Resected Stage IB Non-small Cell Lung Cancer Research Articles

Influence of adjuvant chemotherapy on survival for patients with completely resected high-risk stage IB NSCLC

BackgroundThe use of adjuvant chemotherapy (ACT) in completely resected stage IB NSCLC is still controversial. This study aims to investigate the efficacy of ACT in pathological stage IB non-small cell lung cancer (NSCLC) with high risk factors.MethodsPatients with pT2aN0M0 stage IB NSCLC who underwent complete resection from 2013 to 2017 were retrospectively analyzed. Univariate and multivariable logistic regression analysis was used to assess potential independent risk factors associated with poor prognosis. To compare survival between patients who received ACT and those who did not.ResultsIn univariate and multivariate analyses, adenocarcinomas with predominantly micropapillary (MIP) and solid patterns (SOL), poorly differentiated squamous cell carcinoma (SCC), number of lymph nodes dissected less than 16 and tumor size larger than 36 mm were identified as high-risk factors for recurrence. In patients with high risk factors for recurrence, ACT resulted in significantly longer DFS (HR, 0.4689, 95%CI, 1.193–3.818; p = 0.0108) and OS (HR, 0.4696, 95%CI, 0.6578–6.895; p = 0.2073), although OS failed to reach statistically significance. After propensity score matching (PSM), 67 pairs of patients were 1:1 matched in the two groups and all baseline characteristics were well balanced. The results also demonstrated that ACT was associated with improved DFS (HR, 0.4776, 95%CI, 0.9779–4.484; p = 0.0440) while OS was not significantly different (92.5% vs. 91.0%; HR, 0.6167, 95%CI, 0.1688–2.038; p = 0.7458). In patients with low-risk factors for recurrence, DFS (HR, 0.4831, 95%CI, 0.03025-7.715; p = 0.6068) and OS (HR, 0.969, 95%CI, 0.08364-11.21; p = 0.9794) was not significantly different between those who received ACT and those who did not.ConclusionIn patients with completely resected stage IB NSCLC, ACT can improve survival in patients with high risk for recurrence. Further large multicenter studies are needed to confirm these findings.

Surgically Treated pT2aN0M0 (Stage IB) Non-Small Cell Lung Cancer: A 20-Year Single-Center Retrospective Study

Introduction The suitability of adjuvant therapy (AT) in patients with stage IB non-small cell lung cancer (NSCLC) is still under debate considering the cost-benefit ratio between improvement in survival and side effects. We retrospectively evaluated survival and incidence of recurrence in radically resected stage IB NSCLC, to determine whether AT could significantly improve prognosis. Methods Between 1998 and 2020, 4692 consecutive patients underwent lobectomy and systematic lymphadenectomy for NSCLC. Two hundred nineteen patients were pathological T2aN0M0 (>3 and ≤4 cm) NSCLC 8th TNM. None received preoperative or AT. Overall survival (OS), cancer specific survival (CSS) and the cumulative incidence of relapse were plotted and log-rank or Gray's tests were used to assess the difference in outcome between groups. Results The most frequent histology was adenocarcinoma (66.7%). Median OS was 146 months. The 5-, 10-, and 15-year OS rates were 79%, 60%, and 47%, whereas the 5-, 10-, and 15-year CSS were 88%, 85%, and 83%, respectively. OS was significantly related to age (p < 0.001) and cardiovascular comorbidities (p = 0.04), whereas number of LNs removed was an independent prognostic factor of CSS (p = 0.02). Cumulative incidence of relapse at 5-, 10-, and 15-year were 23%, 31%, and 32%, respectively, and significantly related to the number of LNs removed (p = 0.01). Patients with more than 20 LNs removed and clinical stage I had a significantly lower relapse (p = 0.02). Conclusions Excellent CSS, up to 83% at 15-year, and relatively low risk of recurrence for stage IB NSCLC (8th TNM) patients suggested that AT for those patients could be reserved only for very selected high-risk cases.

Adjuvant icotinib versus observation in patients with completely resected, EGFR-mutated, stage IB non–small cell lung cancer (GASTO1003, CORIN): A randomized phase II trial.

8519 Background: The role of adjuvant therapy in patients with completely resected stage IB non-small-cell lung cancer (NSCLC) remains to be determined. Icotinib is standard-of-care therapy for patients with advanced NSCLC harboring epidermal growth factor receptor (EGFR) mutation. This phase II study investigated whether adjuvant therapy with icotinib improves the clinical outcome compared with observation in patients with EGFR mutation-positive resected stage IB NSCLC. Methods: This phase II, open-label, randomized study (GASTO1003, CORIN) was conducted at Sun Yat-sen University Cancer Center. From May 2013 to December 2020, patients with completely resected, EGFR mutation-positive, stage IB (7th TNM staging for NSCLC) NSCLC without adjuvant chemotherapy according to physician and patient choices were enrolled. The patients were assigned in a 1:1 ratio to receive adjuvant therapy with icotinib (125mg, three times daily) for 12 months or to undergo observation. Therapy continued until disease progression or intolerable toxicity. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. Survival endpoints were assessed in the intention-to-treat population. Results: Three patients withdrew consent and were excluded. A total of 128 patients were enrolled and randomized, with 63 patients in the icotinib group and 65 patients in the observation group. Baseline characteristics were well balanced between the groups. The median duration of follow-up was 34.9 months. A total of 13 recurrence events occurred, including 2 in the icotinib arm and 11 in the observation arm. DFS was significantly longer among those in the icotinib arm than among those in the observation arm (hazard ratio: 0.20, 95% confidence interval, 0.04-0.89; P = 0.018). The 3-year DFS for the icotinib and observation arms were 95.3% and 86.7%, respectively. The OS data were immature with 3 deaths in the observation arm. The safety profile was consistent with the known safety profile of icotinib. Icotinib was well tolerated with no unexpected adverse events. No treatment-related death occurred. Conclusions: Adjuvant icotinib shows prolonged DFS and acceptable toxicity in patients with completely resected EGFR-mutated stage IB NSCLC. Ajuvant icotinib provides a treatment option for these patients. Clinical trial information: NCT02264210.

Effect of Adjuvant Chemotherapy on Survival of Patients With 8th Edition Stage IB Non-Small Cell Lung Cancer.

BackgroundThe efficacy of adjuvant chemotherapy in patients with 8th edition stage IB (tumor size ≤4 cm) non-small cell lung cancer (NSCLC) remains unclear.MethodsWe identified 9757 eligible patients (non-chemotherapy group: n=8303; chemotherapy group: n=1454) between 2004 and 2016 from the Surveillance, Epidemiology and End Results (SEER) database. Log-rank test was used to compare overall survival (OS) between the chemotherapy and non-chemotherapy groups. Cox regression model was applied to investigate the independent prognosis factors of all surgically treated stage IB patients, and then the nomogram was constructed. Propensity score matching (PSM) was performed to reduce the confounding bias, and subgroup analyses of the matched cohort were also performed. Finally, we reviewed 184 patients with stage IB NSCLC from July 2008 to December 2016 in Jinling Hospital as a validation cohort, and compared disease-free survival (DFS) and OS between the two groups.ResultsIn the SEER database cohort, adjuvant chemotherapy was associated with improved OS in both unmatched and matched (1417 pairs) cohorts (all P <0.05). The survival benefit (both OS and DFS) was confirmed in the validation cohort (P <0.05). Multivariate analysis showed age, race, sex, marital status, histology, tumor location, tumor size, differentiation, surgical method, lymph nodes (LNs) examined, radiotherapy and chemotherapy were prognostic factors for resected stage IB NSCLC (all P <0.05). The concordance index and calibration curves demonstrated good prediction effect. Subgroup analyses showed patients with the following characteristics benefited from chemotherapy: old age, poor differentiation to undifferentiation, 0-15 LNs examined, visceral pleural invasion (VPI), lobectomy and no radiotherapy (all P <0.05).ConclusionsAdjuvant chemotherapy is associated with improved survival in 8th edition stage IB NSCLC patients, especially in those with old age, poorly differentiated to undifferentiated tumors, 0-15 LNs examined, VPI, lobotomy and no radiotherapy. Further prospective trials are needed to confirm these conclusions. Besides, the nomogram provides relatively accurate prediction for the prognosis of resected stage IB NSCLC patients.

Adjuvant chemotherapy for surgically resected non–small cell lung cancer

Despite surgical resection, patients with early-stage (I to IIIA) non-small cell lung cancer (NSCLC) are at considerable risk of recurrence and death from their lung cancer. In recent years, multiple, large, randomized trials assessing the efficacy of adjuvant chemotherapy for resected NSCLC have been reported. Three of 6 trials with 300 or more patients with early-stage NSCLC have demonstrated that adjuvant cisplatin-based chemotherapy can significantly improve 5-year survival in carefully selected patients with resected NSCLC. These benefits have been confirmed in a meta-analysis of modern cisplatin-based adjuvant trials. The most consistent benefit has been reported in patients with resected stage II and IIIA NSCLC. The benefit of adjuvant chemotherapy in patients with resected stage IB NSCLC is less concrete. Herein, we review the results of the major adjuvant chemotherapy trials and their implications for the treatment of patients with completely resected NSCLC. A future challenge will be to identify the subsets of patients who will derive the greatest benefit from adjuvant chemotherapy. Current trials are also underway to define the role of novel targeted therapies, such as inhibitors of the epidermal growth factor receptor and monoclonal antibodies, in adjuvant treatment strategies.

Adjuvant chemotherapy (AC) in stage IB non-small cell lung cancer (NSCLC): Long-term follow-up of Cancer and Leukemia Group B (CALGB) 9633.

7015 Background: The value of AC in stage IB NSCLC remains controversial. In 2004, preliminary results of CALGB 9633 demonstrated a statistically significant overall survival (OS) advantage for pts randomized to adjuvant paclitaxel and carboplatin in resected stage IB NSCLC. However, subsequent analyses failed to demonstrate a significant OS advantage for all pts, although an unplanned subset analysis did show improved OS in pts with tumor diameter ≥4 cm (JCO, 26:5043, 2008). This report provides updated OS for CALGB 9633. Moreover, because the new 2010 AJCC staging system does not recognize 4 cm as a cut point, we correlated results with subgroups incorporated in the new system. Methods: Resected stage IB pts were randomized to paclitaxel 200 mg/m2 and carboplatin AUC 6 q3wks X4 cycles or observation. OS was the primary endpoint. Because of slow accrual, the accrual target was reduced from 500 to 384 pts, providing 80% power using a 1-tail logrank with alpha=0.05. Results: Between 1996-2003, 344 pts were randomized. Median follow-up is 9 yrs. There are now 197 deaths. While the study remains negative, there is a powerful trend toward improved OS for all pts (HR=0.80; 90% CI 0.63-1.02; p=0.062, 1-tail), with a 7% advantage in 8 yr OS favoring AC (51% vs. 44%; p=0.087); median OS is 8.2/6.6 yrs in chemo/control groups. Subgroup analysis using a 4 cm cut-off continues to show a strong OS signal favoring AC for those with large tumors. In pts with tumors ≥4 cm, the HR for OS is 0.77 (90% CI: 0.57-1.04; p=0.079); there is a 10% improvement in 8 yr OS (53% vs.43%; p=0.059); median OS is 8.9/6.6 yrs in chemo/control groups. In pts with tumors <4cm there is little OS difference (HR=0.89; p=0.31). While correlations with the new staging system yield inconclusive findings due to small sample size, it does show that larger tumors derive greater benefit from AC. For example, in 43 pts with tumors >7 cm (defined as T3 in the new AJCC system), the HR for OS was 0.53 (90% CI: 0.28-1.00; p=0.051). Conclusions: While not statistically significant, long term follow-up of this underpowered study shows a strong OS signal for all pts and for pts with tumors ≥4m. Our long-term data justifies AC in resected node negative NSCLC ≥4 cm in diameter.

Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): Update of Cancer and Leukemia Group B (CALGB) protocol 9633

7007 Background: In 2004, preliminary results of CALGB 9633 demonstrated statistically significant evidence that adjuvant chemotherapy with paclitaxel and carboplatin (PC) improved disease-free (DFS) and overall survival (OS) in resected stage IB NSCLC. Indeed, the study was closed early by the DSMB after a planned interim analysis demonstrated a p value for OS less than a prespecified stopping boundary. However, two larger trials, NCIC-JBR10 and ANITA, have shown significant OS advantages with adjuvant chemo, but failed to demonstrate improved survival in the stage IB subset. This report provides more mature data from CALGB 9633. Methods: InCALGB 9633, stage IB patients (pts) were randomized following resection to paclitaxel 200 mg/m2 and carboplatin AUC 6 q3wks ×4 cycles or to observation. While initially planned to accrue 500 pts, the accrual rate was &lt;50% of expected. Because slow accrual allowed longer observation times for each pt, the accrual target was reduced to 384 pts. OS is the primary endpoint. The redesigned study had 80% power to detect a hazard ratio (HR) of 0.67 after 150 observed deaths using a 1-tailed logrank test conducted at the 0.05 level of significance. Results: Between 9/15/96 and 11/26/03, 344 pts were randomized. Median follow-up is 54 mo. Demographics and toxicity has been previously reported (JCO Sup, 22:621a, 2004). The current intent-to-treat analysis shows a significant improvement in DFS favoring adjuvant chemo (HR=0.74; 90% 2-sided CI: 0.57–0.96; p=0.027). There is a trend toward improvement in OS that is not significant (HR=0.80; 90% CI: 0.60–1.07; p=0.10). There is, however, a significant advantage in 3-yr survival (79% vs. 70%; p=0.045). Five-yr survival is not different (60% vs. 57%; p=0.32), although median follow-up is &lt;5 yrs and CIs are wide. Continued follow-up is planned since only 131 of 150 deaths required for final analysis have been observed. Conclusions: This updated but “preliminary” analysis no longer shows a significant OS advantage for adjuvant chemotherapy in stage IB NSCLC. However, the re-designed study does not have adequate power to detect small differences in OS that may be clinically significant. Advantages in DFS and 3-yr survival support continued consideration of adjuvant PC in stage IB NSCLC. [Table: see text]