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Purpose: Assess safety and efficacy of nivolumab plus nab -paclitaxel and gemcitabine in patients with locally advanced/metastatic pancreatic cancer in a two-part, open-label, phase I trial., Patients and Methods: Fifty chemotherapy-naive patients received nab -paclitaxel 125 mg/m 2 plus gemcitabine 1,000 mg/m 2 (days 1, 8, and 15) and nivolumab 3 mg/kg (days 1 and 15) in 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs; part 1) and grade 3/4 treatment-emergent adverse events (TEAEs) or treatment discontinuation due to TEAEs (parts 1/2). Secondary efficacy endpoints were progression-free survival (PFS), overall survival (OS), and response. Assessment of programmed cell death-ligand 1 (PD-L1) expression was an exploratory endpoint; additional biomarkers were assessed post hoc ., Results: One DLT (hepatitis) was reported in part 1 among six DLT-evaluable patients; 48 of 50 patients experienced grade 3/4 TEAEs and 18 discontinued treatment due to TEAEs. One grade 5 TEAE (respiratory failure) was reported. Median [95% confidence interval (CI)] PFS/OS was 5.5 (3.25-7.20 months)/9.9 (6.74-12.16 months) months, respectively [median follow-up for OS, 13.6 months (95% CI, 12.06-23.49 months)]. Overall response rate (95% CI) was 18% (8.6%-31.4%). Median PFS/OS was 5.5/9.7 months (PD-L1 <5%) and 6.8/11.6 months (PD-L1 ≥5%), respectively. Proportion of peripheral Ki67 + CD8 + /CD4 + cells increased significantly from baseline to cycle 3; median peak on-treatment Ki67 + CD8 + T-cell values were higher in responders than in nonresponders., Conclusions: The safety profile of nivolumab plus nab -paclitaxel and gemcitabine at standard doses in advanced pancreatic cancer was manageable, with no unexpected safety signals. Overall, the clinical results of this study do not support further investigation., (©2020 American Association for Cancer Research.)

Background: Treatment options for patients with unresectable locally advanced pancreatic cancer are scarce. Results from a subanalysis of the phase 3 MPACT trial in metastatic pancreatic cancer suggested potential activity of nab-paclitaxel plus gemcitabine against locally advanced pancreatic cancer. The objective of this phase 2 trial was to evaluate safety and efficacy of nab-paclitaxel plus gemcitabine in previously untreated locally advanced pancreatic cancer., Methods: This international, open-label, multicentre, phase 2 trial (LAPACT) took place at 35 sites in five countries (USA, France, Spain, Canada, and Italy). Patients with Eastern Cooperative Oncology Group performance status of up to 1 underwent six cycles of induction with nab-paclitaxel 125 mg/m 2 plus gemcitabine 1000 mg/m 2 (days 1, 8, and 15 of each 28-day cycle). After induction, patients without progressive disease or unacceptable adverse events were eligible to receive continued therapy per investigator's choice: continued nab-paclitaxel plus gemcitabine, chemoradiation, or surgery. The primary endpoint was time to treatment failure; secondary endpoints were disease control rate, overall response rate, progression-free survival, overall survival, safety, and quality of life. The reported efficacy outcomes were analysed in the intention-to-treat population, and safety outcomes were analysed in the treated population. This trial is registered with ClinicalTrials.gov, NCT02301143, and EudraCT, 2014-001408-23 and is complete., Findings: Between April 21, 2015, and April 26, 2018, 107 patients were enrolled in the study. 106 received the study treatment; one patient enrolled but did not receive treatment. 44 (41%) of 107 enrolled patients discontinued induction; the most common reason for discontinuing induction was adverse events (22 [21%] patients). 62 (58%) of 107 enrolled patients completed induction treatment and 47 (44%) patients subsequently received continued treatment per investigator's choice: 12 (11%) continued nab-paclitaxel plus gemcitabine, 18 (17%) received chemoradiation, and 17 (16%) underwent surgery (seven had R0 resection status, nine had R1). 15 (14%) patients completed induction treatment but did not receive continued treatment. Median time to treatment failure was 9·0 months (90% CI 7·3-10·1); median progression-free survival was 10·9 months (90% CI 9·3-11·6), and median overall survival was 18·8 months (90% CI 15·0-24·0). During induction, 83 patients achieved disease control and the disease control rate was 77·6% (90% CI 70·3-83·5). 36 patients had a best response of partial response; the overall response rate during induction was 33·6% (90% CI 26·6-41·5). The most common treatment-emergent adverse events that were grade 3 or higher in the treated population during induction were neutropenia (35 [33%] of 106 patients), anaemia (12 [11%]), and fatigue (11 [10%]). The most common treatment-emergent serious adverse events during induction were pneumonia (five [5%] patients), pyrexia (five [5%]), and febrile neutropenia (three [3%]). No deaths were caused by treatment-related adverse events during the induction phase, and global quality of life was maintained in most patients., Interpretation: The data from this trial support the tolerability and activity of nab-paclitaxel plus gemcitabine for locally advanced pancreatic cancer, and a potential to convert unresectable, locally advanced disease to surgically resectable disease. The safety profile was generally consistent with previous findings., Funding: Celgene., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: This randomized phase 2 trial compared the efficacy and safety of second-line nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with or without the addition of CC-486 (an oral formulation of 5-azacytidine) in patients with advanced-stage, nonsquamous non-small cell lung cancer., Methods: Patients were randomized to receive either nab-paclitaxel 100 mg/m 2 on days 8 and 15 plus CC-486 200 mg daily on days 1 to 14 or single-agent nab-paclitaxel 100 mg/m 2 on days 1 and 8, with both regimens administered every 21 days until tumor progression or unacceptable toxicity. The primary endpoint was progression-free survival. Secondary endpoints included the overall response rate, the disease control rate, and overall survival., Results: Between January 2015 and August 2016, 161 patients were randomized (81 to the combination arm and 80 to the single-agent nab-paclitaxel arm). There was no benefit from the addition of CC-486 to nab-paclitaxel. The median progression-free survival was 3.2 months for the combination and 4.2 months for single-agent nab-paclitaxel (hazard ratio, 1.3; 95% confidence interval, 0.9-1.9). The median overall survival was 8.1 months in the combination arm and 17 months in the single-agent nab-paclitaxel arms (hazard ratio, 1.7; 95% confidence interval, 1.08-2.57). Grade 3 or greater treatment-related, emergent adverse events were reported by 40.5% of patients in the combination arm and by 31.6% of those in the single-agent nab-paclitaxel arm., Conclusions: Single-agent nab-paclitaxel was associated with promising outcomes and a tolerable safety profile as second-line treatment for patients with advanced-stage, nonsquamous non-small cell lung cancer. There was no benefit from the addition of CC-486 to nab-paclitaxel., (© 2018 American Cancer Society.)

Background: Limited data on elderly patients with squamous advanced non-small cell lung cancer (NSCLC) preclude optimal treatment. Here, we report the outcomes of a retrospective analysis of a subset of patients ≥70 years with squamous histology from the Phase III trial that evaluated nab-paclitaxel/carboplatin vs paclitaxel/carboplatin., Patients and Methods: Patients with stage IIIB/IV NSCLC received (1:1) nab-paclitaxel 100 mg/m 2 on days 1, 8, and 15 or paclitaxel 200 mg/m 2 on day 1, both with carboplatin area under the curve 6 mg×min/mL on day 1 every 3 weeks. The primary endpoint was independently assessed overall response rate as per the Response Evaluation Criteria in Solid Tumors v1.0. Secondary endpoints included progression-free survival, overall survival, and safety., Results: Sixty-five patients ≥70 years with squamous histology were included (nab-paclitaxel/carboplatin, n=35; paclitaxel/carboplatin, n=30). nab-Paclitaxel/carboplatin vs paclitaxel/carboplatin, respectively, resulted in an overall response rate of 46% vs 20% (response rate ratio, 2.29, P =0.029) and a median overall survival of 16.9 vs 8.6 months (hazard ratio, 0.50, P =0.018). No difference was observed in median progression-free survival (5.7 months for both). Incidences of grade 3/4 neutropenia (50% vs 63%), leukopenia (29% vs 37%), fatigue (3% vs 13%), and peripheral neuropathy (3% vs 13%) were lower, but those of thrombocytopenia (21% vs 10%) and anemia (21% vs 7%) were higher with nab-paclitaxel/carboplatin vs paclitaxel/carboplatin., Conclusion: nab-Paclitaxel/carboplatin was efficacious and tolerable in patients ≥70 years with squamous NSCLC. These results build upon prior analyses, indicating that nab-paclitaxel/carboplatin is effective for this difficult-to-treat patient subgroup., Competing Interests: Disclosure TC, AK, TJO: employment or leadership position and stock ownership, Celgene Corporation. MEO: advisory role, Celgene, GSK, BMS, Pierre Fabre, Medimmune, MSD, Pfizer, Daichii Sankyo. MAS: honoraria and speaker’s bureau, Celgene. PEP: advisory board member of Celgene, Boehringer Ingelheim, Halozyme, Teva, Clovis Oncology, Eli Lilly. The authors report no other conflicts of interest in this work.

Aim: Evaluate quality of life (QoL) in patients with advanced non-small cell lung cancer treated with second or third line nab-paclitaxel ± durvalumab. Patients & methods: Longitudinal QoL was assessed using Lung Cancer Symptom Scale, EuroQoL Five-Dimensions Five-Levels and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core. Results: QoL was generally stable through eight treatment cycles (both arms). Clinically meaningful improvement from baseline was noted in Lung Cancer Symptom Scale (overall constitutional score and three-item index [nab-paclitaxel + durvalumab]) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core (global health status/QoL and emotional functioning [both arms] and pain [nab-paclitaxel + durvalumab]) analyses. EuroQoL Five-Dimensions Five-Levels domains were stable/improved or completely resolved at least once in 19-56% and 9-51% of patients, respectively. Conclusion: While QoL trends were promising, additional data are required to support these regimens in this setting. [ABSTRACT FROM AUTHOR]

The phase 4 ABOUND.70+ trial assessed the safety and efficacy of nab-paclitaxel/carboplatin continuously or with a 1-week break between cycles in elderly patients with advanced non-small cell lung cancer (NSCLC). Patients ≥70 years with locally advanced/metastatic NSCLC were randomized 1:1 to first-line nab-paclitaxel days 1, 8, 15 plus carboplatin day 1 of a 21-day cycle (21d) or the same nab-paclitaxel/carboplatin regimen with a 1-week break between cycles (21d + break; 28d). The primary endpoint was the percentage of patients with grade ≥ 2 peripheral neuropathy (PN) or grade ≥ 3 myelosuppression. Other key endpoints included progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). A total of 143 patients were randomized (71 to 21d, 72 to 21d + break). The percentage of patients with grade ≥ 2 PN or grade ≥ 3 myelosuppression was similar between the 21d and 21d + break arms (76.5 and 77.1%; P = 0.9258). Treatment exposure was lower in the 21d arm compared with the 21d + break arm. Median OS was 15.2 and 16.2 months [hazard ratio (HR) 0.72, 95% CI 0.44–1.19; P = 0.1966], median PFS was 3.6 and 7.0 months (HR 0.48, 95% CI 0.30–0.76; P < 0.0019), and ORR was 23.9 and 40.3% (risk ratio 1.68, 95% CI 1.02–2.78; P = 0.0376) in the 21d and 21d + break arms, respectively. In summary, the 1-week break between treatment cycles significantly improved PFS and ORR but did not significantly reduce the percentage of grade ≥ 2 PN or grade ≥ 3 myelosuppression. Overall, the findings support the results of prior subset analyses on the safety and efficacy of first-line nab-paclitaxel/carboplatin in elderly patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Introduction: The phase II ABOUND.PS2 study (NCT02289456) assessed safety/tolerability of a first-line modified nab-paclitaxel/carboplatin regimen for patients with advanced non-small cell lung cancer (NSCLC) and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2. Methods: Chemotherapy-naive patients with stage IIIB/IV NSCLC and ECOG PS 2 received four cycles of nab-paclitaxel 100 mg/m2 days 1 and 8 plus carboplatin area under the curve 5 day 1 q3w (induction). Patients without progression received nab-paclitaxel monotherapy (100 mg/m2 days 1 and 8 q3w) until progression/unacceptable toxicity. Primary endpoint: percentage of patients discontinuing induction due to treatment-emergent adverse events (TEAEs). Results: 11/40 treated patients (27.5%; 95% CI, 14.60–43.89) discontinued chemotherapy induction due to TEAEs; 16/40 (40.0%) continued nab-paclitaxel monotherapy. Median progression-free and overall survival were 4.4 (95% CI, 2.99–7.00) and 7.7 (95% CI, 4.93–13.17) months. Grade 3/4 TEAEs during induction included neutropenia (22.5%), anemia (17.5%), thrombocytopenia (5.0%), and peripheral neuropathy (2.5%). Conclusion: This nab-paclitaxel–based regimen was tolerable in patients with advanced NSCLC and ECOG PS 2, with efficacy comparable to historical chemotherapy data. [ABSTRACT FROM AUTHOR]

Background: A partial response according to the Response Evaluation Criteria in Solid Tumors includes a wide range of changes in tumor size. This study evaluated whether further specification of tumor reduction based on the depth of response (DpR) would provide a more precise association with outcomes for patients with non-small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy.Methods: A retrospective analysis was performed for the randomized phase 3 CA031 trial in patients with NSCLC treated with carboplatin in combination with nab-paclitaxel or solvent-based paclitaxel. Quartiles according to the maximum tumor reduction from the baseline were defined (quartile 1 [Q1], >0% to 25%; quartile 2 [Q2], >25% to 50%; quartile 3 [Q3], >50% to 75%; and quartile 4 [Q4], >75%) and were compared with those patients with no tumor reduction (NTR). The primary objective was to evaluate the association between DpR and overall survival (OS).Results: Of the 1052 patients enrolled in the CA031 trial, 959 (91%) were evaluable, and they included 365 (38.1%) who were classified as Q1, 327 (34.1%) who were classified as Q2, 131 (13.7%) who were classified as Q3, and 34 (3.5%) who were classified as Q4; 102 had NTR (10.6%). The median OS values for patients in the NTR, Q1, Q2, Q3, and Q4 groups were 4.8, 10.4, 14.5, 19.3, and 23.5 months, respectively. The maximum DpR on treatment was an independent predictor of improved OS in comparison with patients with NTR; the hazard ratio decreased from 0.43 in Q1 to 0.16 in Q4.Conclusions: DpR was strongly associated with OS in patients with NSCLC receiving first-line platinum-based therapy. Additional studies may help to define the role of DpR in solid tumors. [ABSTRACT FROM AUTHOR]