scholarly journals Durvalumab after Chemoradiotherapy for PD-L1 Expressing Inoperable Stage III NSCLC Leads to Significant Improvement of Local-Regional Control and Overall Survival in the Real-World Setting

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1613
Author(s):  
Julian Taugner ◽  
Lukas Käsmann ◽  
Chukwuka Eze ◽  
Amanda Tufman ◽  
Niels Reinmuth ◽  
...  
Keyword(s):  
Overall Survival ◽  
Real World ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Historical Cohort ◽  
Free Survival ◽  
Stage Iii Nsclc ◽  
Local Regional Control ◽  
Nsclc Patients

Concurrent chemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is a new standard of care for inoperable stage III NSCLC. The present study compares the oncological outcome of patients treated with CRT to those treated with CRT and durvalumab (CRT-IO) in the real-world setting. The analysis was performed based on the retro- and prospectively collected data of 144 consecutive inoperable stage III NSCLC patients treated between 2011–2020. Local-regional-progression-free-survival (LRPFS—defined as progression in the mediastinum, hilum and/or supraclavicular region at both sites and the involved lung), progression-free survival (PFS), and overall survival (OS) were evaluated from the last day of thoracic radiotherapy (TRT). Median follow-up for the entire cohort was 33.1 months (range: 6.3–111.8) and median overall survival was 27.2 (95% CI: 19.5–34.9) months. In the CRT-IO cohort after a median follow-up of 20.9 (range: 6.3–27.4) months, median PFS was not reached, LRPFS (p = 0.002), PFS (p = 0.018), and OS (p = 0.005) were significantly improved vs. the historical cohort of conventional CRT patients. After propensity-score matching (PSM) analysis with age, gender, histology, tumor volume, and treatment mode, and exact matching for T-and N-stage, 22 CRT-IO patients were matched 1:2 to 44 CRT patients. Twelve-month LRPFS, PFS, and OS rates in the CRT-IO vs. CRT cohort were 78.9 vs. 45.5% (p = 0.002), 60.0 vs. 31.8% (p = 0.007), and 100 vs. 70.5% (p = 0.003), respectively. This real-world analysis demonstrated that durvalumab after CRT led to significant improvement of local-regional control, PFS, and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort.

279 Durvalumab after chemoradiotherapy for PD-L1 expressing inoperable stage III NSCLC impacts local-regional control and overall survival

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A304-A304
Author(s):  
Lukas Kaesmann ◽  
Julian Taugner ◽  
Chukwuka Eze ◽  
Claus Belka ◽  
Farkhad Manapov
Keyword(s):  
Overall Survival ◽  
Real World ◽  
Stage Iii ◽  
Historical Cohort ◽  
Free Survival ◽  
Regional Control ◽  
Stage Iii Nsclc ◽  
Local Regional Control ◽  
Nsclc Patients

BackgroundChemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is a new standard of care for inoperable stage III NSCLC. The present study aims to evaluate the oncological outcome of patients treated with CRT alone to those treated with CRT and durvalumab (CRT-IO) in the real-world setting.MethodsRetro- and prospectively collected data of 133 consecutive inoperable stage III NSCLC patients treated between 2011–2019 were evaluated. Local-regional-recurrence-free-survival (LRPFS - defined as progression in the mediastinum, hilum and/or supraclavicular region at both sides and the involved lung), progression-free survival (PFS) and overall survival (OS) were evaluated from last day of thoracic radiotherapy (TRT).ResultsMedian age at diagnosis was 68.5 years; 44 (33%) were female; 58 (44%) were diagnosed with adenocarcinoma. All patients were irradiated to a total dose of at least 60 Gy (EQD2). Median PTV was 709.8 cc (range: 181–1958 cc). 113 (85%) patients were treated with CRT and 20 (15%) PD-L1 expressing patients with CRT-IO. 83% of patients received two cycles of concomitant platinum-based chemotherapy. Median time to initiation of durvalumab after CRT was 0.8 months (range: 0.4–2.1). Median follow-up for entire cohort was 33.3 months (range: 4.8–111.8) and median overall survival (OS) was 24.7 (95% CI: 18.9–30.4) months. In the CRT-IO cohort after a median follow-up of 15.5 (range: 5.1–20.2) months, no deaths were reported at the time of evaluation (August 2020). Improved LRPFS (p=0.013), PFS (p=0.033) and OS (p=0.002) were correlated with CRT-IO compared to the historical cohort of conventional CRT patients.After propensity-score matching (PSM) analysis with age, gender, histology, tumor volume and treatment mode and exact matching for T-and N-stage, 18 CRT-IO patients were matched 1:2 to 36 CRT patients. 12-month LRPFS, PFS and OS rates in the CRT-IO vs CRT cohort were 80% vs 38.8% (p=0.001), 50% vs 22% (p=0.013) and 100% vs 75% (p=0.002), respectively. Also regarding intracranial failure, 6-month brain metastases rates were 0% vs. 6% in the CRT-IO vs CRT cohort (p=0.290).ConclusionsThis real-world analysis demonstrates that durvalumab after CRT has led to significant improvement of local-regional control, PFS and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort.AcknowledgementsThe study was partly presented at 2020 Annual Meeting of the American Society of Clinical Oncology (ASCO).Trial RegistrationN/AEthics ApprovalThe study was approved by Ludwig-Maximilians-University (LMU), Munich, Germany: Institution’s Ethics Board, approval number 17-230.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Association of planning target volume with disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20557-e20557
Author(s):  
Julian Taugner ◽  
Monika Karin ◽  
Lukas Käsmann ◽  
Chukwuka Eze ◽  
Julian Guggenberger ◽  
...  
Keyword(s):  
Planning Target Volume ◽  
Progression Free Survival ◽  
Target Volume ◽  
Continuous Variable ◽  
Stage Iii ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Free Survival ◽  
Stage Iii Nsclc ◽  
Nsclc Patients

e20557 Background: The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Methods: Prospective data of thirty-nine consecutive patients with inoperable stage III NSCLC who completed CRT with sequential durvalumab (72%, 28 patients) or concurrent and sequential nivolumab (28%, 11 patients) were analyzed. Different cut offs for PTV as well as PTV as a continuous variable were evaluated for association with progression-free survival (PFS) and extracranial metastasis-free survival (eMFS). Results: All patients were treated with conventionally fractionated TRT to a total dose of at least 60 Gy (range: 60-63.6Gy), 97% (27 patients) received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 23.2 (range: 6.0-42.6) months; median overall survival (OS) and eMFS were not reached. Median Progression-free survival (PFS) was 22.8 (95% CI: 10.3-35.2) months. Age (65 years), gender and UICC stage had no significant impact on PFS. There was no significant difference between durvalumab and nivolumab patients. Patients with PTV ≥ 900ccm had a significantly shorter PFS (11.77 vs 26.3 months, p = 0.049) and eMFS (11.7 months vs not reached, p = 0.019). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (TNM 8th Ed.) achieved a dismal median PFS of only 3.6 months (vs. 26.3 months p < 0.001). PTV as a continuous variable showed a trend for association with PFS (p = 0.064) and was a significant negative prognosticator for eMFS (p = 0.030; HR: 4.065; 95%CI: 1.148-14.397). Conclusions: PTV has a significant impact on the PFS and eMFS after CRT combined with concurrent and/or sequential CPI in inoperable stage III NSCLC. Patients with PTV ≥ 900ccm had a significantly shorter PFS and eMFS.

scholarly journals Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6193
Author(s):  
Jian-Yue Jin ◽  
Chen Hu ◽  
Ying Xiao ◽  
Hong Zhang ◽  
Rebecca Paulus ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Dose ◽  
Immune Cells ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Tumor Control ◽  
High Dose ◽  
Free Survival ◽  
Stage Iii Nsclc

Background: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: This is a secondary study of a phase III trial, NRG/RTOG 0617, in patients with stage III NSCLC treated with radiation-based treatment. The EDIC was computed as equivalent uniform dose to the entire blood based on radiation doses to all blood-containing organs, with consideration of blood flow and fractionation effect. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and local progression-free survival (LPFS). The EDIC–survival relationship was analyzed with consideration of clinical significant factors. Results: A total of 456 patients were eligible. The median EDIC values were 5.6 Gy (range, 2.1–12.2 Gy) and 6.3 Gy (2.1–11.6 Gy) for the low- and high-dose groups, respectively. The EDIC was significantly associated with OS (hazard ratio [HR] = 1.12, p = 0.005) and LPFS (HR = 1.09, p = 0.02) but PFS (HR = 1.05, p = 0.17) after adjustment for tumor dose, gross tumor volume and other factors. OS decreased with an increasing EDIC in a non-linear pattern: the two-year OS decreased first with a slope of 8%/Gy when the EDIC < 6 Gy, remained relatively unchanged when the EDIC was 6–8 Gy, and followed by a further reduction with a slope of 12%/Gy when the EDIC > 8 Gy. Conclusions: The EDIC is a significant independent risk factor for poor OS and LPFS in RTOG 0617 patients with stage III NSCLC, suggesting that radiation dose to circulating immune cells is critical for tumor control. Organ at risk for the immune system should be considered during RT plan.

Prognostic Relevance of Celiac Lymph Node Involvement in Ovarian Cancer

2014 ◽  
Vol 24 (1) ◽  
pp. 48-53 ◽  
Author(s):  
Alejandra Martínez ◽  
Cristophe Pomel ◽  
Thomas Filleron ◽  
Marjolein De Cuypere ◽  
Eliane Mery ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Oncologic Outcome ◽  
Progression Free Survival ◽  
Disease Spread ◽  
Short Term ◽  
Free Survival ◽  
Increased Risk

ObjectiveThe aim of the study was to report on the oncologic outcome of the disease spread to celiac lymph nodes (CLNs) in advanced-stage ovarian cancer patients.MethodsAll patients who had CLN resection as part of their cytoreductive surgery for epithelial ovarian, fallopian, or primary peritoneal cancer were identified. Patient demographic data with particular emphasis on operative records to detail the extent and distribution of the disease spread, lymphadenectomy procedures, pathologic data, and follow-up data were included.ResultsThe median follow-up was 26.3 months. The median overall survival values in the group with positive CLNs and in the group with negative CLNs were 26.9 months and 40.04 months, respectively. The median progression-free survival values in the group with metastatic CLNs and in the group with negative CLNs were 8.8 months and 20.24 months, respectively (P = 0.053). Positive CLNs were associated with progression during or within 6 months after the completion of chemotherapy (P = 0.0044). Tumor burden and extensive disease distribution were significantly associated with poor progression-free survival, short-term progression, and overall survival. In multivariate analysis, only the CLN status was independently associated with short-term progression.ConclusionsDisease in the CLN is a marker of disease severity, which is associated to a high-risk group of patients with presumed adverse tumor biology, increased risk of lymph node progression, and worst oncologic outcome.

scholarly journals Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Free Survival

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

Differential role of residual metabolic tumor volume in patients with inoperable stage III NSCLC after chemoradiotherapy ± immune checkpoint inhibition.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20558-e20558
Author(s):  
Marcus Unterrainer ◽  
Julian Taugner ◽  
Lukas Käsmann ◽  
Chukwuka Eze ◽  
Wolfgang G. Kunz ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Fdg Pet ◽  
Tumor Volume ◽  
Metabolic Tumor Volume ◽  
Stage Iii ◽  
Free Survival ◽  
Pet Ct ◽  
Stage Iii Nsclc ◽  
Fdg Pet Ct ◽  
Nsclc Patients

e20558 Background: PET-derived metabolic-tumor-volume (MTV) has shown to be an independent prognosticator in non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy (CRT). We analysed the prognostic value of residual MTV after completion of thoracic irradiation (TRT) in inoperable stage III NSCLC patients treated with CRT with and without immune check-point inhibition (ICI). Methods: Fifty-six inoperable stage III NSCLC patients (16 female, median age: 65 years) underwent 18F-FDG PET/CT at the same institution before and after completion of CRT. MTV was delineated on 18F-FDG PET/CT using a standard threshold (hepatic SUVmean + 2 x standard-deviation). Patients were divided in volumetric subgroups using median split dichotomization (residual MTV ≤4.0 ml & > 4.0 ml). Residual MTV, clinical features and ICI maintenance (RCT-IO; 21/56 (37.5%) patients) were correlated with clinical outcome (progression-free survival (PFS), local PFS (LPFS), metastasis-free survival (MFS), and overall survival (OS). Results: Median follow-up was 52.0 months. 52 (93%) patients were treated with CRT, 12 (21%) patients with CRT followed by durvalumab, and 9 (16%) patients treated with CRT plus nivolumab (concurrent and sequential). In the entire cohort, smaller residual MTV was associated with longer PFS (median 29.3 vs. 10.5 months, p = 0.015); PFS in patients treated with CRT and ICI was also significantly longer compared to the CRT-only subgroup (median 29.3 vs. 11.2 months, p = 0.010). However, residual MTV was predictive for longer PFS in CRT-only (median 33.5 vs. 8.6 months, p = 0.001), but not in the CRT-ICI patients (p = 0.909). Analogously, patients with smaller MTV had a longer LPFS (median 49.9 vs. 16.3 months, p = 0.002); CRT-ICI patients showed a significantly longer LPFS compared to CRT-only patients (median not reached vs. 16.9 months, p = 0.016). Residual MTV remained a significant prognosticator for LPFS in the CRT-only (median 49.9 vs. 10.1 months, p = 0.01), but not in CRT-ICI patients (p = 0.291). Again, smaller residual MTV remained a significant prognosticator for OS in the CRT-only subgroup (median 63.0 vs. 16.3 months, p = 0.004), but not in CRT-ICI patients (p = 0.720). Even in patients with larger residual MTV, the application of ICI significantly improved OS compared to CRT-only subgroup (median not reached vs. 22.9 months, p = 0.004). Conclusions: Smaller residual MTV is associated with superior clinical outcome in inoperable stage III NSCLC, especially in patients undergoing CRT-only. In contrast, in patients undergoing concurrent or sequential consolidation clinical outcome was independent of residual MTV. Hence, even patients with extensive residual MTV might significantly profit from ICI consolidation.

A prospective data analysis of targeted therapy combined with concurrent radiation therapy for brain metastasis from NSCLC with driver gene mutation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14006-e14006
Author(s):  
Xiaotong Duan ◽  
Xiaoxia Zhu ◽  
Lijuan Wang
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Gene Mutation ◽  
Progression Free Survival ◽  
Driver Gene ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Concurrent Radiotherapy ◽  
Nsclc Patients

e14006 Background: Previous studies have shown that brain metastases of non-small cell lung cancer (NSCLC) with positive driver genes have poor prognosis. There is still lack of prospective studies on the efficacy and safety of targeted therapy combined with concurrent radiotherapy for brain metastases(BM). Methods: NSCLC patients, with ECOG score 0-2, having MRI confirmed brain or meningeal metastases were eligible. Patients must have driver gene mutation and received corresponding targeted therapy. The intracranial radiotherapy regimen was SRS or whole brain radiotherapy. The primary objective was iPFS (intracranial progression-free survival); Secondary objectives were: iORR (intracranial objective response rate), PFS (progression-free survival), OS (overall survival). MMSE (Mini Mental State Examination) and FACT-Br was carried out before/after weekly radiotherapy and during systematic treatment. Treatment-related toxicities were assessed according RTOG/EORTC criteria. Tumor responses were evaluated using RECIST V1.1 criteria. Survival analysis was performed using the Graphprism version 6.0 by Kaplan-Meier method and log-rank test. Results: 23 NSCLC with BM was included. Among them, 10 patients were newly diagnosed with NSCLC BM. 2 patients’ BM progressed after targeted therapy. 11 NSCLC patients were newly diagnosed with BM after targeted therapy. 91.3% of patients presented an EGFR mutation, including primarily EGFR 19-exon deletion, EGFR 21-L8585R. 11.5% presented with c-MET mutation. Median age was 58.34 yrs(44-71yrs). Patients were mostly treated with Erolotinib and Gefitinib. All patients were adenocarcinoma. At last follow-up, for patients newly diagnosed with NSCLC BM, 8 patients had achieved intracranial progression, and 7 patients had reached OS, of which 1 died before completing WBRT. The median iPFS was 9.3m(95%CI:0.571-4.055) and the median OS was 11.9m (95%CI:0.2752 -2.732). As for patients who progressed after targeted therapy, one patient’s OS was 4.4m, iPFS of the other patient was 3.9m. Among NSCLC patients who were newly diagnosed with BM after targeted therapy, 8 patients had achieved intracranial progression and 5 patients had reached OS. The median iPFS was 6.13m (95%CI:0.247-1.751) and the mOS was 13.8m (95%CI:0.3660-3.634). Common adverse effects include dry skin, fatigue, dizziness, headache, anorexia, and grade I myelosuppression and no serious adverse events (SAEs); MMSE and FACT-Br scores were no significant differences at baseline and follow-up. Conclusions: In stage IV brain metastatic NSCLC with driver gene mutation, targeted therapy combined with concurrent radiotherapy for BM is tolerable, and there is no significant impact on the quality of life and cognitive function after radiotherapy. The evaluation of efficacy requires further follow-up. Support:LC2019ZD009,81972853 and 81572279.

Patterns of Care and Treatment Pathways for Non-Surgically Managed Early and Locally Advanced Non-Small Cell Lung Cancer Patients at Ain Shams University Clinical Oncology Department: a Retrospective and Descriptive Analysis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Dr/Khaled Abdel Karim ◽  
Dr/Khaled Nagib ◽  
Dr/Ahmed Hassan Abd El Aziz ◽  
Christina Gamil Garas
Keyword(s):  
Overall Survival ◽  
Clinical Oncology ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Patterns Of Care ◽  
P Value ◽  
Treatment Pathways ◽  
Free Survival ◽  
Care And Treatment ◽  
Nsclc Patients

Abstract Background Lung cancer is the leading cause of cancer death worldwide, but little is known about how patients with this disease are managed. Aim of the Work We aim to study patterns of care and treatment pathways of non- surgically managed early and locally advanced NSCLC patients from January 2015 to December 2018 in Ain Shams University Clinical Oncology Department. Patients and Methods In this retrospective analysis we included patients the met the following criteria; age &gt;18, histologically confirmed NSCLC patients whom didn’t undergo surgical resection with at least 6 months of follow up data. We collected data from Clinical Oncology department archive in Ain Shams university hospital. Our primary objective is to identify the patterns of care and treatment pathway for non surgically managed NSCLC patients in ASUCOD from January 2015 to December 2018. Results 86 patients finally met our inclusion criteria. Median age at diagnosis of 61 years with a range of (38-85), 95.3% were male. Most of the patients were stage III; 40.7% were stage IIIA, 41.9% were stage IIIB, and 9.3% were stage IIIC. 41 were treated radically, 37 received palliative treatment and only 8 patients received supportive care. Overall median progression free survival in our patients was 9.23 (7.4-13.5) and overall survival duration was13.4 (9.5-18.0). In radically treated patients, 68.3% received sequential chemoradiotherapy (sCRT), 29.2% received concurrent chemoradiotherapy (cCRT) or 2.4% received definitive radiotherapy alone (RT). In palliative treated patients, 73% received chemotherapy alone (CTX), 8.1% received palliative RT and 18.9% received both chemotherapy and palliative dose of radiotherapy (CRT). All treatment modalities were similar regarding median progression free survival and overall survival durations, 17.5 (3.6–19.6) and 20.6 (3.6–31.6) in cCRT, 17.5 (3.6–19.6) and 23.3 (17.7–31.2) in sCRT, 12.9 and 13.4 RT group, P value=0.57 and 0.16 receptively. Similarly, progression free survival and overall survival durations were 8.8 (3.0–15.8) and 16.2 (3.6–18.7) in CRT, 5.3 (0.4–7.6) and 8.6 (6.2–10.2) in CTX, 8.5 (0.4–8.5) and 8.5 (0.4–8.5) in palliative RT group, P value=0.64 and 0.15 receptively. In our study, first-line chemotherapy were Gemcitabine plus Cisplatin (41.9%) or Carboplatin (35.1%).The Second -line chemotherapy were Docetaxel (63.1%) or Paclitaxel plus Carboplatin (26.3%). Paclitaxel plus Carboplatin were the most regimen given with RT. Most of the patients received radiation dose of 60Gy/30Fr (73.2%). Regarding the incidence of toxicity, there were significant high rates of esophagitis in cCRT in grade 3 or more compared to sCRT. Conclusion We have found that less than half of this study population were treated radically while the other half received palliative treatment. And only few patients received best supportive care. Radically treated patients had higher progression free survival and overall survival durations compared to palliative and supportive treatment.

scholarly journals Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma

2020 ◽  
pp. JCO.20.02259
Author(s):  
Paul G. Richardson ◽  
Albert Oriol ◽  
Alessandra Larocca ◽  
Joan Bladé ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.

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