nab-paclitaxel/carboplatin induction in squamous NSCLC: longitudinal quality of life while on chemotherapy

Michael Thomas,1,2 David R Spigel,3 Robert M Jotte,4 Michael McCleod,5 Mark A Socinski,6 Ray D Page,7 Laurent Gressot,8 Jeanna Knoble,9 Oscar Juan,10 Daniel Morgensztern,11 Dolores Isla,12 Edward S Kim,13 Howard West,14 Amy Ko,15 Teng Jin Ong,15 Nataliya Trunova,15 Cesare Gridelli16 On behalf of ABOUND.sqm investigators 1Department of Thoracic Oncology/Internal Medicine, Thoraxklinik im Universitätsklinikum Heidelberg, 2Translational Lung Research Center Heidelberg, Heidelberg, Germany; 3Sarah Cannon Research Institute, Nashville, TN, 4Department of Medical Oncology/Hematology, Rocky Mountain Cancer Centers, Denver, CO, 5Florida Cancer Specialists, Fort Myers, 6Florida Hospital Cancer Institute, Orlando, FL, 7The Center for Cancer and Blood Disorders, Fort Worth, 8North Cypress Cancer Center, Cypress, TX, 9The Mark H. Zangmeister Center, Columbus, OH, USA; 10Department of Medical Oncology, Hospital Universitari i Politécnic La Fe, Valencia, Spain; 11Department of Medical Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; 12Department of Medical Oncology, University Hospital Lozano Blesa, Zaragoza, Spain; 13Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, 14Thoracic Oncology Program, Swedish Cancer Institute, Seattle, WA, 15Celgene Corporation, Summit, NJ, USA; 16Department of Oncology/Hematology, S.G. Moscati Hospital, Avellino, Italy 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. Keywords: nab-paclitaxel, non-small cell lung cancer, quality of life, response, squamou

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial

BACKGROUND: As lenalidomide becomes increasingly established for upfront treatment of multiple myeloma, patients refractory to this drug represent a population with an unmet need. The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma. We aimed to assess the efficacy and safety of this triplet regimen in patients with relapsed or refractory multiple myeloma who previously received lenalidomide. METHODS: We did a randomised, open-label, phase 3 trial at 133 hospitals and research centres in 21 countries. We enrolled patients (aged 6518 years) with a diagnosis of multiple myeloma and measurable disease, an Eastern Cooperative Oncology Group performance status of 0-2, who received one to three previous regimens, including a lenalidomide-containing regimen for at least two consecutive cycles. We randomly assigned patients (1:1) to bortezomib and dexamethasone with or without pomalidomide using a permutated blocked design in blocks of four, stratified according to age, number of previous regimens, and concentration of \u3b2(2) microglobulin at screening. Bortezomib (1\ub73 mg/m(2)) was administered intravenously until protocol amendment 1 then either intravenously or subcutaneously on days 1, 4, 8, and 11 for the first eight cycles and subsequently on days 1 and 8. Dexamethasone (20 mg [10 mg if age >75 years]) was administered orally on the same days as bortezomib and the day after. Patients allocated pomalidomide received 4 mg orally on days 1-14. Treatment cycles were every 21 days. The primary endpoint was progression-free survival in the intention-to-treat population, as assessed by an independent review committee. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered at ClinicalTrials.gov, number NCT01734928; patients are no longer being enrolled. FINDINGS: Between Jan 7, 2013, and May 15, 2017, 559 patients were enrolled. 281 patients were assigned pomalidomide, bortezomib, and dexamethasone and 278 were allocated bortezomib and dexamethasone. Median follow-up was 15\ub79 months (IQR 9\ub79-21\ub77). Pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared with bortezomib and dexamethasone (median 11\ub720 months [95% CI 9\ub766-13\ub773] vs 7\ub710 months [5\ub788-8\ub748]; hazard ratio 0\ub761, 95% CI 0\ub749-0\ub777; p<0\ub70001). 278 patients received at least one dose of pomalidomide, bortezomib, and dexamethasone and 270 patients received at least one dose of bortezomib and dexamethasone, and these patients were included in safety assessments. The most common grade 3 or 4 treatment-emergent adverse events were neutropenia (116 [42%] of 278 patients vs 23 [9%] of 270 patients; nine [3%] vs no patients had febrile neutropenia), infections (86 [31%] vs 48 [18%]), and thrombocytopenia (76 [27%] vs 79 [29%]). Serious adverse events were reported in 159 (57%) of 278 patients versus 114 (42%) of 270 patients. Eight deaths were related to treatment; six (2%) were recorded in patients who received pomalidomide, bortezomib, and dexamethasone (pneumonia [n=2], unknown cause [n=2], cardiac arrest [n=1], cardiorespiratory arrest [n=1]) and two (1%) were reported in patients who received bortezomib and dexamethasone (pneumonia [n=1], hepatic encephalopathy [n=1]). INTERPRETATION: Patients with relapsed or refractory multiple myeloma who previously received lenalidomide had significantly improved progression-free survival when treated with pomalidomide, bortezomib, and dexamethasone compared with bortezomib and dexamethasone. Adverse events accorded with the individual profiles of pomalidomide, bortezomib, and dexamethasone. This study supports use of pomalidomide, bortezomib, and dexamethasone as a treatment option in patients with relapsed or refractory multiple myeloma who previously received lenalidomide. FUNDING: Celgene

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial

Background As lenalidomide becomes increasingly established for upfront treatment of multiple myeloma, patients refractory to this drug represent a population with an unmet need. The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma. We aimed to assess the efficacy and safety of this triplet regimen in patients with relapsed or refractory multiple myeloma who previously received lenalidomide.Methods We did a randomised, open-label, phase 3 trial at 133 hospitals and research centres in 21 countries. We enrolled patients (aged >= 18 years) with a diagnosis of multiple myeloma and measurable disease, an Eastern Cooperative Oncology Group performance status of 0-2, who received one to three previous regimens, including a lenalidomide-containing regimen for at least two consecutive cycles. We randomly assigned patients (1:1) to bortezomib and dexamethasone with or without pomalidomide using a permutated blocked design in blocks of four, stratified according to age, number of previous regimens, and concentration of beta(2) microglobulin at screening. Bortezomib (1.3 mg/m(2)) was administered intravenously until protocol amendment 1 then either intravenously or subcutaneously on days 1,4, 8, and 11 for the first eight cycles and subsequently on days 1 and 8. Dexamethasone (20 mg [10 mg if age >75 years]) was administered orally on the same days as bortezomib and the day after. Patients allocated pomalidomide received 4 mg orally on days 1-14. Treatment cycles were every 21 days. The primary endpoint was progression-free survival in the intention-to-treat population, as assessed by an independent review committee. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered at ClinicalTrials.gov, number NCT01734928; patients are no longer being enrolled.Findings Between Jan 7, 2013, and May 15,2017,559 patients were enrolled. 281 patients were assigned pomalidomide, bortezomib, and dexamethasone and 278 were allocated bortezomib and dexamethasone. Median follow-up was 15.9 months (IQR 9.9-21.7). Pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared with bortezomib and dexamethasone (median 11.20 months [95% CI 9.66-13-73] vs 7.10 months [5.88-8-48]; hazard ratio 0.61, 95% CI 0.49-0-77; p<0-0001). 278 patients received at least one dose of pomalidomide, bortezomib, and dexamethasone and 270 patients received at least one dose of bortezomib and dexamethasone, and these patients were included in safety assessments. The most common grade 3 or 4 treatment-emergent adverse events were neutropenia (116 [42%] of 278 patients vs 23 [9%1 of 270 patients; nine p.m vs no patients had febrile neutropenia), infections (86 [31%] vs 48 118%1), and thrombocytopenia (76 [27%1 vs 79 [29%]). Serious adverse events were reported in 159 (57%) of 278 patients versus 114 (42%) of 270 patients. Eight deaths were related to treatment; six (2%) were recorded in patients who received pomalidomide, bortezomib, and dexamethasone (pneumonia [n=2], unknown cause [n=2], cardiac arrest [n=1], cardiorespiratory arrest [n=11) and two (1%) were reported in patients who received bortezomib and dexamethasone (pneumonia In=11, hepatic encephalopathy [n=1.]).Interpretation Patients with relapsed or refractory multiple myeloma who previously received lenalidomide had significantly improved progression-free survival when treated with pomalidomide, bortezomib, and dexamethasone compared with bortezomib and dexamethasone. Adverse events accorded with the individual profiles of pomalidomide, bortezomib, and dexamethasone. This study supports use of pomalidomide, bortezomib, and dexamethasone as a treatment option in patients with relapsed or refractory multiple myeloma who previously received lenalidomide. Copyright (C) 2019 Elsevier Ltd. All rights reserved