64% when re-treated with 177Lu-PSMA-617 RLT, which is well in line with the PSA response rate observed in the current study in 61% of patients. It may take multiple administrations of the radiolabeled agent to achieve maximum results. All the studies conducted to date have focused on short-term preliminary results including safety and efficacy data with limited long-term follow-up data [4]. Yes https://doi.org/10.1371/journal.pone.0251375.t003. Fifty-six percent of the patients are alive and have shown improved overall survival. Yes In agreement, meta-analysis data pooled from the previously published works addressed a median overall survival of 13.7 (IQR: 814) mo [1]. If your doctor suspects a problem, they will order blood tests to check levels of calcium, creatinine, liver function, etc. Your information is confidential. privacy practices. No, Is the Subject Area "Oncology" applicable to this article? Blood pressure is checked.

Hence, in the remaining 95 patients, only 177Lu-PSMA-617 was diluted in 30 mL normal saline (0.9%), and administered by slow intravenous infusion over 510 minutes. [13] and Ahmadzadehfar et al. The lutetium-177 PSMA is administered intravenously through a catheter. All rights reserved. The most common side effect from 177Lu-PSMA-617 treatment was grade I/II fatigue (42/121 [34.7%]) that lasted up to 2 wks post-RLT and nausea (40/121 [33%]) persisted for 34 days post-RLT. To the best of our knowledge, there is only one study by Violet et al. Three patients achieved complete response during the treatment and remained disease-free till their end-follow-up. hormonal therapy and chemotherapy), Full body scintigraphy before discharge from the hospital, Imaging studies PSMA PET CT scan, CT scan, Bone Scan 3-12 months post-treatment. Investigation, You may report side effects to the FDA at 1-800-FDA-1088. In this context, a pilot phase II study from the Australian New Zealand trial group has reported long-term outcomes of retreatment with 177Lu-PSMA-617 in an expanded cohort of 50 mCRPC patients which includes 30 patients who were previously enrolled in the phase II trial.

Any use of this site constitutes your agreement to the Terms and Conditions and Privacy Policy linked below. P-values <0.05 were considered significant. The current study supports the short-term safety and efficacy results of high response rates, prolonged PFS and OS, improved quality of life, and low treatment-related toxicities in patients treated with 177Lu-PSMA-617 radioligand therapy. [17] observed second-line cabazitaxel chemotherapy (6.7 vs. 15.7 mo, P = 0.002) significantly associated with a shorter OS compared to patients who had not received second-line chemotherapy (7.9 vs.14.6 mo, Log-rank P = 0.002; HR 2.1, P = 0.009). Any PSA decline and PSA decline >50% was achieved in 73% and 61% of the patients, respectively. Copyright 2022 | Booking Med Travel. Although not all of these side effects may occur, if they do occur they may need medical attention. Radioligand therapy (RLT) with 177Lu-PSMA-617 is a promising option in treating metastatic castration-resistant prostate cancer (mCRPC). Enter multiple addresses on separate lines or separate them with commas. An aggressive treatment approach, either sequential or in combination with second-generation anti-androgens, chemotherapies, or with investigational 225Ac-PSMA-617 alpha therapies, might prolong the survival of mCRPC patients in the future. Copyright: 2021 Yadav et al. However, some patients may require an additional cycle of treatments. Radioligand therapy using 177Lu-PSMA-617 has improved the overall survival (OS) and progression-free survival (PFS) in heavily pre-treated mCRPC patients. Following promising clinical and biochemical responses from the phase II results on 177Lu-PSMA-617 RLT, a randomized phase III study, the VISION trial (ClinicalTrials.gov, NCT03511664) is underway in mCRPC patients. broad scope, and wide readership a perfect fit for your research every time. Results 7 patients showed in Ga-PSMA-PET bone and lymph node metastases,of whom four patients also had residual/locally recurrent tumor. During the follow-up, 79 (65%) patients experienced disease progression with a median PFS of 12 mo (95% CI: 10.313), and a 24-months progression-free survival probability of 19.7% (Fig 2A). Compared to other forms of treatment like chemotherapy and external beam radiation, Lu-177 PSMA has several advantages: While there are many benefits to using Lu-177 PSMA over existing therapies, there are also potential drawbacks. [4] and further favours the concept of re-challenging patients with other advanced salvage treatment options after acquiring radio-resistance on 177Lu-PSMA-617 RLT. Investigation, Department of Urology, AIIMS, Ansari Nagar, New Delhi, India, Roles An ECG (Electrocardiogram) is done to determine heart rhythm. This allows the Lu-177 PSMA to damage the cell by delivering its payload of radiation directly to the cancerous cells. Wallis, University of Toronto, CANADA, Received: December 9, 2020; Accepted: April 23, 2021; Published: May 10, 2021. Violet et al. But it is recommended that patients drink plenty of fluids for several days before receiving the treatment.

Once the Lu-177 PSMA molecule enters the body, it travels throughout the bloodstream until it finds an area with active prostate cancer growth where it gets attached to the PSMA receptor.

No, Is the Subject Area "Prostate cancer" applicable to this article? There are no severe side effects associated with this form of treatment. Salivary glands were protected with ice packs during therapy. In 2014, we started the 177Lu-PSMA-617 RLT when there were no dosimetry reports available for the dose-limiting organs. The median KPS and ECOG status significantly improved from 60 to 70 (P < 0.0001) and 3 to 2 (P = 0.0005), respectively. Supervision, This site complies with the HONcode standard for trustworthy health information: verify here. Treatment was ceased in the following circumstances: Progression of disease, an early response to treatment which was attained before completion of the treatment regimen, no improvement in the quality of life with no clinical benefit after board discussion with the treating medical oncologist, achieved the maximum administered activity dose limit of ~37 GBq (1000 mCi). Formal analysis, The baseline characteristics of patients are displayed in Table 1. One of the key findings from this study indicates that the overall survival remarkably improved in the patient cohort who were eventually treated with other anti-cancer treatment options after the discontinuation of 177Lu-PSMA-617 RLT. The multicentre analysis revealed prior chemotherapy as a significant independent adverse prognostic factor for poor overall survival. This type of therapy is referred to as radiopharmaceutical therapy (RPT) and involves using a radioactive substance that targets specific molecules on the surface of cancer receptors. This study aimed to give an overview on the long-term outcome of 177Lu-PSMA-617 therapy in a heavily pre-treated mCRPC patient cohort, who had received at least two lines of prior treatment; particularly, focused on the survival outcomes and the prognostic factors that influence the survival. Despite the encouraging results, the long-term data is crucial to decide if 177Lu-PSMA-617 RLT therapy has a sustained response rate. Objectives Peptide radionuclide ligand therapy (PRLT) with 177Lu-PSMA-DKFZ 617 (LU-PSMA) (prostate-specific membrane antigen)is a novel targeted therapy of metastatic prostate cancer.We present the first clinical experiences assessing early possible side effects of this therapy. We observed that a PSA response of >50% is a significant predictor of prolonged OS. Patients who were treated with various other mCRPC-approved compounds before 177Lu-PSMA-RLT were associated with a significantly shorter OS than that of the patients who received 177Lu-PSMA RLT at the earlier stages of mCRPC. Methods PRLT was performed in nine hormone and/or chemo refractory patients with distant metastases and progressive disease (mean age: 72 y/o).68Ga-PSMA PET/CT was performed in all patients 1-2 weeks prior to PRLT. These side effects may go away during treatment as your body adjusts to the medicine. From this long-term follow-up study, we conclude that 177Lu-PSMA-617 RLT is an effective form of therapy in mCRPC patients and confirms the findings of the short-term studies. During the visit, you will be asked for a complete medical history, including all medications taken, current medication, allergies (if any), and family medical history. No, PLOS is a nonprofit 501(c)(3) corporation, #C2354500, based in San Francisco, California, US, Corrections, Expressions of Concern, and Retractions, https://doi.org/10.1371/journal.pone.0251375, https://doi.org/10.1016/s1470-2045(18)30198-0, https://doi.org/10.2967/jnumed.119.236414, https://doi.org/10.1097/rlu.0000000000002833, https://doi.org/10.1097/mnm.0000000000000606, https://doi.org/10.1046/j.1365-2702.2000.0374c.x, https://doi.org/10.18632/oncotarget.21600, https://doi.org/10.1007/s00259-017-3751-z, https://doi.org/10.1007/s00259-017-3716-2, https://doi.org/10.1007/s00259-017-3848-4, https://doi.org/10.1016/j.eururo.2018.11.016, https://doi.org/10.1007/s00259-020-04797-9. After the administration of 177Lu-PSMA-617, all patients were admitted to the isolation therapy ward for clinical observation and eventually discharged when stable [5]. https://doi.org/10.1371/journal.pone.0251375.t004. Yes The long-term PSA response rates concur well with both previously published retrospective and prospective short-term results [1]. Writing review & editing. Copyright 2022 IBM Watson Health. Yes In this study, we present a single institutional 6-year experience by highlighting the long-term outcome of 177Lu-PSMA-617 therapy. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. Resources, [18], both univariate and multivariate analyses demonstrated prior treatment with >2 lines of therapies, and a prior history of 2 lines of chemotherapy significantly reduced OS. The secondary objective of our study was to identify the prognostic factors influencing overall survival. In this context, Ahmadzadehfar et al. Prostate cancer is the second leading cause of cancer deaths in men.

Resources, Then medical personnel will inject the carrier containing the isotopes through a needle into the patient's arm. here. No, Is the Subject Area "Radiation therapy" applicable to this article? Formal analysis, Moreover, the long-term OS data were similar to and consistent with the short-term survival data. Along with its needed effects, a medicine may cause some unwanted effects. The median OS was 16 mo (95% CI: 1317 mo) irrespective of response to treatment with a 12 and 24-months survival probability of 77% and 18%, respectively (Fig 2B). Overall survival. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. The most awaited among the trials include the VISION phase III trial comparing 177Lu-PSMA-617 vs. best supportive or best standard of care in mCRPC patients (NCT03511664). This content does not have an English version. [18] retrospectively evaluated the impact of prior therapies on OS in 416 patients treated with 177Lu-PSMA-617 from 11 different clinics. Methodology, Similarly, a significant decrease in mean AS from the baseline was observed (3 vs. 2 1 [P< 0.000]). The impact of further treatment post after 177Lu-PSMA-617 may be the underlying fact for improved survival of 22 mo compared to 14 mo in the re-treatment nave cohort. Yes they were transient and limited to grade I/II only. PLOS ONE promises fair, rigorous peer review,

here. Funding acquisition, Project administration, No, Is the Subject Area "Chemotherapy" applicable to this article? Writing review & editing, Roles 1998-2022 Mayo Foundation for Medical Education and Research (MFMER). Your doctor decides that the benefits outweigh the risks associated with the procedure. There was a significant reduction in the VASmax score post-treatment (8 vs. 5; P < 0.0001). However, a later study by Ahmadzadehfar et al. Among them, 38 patients had shown >50% PSA response during some point of the treatment and follow-up.

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