Durvalumab for non-resectable stage IIIB non-small cell lung cancer-a small step or a big leap?
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ABSTRACT:
SUBMITTER: Dempke WCM
PROVIDER: S-EPMC5943223 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundA small proportion of patients with non-small cell lung cancer (NSCLC) experience objective clinical benefit after neoadjuvant programmed cell death 1 (PD-1) blockade. A neoadjuvant therapeutic regimen combining immune checkpoint blockade with chemotherapy might improve the treatment effect, but such a regimen has not been tested in patients with resectable stage IIIA/IIIB NSCLC.MethodsA retrospective study of 35 patients with resectable stage IIIA and IIIB NSCLC who were treated with neoadjuvant chemoimmunotherapy (NCIO) was performed. Patients were evaluated for pathological complete response (pCR), major pathologic response (MPR), safety, and feasibility. The correlations of pathologic response with various clinical factors were studied to identify predictors of pathological response.ResultsNCIO was associated with few immediate adverse events. NCIO did not delay planned surgery and led to a pCR rate of 51.43% and an MPR rate of 74.29% for the primary tumor. No association was observed between programmed death-ligand 1 (PD-L1) expression before NCIO and the pathologic response (Pearson's r=-0.071; P=0.685). However, a significant difference was observed in pathological response in patients with intracavitary and extracavitary tumors (P<0.05). Patients with intracavitary type had a higher pCR (76.47% vs. 31.58%) and MPR (100% vs. 50.00%) rate than patients with extracavitary type (Pearson's r=0.7280; P=0.0009).ConclusionsNCIO was associated with few side effects, did not delay surgery, and achieved a pCR in 51.43% and MPR in 74.29% of resected tumors. No significant correlation was found between pathologic response and PD-L1 expression. While the intracavitary and extracavitary tumors type T was predictive of the pathological response to NCIO.
| S-EPMC8182703 | biostudies-literature
Project description: Not available
| S-EPMC5949420 | biostudies-literature
Project description: Not available
| S-EPMC5949435 | biostudies-literature
Project description:Approximately one third of patients with non-small cell lung cancer have unresectable stage IIIA or stage IIIB disease, and appropriate patients are candidates for chemoradiotherapy with curative intent. The optimal treatment paradigm is currently undefined. Concurrent chemoradiotherapy, compared with sequential chemotherapy and thoracic radiation therapy (TRT), results in superior overall survival outcomes as a result of better locoregional control. Recent trials have revealed efficacy for newer chemotherapy combinations similar to that of older chemotherapy combinations with concurrent TRT and a lower rate of some toxicities. Ongoing phase III trials will determine the roles of cisplatin and pemetrexed concurrent with TRT in patients with nonsquamous histology, cetuximab, and the L-BLP25 vaccine. It is unlikely that bevacizumab will have a role in stage III disease because of its toxicity. Erlotinib, gefitinib, and crizotinib have not been evaluated in stage III patients selected based on molecular characteristics. The preliminary results of a phase III trial that compared conventionally fractionated standard-dose TRT (60 Gy) with high-dose TRT (74 Gy) revealed an inferior survival outcome among patients assigned to the high-dose arm. Hyperfractionation was investigated previously with promising results, but adoption has been limited because of logistical considerations. More recent trials have investigated hypofractionated TRT in chemoradiotherapy. Advances in tumor targeting and radiation treatment planning have made this approach more feasible and reduced the risk for normal tissue toxicity. Adaptive radiotherapy uses changes in tumor volume to adjust the TRT treatment plan during therapy, and trials using this strategy are ongoing. Ongoing trials with proton therapy will provide initial efficacy and safety data.
| S-EPMC3360908 | biostudies-literature
Project description:Currently, chemotherapy is the standard adjuvant treatment for early-stage non-small cell lung cancer (NSCLC). However, adjuvant cisplatin-based chemotherapy after surgery has been shown to improve 5-year survival rates by only 4-5%. Immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced NSCLC, there is a growing interest in the role of immunotherapy in early-stage NSCLC. Here, we summarize the rationale for adjuvant immunotherapy, including the postoperative immunosuppressive environment and immunological effects of platinum chemotherapy. Many ongoing clinical trials and the related progress in adjuvant immunotherapy in early-stage resectable NSCLC are discussed. Furthermore, we highlight several unresolved challenges, including markers predictive of treatment benefit, the efficacy of treatment for some oncogene-addicted tumors, the optimal combination therapy, the duration of adjuvant immunotherapy, and optimal selection between neoadjuvant and adjuvant immunotherapy. Early findings in some clinical trials are promising, and updated overall survival results will be useful for validating the current role of adjuvant immunotherapy, particularly in the context of perioperative strategy.
| S-EPMC9909200 | biostudies-literature
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:BackgroundResearches on programmed cell death (PD-1) as neoadjuvant immunotherapy for resectable non-small cell lung cancer is underway, which brings hope for individuals with the disease. However, a study dedicated to lung squamous cell carcinoma (LUSC) specifically has yet to be conducted. Now, data from our pilot prospective research neoadjuvant study provide new insights in the field of neoadjuvant regimen for LUSC.MethodsBetween June 2019 and July 2020, 37 adults with untreated, surgically resectable stage IIB-IIIB LUSC were enrolled into this prospective study. Patients received 2 cycles of pembrolizumab (2 mg/kg) with chemotherapy (albumin-bound paclitaxel 100 mg/m2 on days 1 and 8 + carboplatin AUC 5) via intravenous administration every 3 weeks, and underwent surgical treatment 3-4 weeks after the second cycle. The primary endpoint of the study was the tumor pathologic complete response (pCR) rate. The toxicity profile, tumor major pathological remission, complete resection rate, response rate, and operative and postoperative complications were also evaluated.ResultsThe postoperative pathological specimens of 17 (45.9%) patients suggested pCR. Neoadjuvant pembrolizumab with chemotherapy had an acceptable side-effect profile, and no patients withdrew from the study preoperatively due to disease progression or toxicity. A major pathological response occurred in 24 (64.9%) resected tumors. All tumors were completely resected (R0, 100%). According to the Response Evaluation Criteria in Solid Tumors (RESIST), a response was evaluated before surgery in 32 (86.5%) patients by computed tomography. Twenty-five (67.6%) patients underwent thoracoscopic surgery. No deaths or postoperative major complications requiring reoperation occurred. Recurrence or metastasis was found in 2 patients during follow-up of 2-14 months.ConclusionsThe early outcomes of pembrolizumab with chemotherapy in the neoadjuvant setting as a novel treatment for resectable stage IIB-IIIB LUSC showed a high pCR rate that has not been seen previously, as well as a high R0 resection rate and a low toxicity profile. The long-term efficacy of this novel treatment and the validity of the present findings should be confirmed with longer follow-up and prospective comparative trials.
| S-EPMC8024839 | biostudies-literature
Project description:BackgroundDurvalumab consolidation is associated with improved survival following concurrent chemoradiotherapy (CCRT) in patients with stage III non-small cell lung cancer (NSCLC). Given the heterogeneity of stage III NSCLC patients, in this study we evaluated the efficacy and safety of durvalumab in the real-world setting.MethodUnresectable stage III NSCLC patients were retrospectively studied: one cohort received CCRT, another had CCRT-durvalumab. Primary endpoints were progression-free survival (PFS) and overall survival (OS), secondary endpoints were relapse rate and safety. In CCRT-durvalumab cohort, association between blood markers with survival and pneumonitis risk were analyzed.ResultsA total of 84 patients were enrolled: 45 received CCRT, and 39 received CCRT-durvalumab. Median PFS was 17.5 months for CCRT-durvalumab and 8.9 months for CCRT-alone (HR 0.47, p = 0.038). Median OS was not-reached for CCRT-durvalumab and 22.3 months for CCRT-alone (HR 0.35, p = 0.024). Both EGFR-positive and wild-type (WT) patients had numerically improved PFS with durvalumab consolidation compared to CCRT-alone, 17.5 versus 10.9 months and 11.8 versus 6.63 months, respectively (interaction p-value = 0.608). Grade 2+ pneumonitis was detected in 25% of patients in the durvalumab cohort. Most pneumonitis occurred at 3.5 weeks after durvalumab initiation. Baseline neutrophil-to-lymphocyte ratio (NLR) ≥ 3 and ≥5 were associated with shorter PFS with durvalumab. Week 6 platelet-lymphocyte-ratio ≥ 180 was associated with a lower risk of pneumonitis.ConclusionIn this real-world study, durvalumab consolidation post CCRT was associated with a statistically significant improvement in PFS and OS. Effect of durvalumab on PFS was not modified by EGFR status. Active surveillance for pneumonitis is crucial. Baseline NLR may help to predict the benefit of treatment with durvalumab.
| S-EPMC9663681 | biostudies-literature
Project description:ImportanceThe benefit of neoadjuvant camrelizumab plus chemotherapy for resectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) remains unknown.ObjectiveTo assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy vs chemotherapy alone for patients with resectable stage IIIA or IIIB NSCLC.Design, setting, and participantsIn this randomized phase 2 clinical trial conducted at 2 hospitals in China, patients aged 18 to 70 years with resectable stage IIIA or IIIB (T3N2) NSCLC were enrolled between April 7, 2020, and January 12, 2022.InterventionsPatients were randomly assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m2, and platinum [cisplatin, 75 mg/m2; carboplatin, area under the curve, 5; or nedaplatin, 100 mg/m2]) or chemotherapy alone, followed by surgery after 4 to 6 weeks.Main outcomes and measuresThe primary end point was the pathologic complete response (pCR) rate. Secondary end points included the major pathologic response (MPR) rate, objective response rate (ORR), event-free survival (EFS), and safety. Disease-free survival (DFS, defined as the time from surgery to disease recurrence or death from any cause) was analyzed post hoc. Efficacy was assessed on a modified intention-to-treat basis.ResultsNinety-four Chinese patients were randomized, and 88 (93.6%; median age, 61 years [IQR, 54-65 years]; 74 men [84.1%]) received allocated neoadjuvant treatment (43 received camrelizumab plus chemotherapy, and 45 received chemotherapy alone). Among these 88 patients, the pCR rate was 32.6% (14 of 43; 95% CI, 19.1%-48.5%) with camrelizumab plus chemotherapy vs 8.9% (4 of 45; 95% CI, 2.5%-21.2%) with chemotherapy alone (odds ratio, 4.95; 95% CI, 1.35-22.37; P = .008). The MPR rates were 65.1% (95% CI, 49.1%-79.0%) with camrelizumab plus chemotherapy and 15.6% (95% CI, 6.5%-29.5%) with chemotherapy alone. The radiographic ORRs were 72.1% (95% CI, 56.3%-84.7%) with camrelizumab plus chemotherapy and 53.3% (95% CI, 37.9%-68.3%) with chemotherapy alone. With a median follow-up of 14.1 months (IQR, 9.2-20.9 months), the median EFS and DFS were not reached in either group. The most common neoadjuvant treatment-related adverse events of grade 3 or higher were decreased white blood cell count (6 of 43 [14.0%] in the camrelizumab plus chemotherapy group vs 2 of 45 [4.4%] in the chemotherapy group) and decreased neutrophil count (3 of 43 [7.0%] in the camrelizumab plus chemotherapy group vs 5 of 45 [11.1%] in the chemotherapy group). No treatment-related deaths were reported.Conclusions and relevanceThis randomized clinical trial found that among patients with resectable stage IIIA or IIIB (T3N2) NSCLC, camrelizumab plus chemotherapy, compared with chemotherapy alone, significantly improved the pCR rate with manageable toxic effects.Trial registrationClinicalTrials.gov Identifier: NCT04338620.
| S-EPMC10401395 | biostudies-literature
Project description:We present a case of a 43-year-old female patient with clinical stage IIIB (T3N2M0) anaplastic lymphoma kinase (ALK)-positive adenocarcinoma of the lung. Surgery was not performed initially because of multiple mediastinal lymph nodes invasion, although the mass was technically resected. With the assessment of upfront multidisciplinary consultation, administration of neoadjuvant crizotinib was selected to induce the downstaging and facilitate the subsequent surgical treatment. After 10 weeks of neoadjuvant crizotinib treatment, a partial response was achieved and the tumor could be radically resected. There were no sever toxic effects and treatment-related surgical delay during the whole neoadjuvant crizotinib therapy. The patient then successfully underwent video-assisted single port thoracoscopic right upper lobectomy and lymphadenectomy. Concurrent chemotherapy and radiotherapy were applied postoperatively. Perioperative targeted therapy demonstrated good curative effect in this case, and no recurrence was observed at the clinic 8 months after surgery. In this case, the safety and effectiveness of neoadjuvant crizotinib and subsequent surgery are preliminarily proved. We here intend to investigate the optimal setting of neoadjuvant targeted therapy combined with minimally invasive surgery and postoperative adjuvant therapy, inspire more potential targeted treatment based schedules and to apply these strategies in treating patients with locally advanced mutant-positive non-small cell lung cancer (NSCLC).
| S-EPMC7333158 | biostudies-literature