Durvalumab after chemo-radiotherapy in stage III non-small cell lung cancer.
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ABSTRACT:
SUBMITTER: Chiramel J
PROVIDER: S-EPMC5949435 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Stage III non-small cell lung cancer (NSCLC) has a dismal prognosis, with only 15-20% of patients alive at 5?years after concomitant chemo-radiotherapy, which represents the standard treatment. Targeting immune-checkpoint inhibitors represents a standard option for advanced NSCLC. Improvements in understanding of the immune profile of NSCLC has led to the development of immunotherapeutic strategies, including inhibitory molecules responsible for abrogating an anticancer immune response such as programmed cell-death 1 and programmed cell-death ligand 1. A recently published phase III trial (PACIFIC) showed for the first time an improved overall survival in stage III NSCLC patients with consolidative durvalumab. The aim of this review is to summarize and discuss the clinical evidence for the use of durvalumab in stage III NSCLC, with a brief overview on future perspectives in this setting.
| S-EPMC6831969 | biostudies-literature
Project description:Despite adequate treatment, 50% of stage III locally advanced inoperable non-small cell lung cancer (NSCLC) patients have a locoregional relapse. Local control on early stages on the contrary, is as high as 85-90% with stereotactic body radiotherapy (SBRT). The addition of SBRT to conventional chemoradiation or its use in monotherapy in stage III NSCLC is a novel strategy to decrease local failure that has been explored by various authors. This is a systematic review of studies using SBRT in inoperable stage III NSCLC. Search results obtained 141 articles of which only 6 original studies were pointed as relevant. Three of these studies were prospective, of which 2 were phase I dose-scalation studies and remaining 3 were retrospective. In summary, SBRT outcomes on 134 patients were included. Median dose in the SBRT treatment was 22.5 Gy in 2 to 7 fractions. Obtained global toxicity was 3.7% grade 5 and 14.17% grade 3. Dose-escalation studies proposed a 2 fraction SBRT schedule of 20-24 Gy, obtaining a 78% local control rate at 1 year and an OS of 67%. Initial improvement in local control with this innovative therapeutic strategy has led to ongoing phase II and III clinical trials that will evaluate the efficiency of SBRT in stage III NSCLC clinical scenario.
| S-EPMC7867744 | biostudies-literature
Project description:Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice.
| S-EPMC4493429 | biostudies-literature
Project description:BackgroundSalvage surgery following definitive radiotherapy or systemic treatment has become a feasible treatment option in selected patients with advanced initially unresectable non-small cell lung cancer. Recent clinical trials of neoadjuvant treatment have showed that surgery following immuno-chemotherapy is safely performed. Here, we present the first case of salvage surgery following immuno-chemotherapy with concurrent definitive radiotherapy for advanced lung large cell carcinoma.Case presentationA 44-year male was admitted to our hospital for salvage surgery. Ten months prior to this administration, he had been diagnosed with unresectable large cell carcinoma with malignant pericardial effusion (clinical stage IVA/T3N2M1A; no driver-gene alteration) originating from the right upper lobe (RUL). Due to rapid intrabronchial tumor growth causing severe dyspnea, emergency bronchial stenting in the right main bronchus using an expandable metallic stent had been performed. Thereafter, he had received immuno-chemotherapy with concurrent definitive radiotherapy. Despite dramatic radiographic response, he had suffered from persistent and refractory Pseudomonas aeruginosa lung infection associated with bronchial stent placement. As pericardial effusion had disappeared and no distant metastasis had developed, he was diagnosed with a potentially curable disease and was referred to our hospital. An extended sleeve resection was successfully performed, and pathological sections revealed that pathologic complete response was achieved with immuno-chemo-radiotherapy. The patient received no subsequent treatment, and is alive without tumor recurrence at 8 months after surgery.ConclusionsSalvage surgery following immuno-chemotherapy with concurrent definitive radiotherapy for advanced non-small cell lung cancer may be feasible in selected patients, and may be considered as a treatment option to control local disease.
| S-EPMC8782972 | biostudies-literature
Project description: Not available
| S-EPMC5943223 | biostudies-literature
Project description:In this manuscript, developments in the techniques, clinical outcome, toxicity, and future perspectives of SBRT for medically inoperable and operable early stage NCSLC are discussed. SBRT is well tolerated and has limited and acceptable side effects. It has evolved as a standard of care for medically inoperable patients. These excellent results taken together with the morbidity and mortality associated with surgery, might also lead to changes in the treatment for operable patients.
| S-EPMC5658902 | biostudies-literature
Project description:BackgroundIn the PACIFIC trial, durvalumab significantly improved progression-free and overall survival (PFS/OS) versus placebo, with manageable safety, in unresectable, stage III non-small-cell lung cancer (NSCLC) patients without progression after chemoradiotherapy (CRT). We report exploratory analyses of outcomes by tumour cell (TC) programmed death-ligand 1 (PD-L1) expression.Patients and methodsPatients were randomly assigned (2:1) to intravenous durvalumab 10 mg/kg every 2 weeks or placebo ≤12 months, stratified by age, sex, and smoking history, but not PD-L1 status. Where available, pre-CRT samples were tested for PD-L1 expression (immunohistochemistry) and scored at pre-specified (25%) and post hoc (1%) TC cut-offs. Treatment-effect hazard ratios (HRs) were estimated from unstratified Cox proportional hazards models (Kaplan-Meier-estimated medians).ResultsIn total, 713 patients were randomly assigned, 709 of whom received at least 1 dose of study treatment durvalumab (n = 473) or placebo (n = 236). Some 451 (63%) were PD-L1-assessable: 35%, 65%, 67%, 33%, and 32% had TC ≥25%, <25%, ≥1%, <1%, and 1%-24%, respectively. As of 31 January 2019, median follow-up was 33.3 months. Durvalumab improved PFS versus placebo (primary-analysis data cut-off, 13 February 2017) across all subgroups [HR, 95% confidence interval (CI); medians]: TC ≥25% (0.41, 0.26-0.65; 17.8 versus 3.7 months), <25% (0.59, 0.43-0.82; 16.9 versus 6.9 months), ≥1% (0.46, 0.33-0.64; 17.8 versus 5.6 months), <1% (0.73, 0.48-1.11; 10.7 versus 5.6 months), 1%-24% [0.49, 0.30-0.80; not reached (NR) versus 9.0 months], and unknown (0.59, 0.42-0.83; 14.0 versus 6.4 months). Durvalumab improved OS across most subgroups (31 January 2019 data cut-off; HR, 95% CI; medians): TC ≥ 25% (0.50, 0.30-0.83; NR versus 21.1 months), <25% (0.89, 0.63-1.25; 39.7 versus 37.4 months), ≥1% (0.59, 0.41-0.83; NR versus 29.6 months), 1%-24% (0.67, 0.41-1.10; 43.3 versus 30.5 months), and unknown (0.60, 0.43-0.84; 44.2 versus 23.5 months), but not <1% (1.14, 0.71-1.84; 33.1 versus 45.6 months). Safety was similar across subgroups.ConclusionsPFS benefit with durvalumab was observed across all subgroups, and OS benefit across all but TC <1%, for which limitations and wide HR CI preclude robust conclusions.
| S-EPMC8412232 | biostudies-literature
Project description: Not available
| S-EPMC5949402 | biostudies-literature
Project description:Background and purposeRadiation-esophagitis and weight loss are frequently observed toxicities in patients treated with concurrent chemo-radiotherapy (CT-RT) for non-small cell lung cancer (NSCLC) and might be related. The purpose was to investigate whether weight loss already starts early after initiation of CT-RT and precedes radiation-esophagitis.Materials and methodsIn a retrospective cohort, weight and esophagitis grade ?2 were assessed during the first weeks of (CT-)RT in patients treated with concurrent (n?=?102) or sequential (n?=?92) therapy. In a prospective validation study, data on body weight, esophagitis grade ?2, nutritional intake and muscle strength were obtained before, during and following CT-RT.ResultsIn the retrospective cohort, early weight loss was observed in concurrently treated patients (p?=?0.002), independent of esophagitis???grade 2. Early weight loss was also observed in the prospective cohort (p?=?0.003) and was not accompanied by decreases in nutritional intake. In addition lower limb muscle strength rapidly declined (p?=?0.042). In the later weeks of treatment, further body weight loss occurred (p?<?0.001) despite increased nutritional supplementation and body weight was only partly recovered after 4 weeks post CT-RT (p?=?0.003).ConclusionsWeight loss during concurrent CT-RT for NSCLC starts early and prior to onset of esophagitis, requiring timely and intense nutritional rehabilitation.
| S-EPMC4053563 | biostudies-literature
Project description:The concomitant use of weekly nab-paclitaxel and carboplatin with concurrent radiotherapy was demonstrated to be a safe therapeutic approach in this phase I trial of 10 evaluable patients with stage III NSCLC.Despite the lack of systemic glucocorticoids, there were no reported infusion reactions or cases of peripheral neuropathy in this trial, both of which are known to occur with the use of paclitaxel.Unresectable stage III non-small cell lung cancer (NSCLC) has a 5-year survival rate of 20%, and concurrent chemoradiotherapy results in significant toxicity with the use of current chemotherapeutic agents. nab-Paclitaxel was approved by the U.S. Food and Drug Administration in October 2012 for use along with carboplatin in advanced NSCLC. This study was undertaken to determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of weekly nab-paclitaxel given in combination with carboplatin and concurrent radiotherapy in patients with unresectable stage III NSCLC.Escalating doses of once-weekly nab-paclitaxel were given along with once-weekly carboplatin area under the plasma concentration time curve (AUC) of 2 and concurrent radiotherapy 66 Gy in 33 fractions, followed by 2 cycles of carboplatin and nab-paclitaxel consolidation chemotherapy.Eleven patients were enrolled and received treatment per protocol, with 10 evaluable for efficacy and toxicity. At dose level 1 (nab-paclitaxel 60 mg/m(2)), 2 DLTs were observed: esophagitis and radiation dermatitis. Six patients were enrolled at dose level 0 (nab-paclitaxel 40 mg/m(2)) with no DLTs. Nine of 10 evaluable patients had a partial response.Concurrent chemoradiotherapy with nab-paclitaxel 40 mg/m(2) and carboplatin AUC 2 is a safe and well-tolerated therapeutic regimen in patients with stage III NSCLC. A separate phase I/II study to evaluate the efficacy of this regimen is under way.
| S-EPMC4425395 | biostudies-literature