Consolidation With Pembrolizumab and Nab-Paclitaxel After Induction Platinum-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer.
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ABSTRACT: Background
Induction with four cycles of platinum-based chemotherapy was the standard of care for metastatic non-small cell lung cancer (NSCLC) until the approval of immune checkpoint blockade (ICB) in the first-line setting. Switch maintenance therapy has shown promise in improving survival by exposing patients to novel, non-cross-resistant agents earlier in their treatment course.Methods
We performed this open-label, three-arm, randomized phase II study (NCT02684461) to evaluate three sequences of consolidation with pembrolizumab and nab-paclitaxel in patients without progressive disease post induction chemotherapy. Consolidation was either sequential with pembrolizumab for four cycles followed by nab-paclitaxel for four cycles (P→A), nab-paclitaxel followed by pembrolizumab (A→P), or concurrent nab-paclitaxel and pembrolizumab for four cycles (AP).Results
Twenty patients were randomized before the study was closed early due to the approval of first-line checkpoint inhibitors. We found that consolidation is feasible and well tolerated, with 30% of patients experiencing grade 3 toxicity. The median progression-free survival and OS in months (95% CI) in P→A were 10.1 (1.5-NR), 27.6 (1.7-NR); 8.4 (1.2-9.0), 12.7 (4.4-NR) in A→P; and 10.2 (5.1-NR), NR. Quality of life as measured by FACT-L improved in the majority of patients during the course of the study.Conclusion
Sequential and concurrent consolidation regimens are well tolerated and have encouraging overall survival in patients with metastatic NSCLC.
SUBMITTER: Patel SA
PROVIDER: S-EPMC8074674 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:Longitudinal data on the impact of treatment on quality of life (QoL) in advanced non-small cell lung cancer (NSCLC) are limited. In this palliative setting, treatment that does not deteriorate QoL is key. Here we report longitudinal QoL in patients with squamous NSCLC, receiving ?4 cycles of nab-paclitaxel/carboplatin combination chemotherapy. Methods:Patients received nab-paclitaxel 100 mg/m2 days 1, 8, 15 + carboplatin area under the curve 6 mg•min/mL day 1 (q3w) for four cycles. QoL was assessed by the Lung Cancer Symptom Scale (LCSS) and Euro-QoL-5 Dimensions-5 Levels (EQ-5D-5L) at baseline and each cycle (day 1). Results:Two-hundred and six lesion-response-evaluable patients completed baseline + ?1 postbaseline QoL assessment and were QoL evaluable. LCSS average total score and symptom burden index improved from baseline throughout four cycles. In the LCSS pulmonary symptoms score, 46% of patients reported clinically meaningful improvement (?10 mm visual analog scale) from baseline. Individual EQ-5D-5L dimensions remained stable/improved in ?83% of patients; ?33% reported complete resolution of baseline problems at least once during four cycles. Generally, responders (unconfirmed complete/partial response) had higher scores vs nonresponders. Conclusion:In patients with squamous NSCLC, four cycles of nab-paclitaxel/carboplatin demonstrated clinically meaningful QoL improvements, with greater benefits in responders vs nonresponders.
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| S-EPMC4402061 | biostudies-literature
Project description:ObjectivesPlatinum-based chemotherapy for advanced non-small-cell lung cancer (NSCLC) has modest benefit overall, but has the potential to amplify immune responses. In cohorts A-C of the multicohort phase 1/2 study KEYNOTE-021 (Clinicaltrials.gov, NCT02039674), we evaluated combinations of platinum-doublet chemotherapy with the anti-programmed death 1 monocloncal antibody pembrolizumab.Materials and methodsPatients with previously untreated, advanced NSCLC without EGFR/ALK aberrations were randomized to pembrolizumab 2 or 10 mg/kg Q3W plus carboplatin area under the serum concentration-time curve (AUC) 6 mg/mL/min plus paclitaxel 200 mg/m2 (cohort A, any histology), carboplatin AUC 6 mg/mL/min plus paclitaxel 200 mg/m2 plus bevacizumab 15 mg/kg (cohort B, non-squamous), or carboplatin AUC 5 mg/mL/min plus pemetrexed 500 mg/m2 (cohort C, non-squamous) for 4 cycles followed by maintenance pembrolizumab (cohort A), pembrolizumab plus bevacizumab (cohort B), or pembrolizumab plus pemetrexed (cohort C). Response was assessed by blinded independent central review.ResultsOverall, 74 patients were randomized; median follow-up was 21.4, 16.4, and 17.4 months in cohorts A, B, and C, respectively. No dose-limiting toxicities occurred in any cohort at either pembrolizumab dose. Most frequent treatment-related adverse events (AEs) were alopecia, fatigue, and nausea. Treatment-related grade 3/4 AEs occurred in 40%, 42%, and 46% of patients in cohorts A, B, and C, respectively; AEs with possible immune etiology occurred in 24%, 50%, and 38% of patients, respectively. Objective response rates were 48%, 56%, and 75% in cohorts A, B, and C, respectively.ConclusionPembrolizumab in combination with carboplatin-paclitaxel and with pemetrexed-carboplatin yielded encouraging antitumor activity and toxicity consistent with known toxicities of platinum-based chemotherapy or pembrolizumab monotherapy.
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Project description:BackgroundIn the recent phase III trial MPACT the combination of gemcitabine and nab-paclitaxel (Gem/NabP) showed increased overall survival compared to gemcitabine alone in the treatment of advanced pancreatic ductal adenocarcinoma (aPDA). Until now there has been limited information on the clinical benefit and toxicity of the combination regimen in a real world setting. In addition the value for patients with locally advanced rather than metastatic aPDA has been unclear, since the former category of patients was not included in the MPACT trial.MethodsA multicentre retrospective observational study in the South Eastern Region of Sweden was performed, with the first 75 consecutive patients diagnosed with aPDA (both locally advanced and metastatic disease) who received first-line treatment with Gem/NabP.ResultsIn the overall population median progression free survival (PFS) and overall survival (OS) were 5.2 (3.4-7.0 95% CI) and 10.9 (7.8-14.0 95% CI) months, respectively. Patients with metastatic disease displayed a median OS of 9.4 (4.9-13.9) and a median PFS of 4.5 (3.3-5.7) months whereas the same parameters in the locally advanced subgroup were 17.1 (7.6-26.6) and 6.8 (5.2-8.4) months, respectively. Grade 3-4 hematologic toxicity was recorded: Neutropenia, leukopenia, thrombocytopenia, and anaemia were observed in 23, 20, 5, and 4% of patients, respectively. Dose reductions were performed in 80% of the patients.ConclusionThis study confirms the effectiveness and safety of first-line Gem/NabP in both locally advanced and metastatic PDA in a real world setting.
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Project description:Background Pembrolizumab has been shown to have a powerful benefit for locally advanced or metastatic esophageal cancer. The aim of present study was to evaluate the efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy for locally advanced and potentially resectable esophageal squamous cell carcinoma (ESCC). Methods Patients diagnosed with clinical stage III-IV ESCC and have a chance of resectability at Fujian Provincial Hospital were included into this study. Patients received pembrolizumab in combination with paclitaxel and nedaplatin as induction therapy once every 3 weeks in the first stage. After 4 cycles of pembrolizumab therapy, the patients then chose to undergo radical surgery (group A), radical radiotherapy (group B), or neither (group C). In the third stage, maintenance treatment with pembrolizumab was administered to all patients. Results A total of 39 patients (33 male and 6 female) with a median age of 64 years were included. After immune response evaluation in the first stage, 34 (87.2%) patients achieved immune partial response (iPR), and 5 (12.8%) patients achieved immune stable disease (iSD). The objective response rate (ORR) was 87.2% (34/39), and the disease control rate (DCR) was 100%. In the second stage, 22 patients received radical surgery, all of whom achieved R0 resection. The major pathological response (MPR) rate was 68.2% (15/22), and the pathological complete response (pCR) rate was 45.5% (10/22). Of the patients, 9 chose radiotherapy as the radical therapeutic method and 8 chose not to undergo any radical therapy. The median period of pembrolizumab therapy was 8 cycles (4–22 cycles). The median follow-up time was 14 months (3–34 months). The median overall survival and progression-free survival (PFS) times were not reached. The incidence of severe adverse events (AEs) (grade ≥3) was 15.4% (6/39). Conclusions Pembrolizumab combined with paclitaxel and platinum for locally advanced and potentially resectable ESCC has a high ORR, high surgical conversion, MPR, pCR, and R0 resection rates, and tolerable AEs. Also, pembrolizumab could provide good benefits in sequential treatment with radical radiotherapy or maintenance therapy.
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Project description:ObjectiveTo evaluate the effectiveness and safety of nab-paclitaxel plus platinum as first-line chemotherapy for ovarian cancer (OC).MethodsPatients administered platinum combined with nab-paclitaxel as first-line chemotherapy for epithelial OC, fallopian tube cancer, or primary peritoneal cancer from July 2018 to December 2021 were retrospectively evaluated. The primary outcome was progression-free survival (PFS). Adverse events (AEs) were examined. Subgroup analysis was performed.ResultsSeventy-two patients (median age, 54.5 years; range, 20.0-79.0 years) were evaluated, including 12 and 60 administered neoadjuvant therapy and primary surgery with subsequent chemotherapy, respectively. The median follow-up duration was 25.6 months, and the median PFS was 26.7 (95% confidence interval [CI]=24.0-29.3) months in the whole patient population. In the neoadjuvant subgroup, the median PFS was 26.7 (95% CI=22.9-30.5) months vs. 30.1 (95% CI=23.1-37.1) months in the primary surgery subgroup. Twenty-seven patients were administered nab-paclitaxel plus carboplatin and had a median PFS of 30.3 (95% CI=not available [NA]-NA) months. The commonest grade 3-4 AEs included anemia (15.3%), white blood cell decreased (11.1%), and neutrophil count decreased (20.8%). No drug-related hypersensitivity reactions occurred.ConclusionNab-paclitaxel plus platinum as first-line treatment in OC was associated with a favorable prognosis and was tolerable in patients with OC.
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Project description:Background: The standard therapy for advanced stage non-small cell lung cancer (NSCLC) with no actionable gene alterations is a platinum-based chemotherapy doublet and immune checkpoint blocker (ICB), either concurrently or sequentially, followed by docetaxel at the time of tumor progression. However, more effective treatments are needed. We evaluated the nab-paclitaxel and durvalumab combination in patients with previously treated advanced stage NSCLC. Methods: Patients with advanced stage NSCLC previously treated with one line of platinum-based doublet with or without an ICB and no activating EGFR mutations or ALK translocations received nab-paclitaxel 100 mg/m2 (days 1 and 8) plus durvalumab 1,125 mg (day 15) every 21 days. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and safety. Results: Between February 2016 and December 2016, 79 patients were enrolled. The median age was 63 years. Most patients were males (68.4%), had non-squamous histology (69.6%), and had no prior ICB treatment (88.6%). The median PFS was 4.5 months; median OS was 10.1 months. A post hoc analysis of survival by prior ICB treatment revealed a median PFS and OS of 4.4 and 9.9 months, respectively, in ICB-naive patients and 6.9 months and not estimable, respectively, in patients previously treated with ICB. The most common treatment-emergent adverse events were asthenia (46.2%) and diarrhea (34.6%); four treatment-related deaths (5.1%) occurred. Conclusions: The nab-paclitaxel and durvalumab combination is feasible and demonstrated antitumor activity without new safety signals. Additional studies using taxanes and ICB in patients with previously treated NSCLC are warranted. Clinical Trial Registration: ClinicalTrials.gov registration (NCT02250326). EudraCT number: 2014-001105-41.
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Project description:BackgroundPlatinum-based chemotherapy remains a first-line standard of care for approximately 30% of patients with non-small cell lung cancer (NSCLC) not harboring a druggable alteration. Favorable efficacy and safety of the nab-paclitaxel/carboplatin (nab-P/C) combination was shown in the pivotal phase 3 trial. However, information on effectiveness of nab-P/C in a real-world setting in Germany is missing. The NEPTUN study prospectively investigated the effectiveness and safety of nab-P/C in patients with advanced NSCLC in a real-world setting.MethodsPatients with advanced or metastatic NSCLC received first-line nab-P/C according to clinical routine. The primary endpoint was 6-month progression-free survival rate (PFS6). Other endpoints included further effectiveness parameters, safety and quality of life. Data were analyzed descriptively.Results408 patients were enrolled. PFS6 was 40.8% (95% confidence interval [CI], 35.3-46.2); median PFS was 5.2 months (95% CI, 4.5-5.7). overall response rate was 41.5% (95% CI, 36.3-46.8). Median overall survival (OS) was 10.5 months (95% CI, 9.2-11.6). Subgroup analyses revealed median OS for squamous versus non-squamous histology (11.8 months [95% CI, 9.2-13.8] vs. 9.6 months [95% CI, 7.7-11.2]) and age ≥70 versus <70 years (11.7 months [95% CI, 9.4-14.3] vs. 9.6 months [95% CI, 7.5-11.2]). Most common treatment-emergent adverse events (TEAEs) were anemia (26.5%), leukopenia (25.7%), and thrombocytopenia (16.6%). Mostly reported grade 3/4 TEAEs were leukopenia (10.2%), anemia (8.6%), and pneumonia (5.1%). nab-paclitaxel-related deaths as reported by the investigator occurred in 0.8% of patients.ConclusionThese real-world data support the effectiveness and safety of nab-P/C as first-line treatment for patients with advanced NSCLC independent of tumor histology. The results are comparable with the pivotal phase 3 trial. No new safety signals emerged.
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