Adjuvant chemotherapy or immunotherapy for completely resected stage IB non-small cell lung cancer: still a grey zone?
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ABSTRACT:
SUBMITTER: Lee KY
PROVIDER: S-EPMC10087986 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
Publications
Adjuvant chemotherapy or immunotherapy for completely resected stage IB non-small cell lung cancer: still a grey zone?
Lee Kuan-Yu KY Hsu Chen-Xiong CX
Translational lung cancer research 20230301 3
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Project description:Surgery is regarded as the primary treatment modality for early stage non-small cell lung cancer (NSCLC), but even after complete resection, a substantial percentage of these patients eventually develop local recurrence or distant metastases. Therefore more effective treatment strategies to reduce lung cancer mortality and recurrence rate are needed. Only recently has the use of adjuvant chemotherapy become standard in early stage NSCLC, at least for stage II and resected IIIA NSCLC. Controversies remain about the benefit for stage I patients. Five-year survival improvements of 5% to 10% have been reported with cisplatin-based adjuvant chemotherapy from multiple large randomized phase III clinical trials and meta-analyses. Questions remain as to which patients benefit and which regimens are best. In this paper, important clinical research in the field of adjuvant chemotherapy of NSCLC is reviewed.
| S-EPMC4367729 | biostudies-literature
Project description:We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). We also examined the relation between DNA ploidy pattern and the response to chemotherapy. A total of 267 patients with NSCLC (pathologically documented stage I, II, or IIIA) underwent complete resection, and DNA ploidy pattern was analysed. Patients with stage I disease (n=172) were randomly assigned to receive surgery alone (group A) or surgery followed by adjuvant chemotherapy (UFT (oral anti-cancer drug, a combination of Uracil and Tegaful) 400 mg day-1 for 1 year after surgery; group B). Stage II or IIIA disease patients (n=95) were randomly assigned to surgery alone (group C) or surgery followed by chemotherapy (two 28-day courses of cisplatin 80 mg m-2 on day 1 plus vindesine 3 mg m-2 on days 1 and 8, followed by UFT 400 mg day-1 for at least 1 year; group D). Eight-year overall survival rate in patients with stage I disease was 74.2% (95% confidence interval (CI): 64.4-84.0%) in group B and 57.6% (95% CI: 46.4-68.8%) in group A (P=0.045 by log-rank test). In patients with stage II and IIIA disease, no difference was found between groups C and D. Analysis according to DNA ploidy pattern revealed no difference between the groups. Postoperative chemotherapy with UFT was suggested to be useful in patients with completely resected stage I NSCLC. No difference was seen in relation to DNA pattern in any treatment group.
| S-EPMC2360551 | biostudies-other
Project description:BackgroundPrognostic biomarker, which can inform the treatment outcome of adjuvant chemotherapy (ACT) after complete resection of early-stage non-small cell lung cancer (NSCLC), is urgently needed for the personalized treatment of these patients.Patients and methodsThe prognostic value of gene expression of the estrogen receptor (ER) on the effect of ACT in completely resected NSCLC was investigated in the present study. Two independent datasets from Gene Expression Omnibus (GEO) with a total of 309 patients were included in this study. The prognostic value of ER gene expression on ACT's efficacy was evaluated by survival analysis and Cox hazards models.ResultsWe found a consistent and significant prognostic value of ERβ (ESR2) expression for ACT's efficacy in completely resected NSCLC in both of the two independent cohorts. After multivariate adjustment, a significant survival benefit of ACT was observed in patients with low expression of ESR2, with a hazard ratio (HR) of 0.19 (95%CI 0.05-0.82, p = 0.026) in the discovery cohort and an HR of 0.27 (95%CI 0.10-0.76, p = 0.012) in the validation group. No significant benefit of ACT in the subgroup of patients with high expression of ESR2 was observed, with an HR of 0.80 (95%CI 0.31-2.09, p = 0.644) in the discovery cohort and an HR of 1.05 (95%CI 0.48-2.29, p = 0.896) in the validation group.ConclusionA significant survival benefit from ACT was observed in patients with low ESR2 expression. No significant survival benefit was observed in patients with high ESR2 expression. Detection of ESR2 expression in NSCLC may help personalize its treatment after complete resection.
| S-EPMC7746143 | biostudies-literature
Project description:BACKGROUND:The use of adjuvant chemotherapy (ACT) for stage IB lung adenocarcinoma remains controversial. We examined the benefits of ACT in stage IB patients with tumors composed of solid material. METHODS:The records of 309 patients with stage IB lung adenocarcinoma who had undergone complete resection between 2006 and 2015 were reviewed. All pathological slides were evaluated for the composition of solid material. RESULTS:Our data showed that although disease-free survival (DFS) and overall survival (OS) were not significantly different (P = 0.306 and P = 0.061, respectively) between patients displaying a solid pattern of tumor growth and treated with or without ACT, patients with a solid predominant pattern of tumor growth treated with ACT had longer DFS (hazard ratio 0.359; P = 0.033) and OS (hazard ratio 0.205; P = 0.003). In patients with solid non-predominant patterns, treatment with ACT had no effect on DFS (P = 0.326) or OS (P = 0.508). CONCLUSIONS:Postoperative patients with the solid predominant pattern of stage IB lung adenocarcinoma may benefit from ACT, while those with the solid non-predominant pattern will not.
| S-EPMC6360240 | biostudies-literature
Project description:BackgroundThis phase 2 trial aimed to compare adjuvant icotinib with observation in patients with epidermal growth factor receptor (EGFR) mutation-positive resected stage IB non-small cell lung cancer (NSCLC).MethodsWe performed a randomised, open-label, phase 2 trial from May 1, 2015 to December 29, 2020 at Sun Yat-sen University Cancer Center in China. Patients with completely resected, EGFR-mutant, stage IB (the 7th edition of TNM staging) NSCLC without adjuvant chemotherapy were randomised (1:1) to receive adjuvant therapy with icotinib (125 mg, three times daily) for 12 months or to undergo observation until disease progression or intolerable toxicity occurred. The primary endpoint was 3-year disease-free survival (DFS). CORIN (GASTO1003) was registered with Clinicaltrials.gov, with the number NCT02264210.FindingsA total of 128 patients were randomised, with 63 patients in the icotinib group and 65 patients in the observation group. The median duration of follow-up was 39.9 months. The three-year DFS was significantly higher in the icotinib group (96.1%, 95% confidence interval [CI], 91.3-99.9) than in the observation group (84.0%, 95% CI, 75.1-92.9; P = 0.041). The DFS was significantly longer in the icotinib group than in the observation group, with a hazard ratio (HR) of 0.23 (95% CI, 0.07-0.81; P = 0.013). The OS data were immature, with three deaths in the observation arm. In the icotinib group, adverse events (AEs) of any grade were reported in 49 patients (77.8%), and grade 3 or greater AEs occurred in four patients (6.3%). No treatment-related deaths occurred.InterpretationOur findings suggested that adjuvant icotinib improved the 3-year DFS in patients with completely resected EGFR-mutated stage IB NSCLC with a manageable safety profile.FundingThis study was sponsored by Betta Pharmaceutical Co., Ltd.
| S-EPMC9932314 | biostudies-literature
Project description:BackgroundWe aimed to evaluate the efficacy of postoperative adjuvant pemetrexed plus cisplatin (Pem-Cis) in pathologic stage IB-IIIA lung adenocarcinoma (LUAD) patients.MethodsA prospective, phase II study was performed in seven institutions in South Korea. Patients with completely resected stage IB-IIIA LUAD received pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2). Adjuvant treatments were administered every 3 weeks for 4 cycles. The primary endpoint was to prove the Pem-Cis's superiority in terms of 2-year disease-free survival rate (DFSR) compared with historical control without adjuvant chemotherapy (50%).ResultsBetween August 2015 and February 2018, 105 patients were enrolled in this study. Approximately 31.4% (n=33), 43.8% (n=46), and 24.8% (n=26) of patients had pathologic stage IB, II, and IIIA, respectively. Most of the patients underwent lobectomy (n=98, 93.3%). Moreover, 41.1% and 12.1% of the patients had epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase rearrangement. Four cycles of Pem-Cis were administered in 99 patients (94.3%). At a median follow-up of 57.7 months, the 2-year DFSR was 78.1%. Multivariable analysis showed that pathologic stage IIIA and EGFR mutation were significant risk factors for DFS. Grade 3 adverse events occurred in 10 patients (9.5%), and leukopenia (n=3, 2.9%) was the most common adverse event.ConclusionsAdjuvant Pem-Cis is superior to historical control without adjuvant treatment in terms of 2-year DFSR; the proportion of patients with stage IB and driver mutations were higher than that of patients in previous trials. Pem-Cis showed favorable tolerability as adjuvant chemotherapy (clinicaltrial.gov; Identifier: NCT02498860).
| S-EPMC9459613 | biostudies-literature
Project description:In patients with completely resected non-small cell lung cancer (NSCLC), postoperative adjuvant chemotherapy has been associated with improvement in survival by minimizing the risk of recurrence. For years, systemic chemotherapy including platinum based regimen has been a mainstay treatment modality of adjuvant treatment after complete resection. ADAURA study showed that among completely resected IB to IIIA NSCLC, disease-free survival was significantly better in patients under adjuvant osimertinib than a placebo group. After the advent of a variety of new treatment regimens, such as third generation TKI and immunotherapy, the landscape of postoperative adjuvant treatment has been changing. In this review, we discuss some key issues regarding choice of adjuvant treatment after complete resection in NSCLC, and provide further updates on recent advances in treatment modalities.
| S-EPMC8807337 | biostudies-literature
Project description:ObjectiveTo examine the effectiveness of systemic chemotherapy following radical hysterectomy for women with intermediate-risk stage IB cervical cancer.Materials and methodsThis is a retrospective analysis of a previously organized nation-wide cohort study examining 6,003 women with stage IB-IIB cervical cancer who underwent radical hysterectomy between 2004 and 2008 in Japan. Survival of 555 women with stage IB cervical cancer in the intermediate-risk group (deep stromal invasion > 50%, large tumor size > 4 cm, and lympho-vascular space invasion [LVSI]) were examined based on adjuvant therapy patterns: chemotherapy alone (n = 223, 40.2%), concurrent chemo-radiotherapy (n = 172, 31.0%), and radiotherapy alone (n = 160, 28.8%).ResultsThe most common intermediate-risk pattern was LVSI with deep stromal invasion (n = 216, 38.5%). The most common chemotherapeutic choice was taxane/platinum (52.2%). Women with adenocarcinoma/adenosquamous histology were more likely to receive chemotherapy (P = 0.03), and intermediate-risk pattern was not associated with chemotherapy use (P = 0.11). Women who received systemic chemotherapy had disease-free survival (5-year rate, 88.1% versus 90.2%, adjusted-hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.52-1.83, P = 0.94) and cause-specific survival (95.4% versus 94.8%, adjusted-HR 0.85, 95% CI 0.34-2.07, P = 0.71) similar to those who received concurrent chemo-radiotherapy on multivariable analysis. Similar results were seen among 329 women with multiple intermediate-risk factors (5-year rates for disease-free survival, chemotherapy versus concurrent chemo-radiotherapy, 87.1% versus 90.2%, P = 0.86; and cause-specific survival 94.6% versus 93.4%, P = 0.82). Cumulative local-recurrence (P = 0.77) and distant-recurrence (P = 0.94) risks were similar across the adjuvant therapy types.ConclusionsOur study suggests that systemic chemotherapy may be an alternative treatment choice for adjuvant therapy in intermediate-risk stage IB cervical cancer.
| S-EPMC5739780 | biostudies-literature
Project description:The global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in patients with resected stage IB-IIIA non-small cell lung cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)-IIIA NSCLC. Upon completing 1-4 cycles of adjuvant cisplatin-based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator-assessed disease-free survival, tested hierarchically first in patients with stage II-IIIA NSCLC whose tumors expressed programmed death-ligand 1 (PD-L1) on ≥1% of tumor cells, then in all randomized patients with stage II-IIIA NSCLC, and finally in the intention-to-treat (ITT) population (stage IB-IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all-randomized stage II-IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD-L1 tumor cells ≥1% stage II-IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease-free survival improvement with atezolizumab vs BSC was observed in the PD-L1 tumor cells ≥1% stage II-IIIA (unstratified hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.25-1.08), all-randomized stage II-IIIA (unstratified HR, 0.62; 95% CI, 0.35-1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34-1.10) populations. Atezolizumab-related grade 3/4 adverse events occurred in 16% of patients; no treatment-related grade 5 events occurred. Adjuvant atezolizumab showed disease-free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.
| S-EPMC9746048 | biostudies-literature
Project description:PurposeTo determine the role and rational application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant therapy in patients with completely resected stage IB-IIIA EGFR-mutant non-small-cell lung cancer (NSCLC).MethodRandomized controlled trials (RCTs) that compared the survival outcomes between adjuvant EGFR-TKIs and adjuvant chemotherapy or a placebo, or between different EGFR-TKI treatment durations for resected NSCLC, were eligible for inclusion. Disease-free survival (DFS) and overall survival (OS) with hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated as effective measures using random-effect or fixed-effect models. Subgroup analysis was also performed.ResultsEleven RCTs involving 2102 EGFR-mutant NSCLC patients with or without EGFR-TKI adjuvant therapy were included. For all stage IB-IIIA NSCLC patients, EGFR-TKIs adjuvant therapy could not only significantly improve DFS (HR 0.43, 95% CI 0.30-0.63, P < 0.001) and 2- and 3-year DFS rates, but also improve OS (HR 0.72, 95% CI, 0.54-0.96, P = 0.024), compared with chemotherapy or the placebo. Further subgroup analyses indicated prolonged OS from first-generation EGFR-TKI adjuvant therapy in stage III patients, compared with chemotherapy or the placebo (HR for OS, 0.34; 95% CI, 0.18-0.63; P = 0.001). Of note, osimertinib adjuvant therapy led to the OS benefit expanding from stage III to stage II-III patients, with significantly improved DFS and a lower risk of brain recurrence, compared with the placebo. A 2-year treatment duration with EGFR-TKI adjuvant therapy showed a significantly lower recurrence risk than a ≤ 1-year duration.ConclusionThe DFS advantage from first-generation EGFR-TKI adjuvant therapy can translate into an OS benefit in stage III NSCLC patients. Osimertinib might be more suitable for adjuvant therapy than first-generation EGFR-TKIs, because of the lower recurrence rate and the potential OS benefit even in early-stage patients. The optimal treatment duration for EGFR-TKIs at different stages of disease needs to be validated.
| S-EPMC10391763 | biostudies-literature