scholarly journals ctDNA Predicts Overall Survival in Patients With NSCLC Treated With PD-L1 Blockade or With Chemotherapy

2021 ◽  
pp. 827-838
Author(s):  
Wei Zou ◽  
Stephanie J. Yaung ◽  
Frederike Fuhlbrück ◽  
Marcus Ballinger ◽  
Eric Peters ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Survival Time ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Median Survival Time ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung

PURPOSE Identification of predictors for overall survival (OS) allows timely detection of clinical efficacy signals and therefore facilitates treatment decisions. We assessed the association between circulating tumor DNA (ctDNA) metrics and the primary end point of OS in a subset of previously treated patients with locally advanced or metastatic non–small-cell lung cancer, who underwent atezolizumab or docetaxel treatment in the open-label randomized phase III OAK trial. MATERIALS AND METHODS Plasma from 94 patients at baseline and at subsequent cycles of therapy every 3 weeks was analyzed retrospectively for ctDNA. ctDNA was measured by allele frequency and mutant molecules per milliliter (MMPM). Concordance between various per-sample metrics and clinical outcome were assessed using C index. RESULTS Of all the ctDNA metrics tested, the association of median MMPM at 6 weeks with OS in patients treated with atezolizumab or docetaxel had a C index > 0.7. The OS hazard ratios relative to high ctDNA above median MMPM within each arm were 0.28 (95% CI, 0.11 to 0.75) for atezolizumab and 0.19 (95% CI, 0.08 to 0.48) for docetaxel. For patients who had ctDNA median MMPM levels of < 4.79, the median survival time was more than 17 months in docetaxel-treated patients and the median survival time was not reached in the atezolizumab-treated patients. CONCLUSION ctDNA MMPM levels measured at 6 weeks post-treatment are associated with OS in advanced non–small-cell lung cancer. Our results suggest that ctDNA has the potential for a noninvasive early liquid biopsy predictor for OS that warrants further studies to demonstrate its utility in clinical development.

scholarly journals Comparative analysis of concurrent and sequential chemoradiation in locally advanced lung cancer: a single institution experience

2019 ◽  
Vol 7 (12) ◽  
pp. 4479
Author(s):  
Shelly Srivastava ◽  
Surendra Kumar Saini ◽  
S. K. Agarwal
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Survival Time ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Median Survival Time ◽  
Concurrent Chemoradiotherapy ◽  
Small Cell ◽  
Small Cell Lung

Background: Outcome of various treatment regimen are dismal in non-small cell lung cancer. This analysis is done to find possible care in authors institutional set up and to see how these protocols have effect in Indian patients in term of toxicity.Methods: Medical records and data on patients who had been diagnosed with non-small cell lung cancer histologically or cytologically, and who had been treated with sequential chemoradiation and concurrent chemoradiation at the hospital from January 2007 to March 2015 was retrospectively reviewed and analyzed. Two groups of sequential chemoradiotherapy and concurrent chemoradiotherapy were formed and compared for outcomes.Results: Of the 114 evaluable patients in sequential chemoradiotherapy group, the median survival time was 16.0 months and the 1, 3- and 5-years overall survival were 57.0, 26.9 and 21.2%, respectively. Median progression free survival (PFS was 13.0 months and the 1, 3 and 5 years PFS were 52.6, 14.6 and 7.8%, respectively. In concurrent chemoradiotherapy group (105 patients), the overall median survival time was 15 months and the 1, 3- and 5-year overall survival were 56.2, 20.6 and 14.7%, respectively. Median PFS was 13 months and the 1, 3 and 5-year PFS were 48.8, 19.7 and 10.3%, respectively. Grade 3 and 4 toxicity in both regimen groups are same and statistically not significant.Conclusions: Analysis confirm dismal outcome with standard treatment and signifies to search for care beyond conventional chemoradiotherapy.

Phase III Trial of Maintenance Gefitinib or Placebo After Concurrent Chemoradiotherapy and Docetaxel Consolidation in Inoperable Stage III Non–Small-Cell Lung Cancer: SWOG S0023

2008 ◽  
Vol 26 (15) ◽  
pp. 2450-2456 ◽  
Author(s):  
Karen Kelly ◽  
Kari Chansky ◽  
Laurie E. Gaspar ◽  
Kathy S. Albain ◽  
James Jett ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Survival Time ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Median Survival Time ◽  
Small Cell ◽  
Phase Iii ◽  
Stage Iii ◽  
Small Cell Lung

PurposeEarly clinical studies with gefitinib showed promising efficacy and mild toxicity in patients with advanced non–small-cell lung cancer (NSCLC). Thus, gefitinib was an ideal agent to evaluate in a maintenance setting in stage III disease.Patients and MethodsUntreated patients with stage III NSCLC, a performance score of 0 to 1, and adequate organ function were eligible. All patients received cisplatin 50 mg/m2on days 1 and 8 plus etoposide 50 mg/m2on days 1 to 5, every 28 days for two cycles with concurrent thoracic radiation (1.8- to 2-Gy fractions per day; total dose, 61 Gy) followed by three cycles of docetaxel 75 mg/m2. Patients whose disease did not progress were randomly assigned to gefitinib 250 mg/d or placebo until disease progression, intolerable toxicity, or the end of 5 years. The planned sample size was 672 patients to confer power of 0.89 to detect a 33% increase over the expected median survival time of 21 months (one-sided P = .025, log-rank test). Random assignment was stratified by stage, histology, and measurable versus nonmeasurable disease.ResultsEnrollment began in July 2001. An unplanned interim analysis conducted in April 2005 rejected the alternative hypothesis of improved survival at the P = .0015 level for 243 randomly assigned patients. The study closed, and preliminary results were reported. Now, with a median follow-up time of 27 months, median survival time was 23 months for gefitinib (n = 118) and 35 months for placebo (n = 125; two-sided P = .013). The toxic death rate was 2% with gefitinib compared with 0% for placebo.ConclusionIn this unselected population, gefitinib did not improve survival. Decreased survival was a result of tumor progression and not gefitinib toxicity.

scholarly journals Value of N1 Lymph Node Examination in the Prognosis of Patients With pT1-3N0M0 Non-Small Cell Lung Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Gaoxiang Wang ◽  
Xianning Wu ◽  
Xiaohui Sun ◽  
Tian Li ◽  
Meiqing Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Survival Time ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Median Survival Time ◽  
Survival Rates ◽  
Small Cell ◽  
Pathological Examination ◽  
Small Cell Lung

ObjectiveThis study aimed to analyze the relationship between the number of examined lymph nodes (ELNs) at the N1 station and the postoperative clinicopathological features and prognosis of patients with pT1-3N0M0 non-small cell lung cancer (NSCLC).MethodsThe cut-off value of the number of ELNs at the N1 station was obtained using X-tile software analysis. Kaplan-Meier survival curve analysis and the Cox proportional hazard model were used to study the impact of the number of ELNs at the N1 station on the prognosis of postoperative patients with pT1-3N0M0 NSCLC.ResultsThe median survival time and 1-, 3- and 5-year survival rates of 0 ELNs at the N1 station were 28.0 months and 74.8%, 45.4%, and 21.2%, respectively. The median survival time and 1-, 3-, and 5-year survival rates of 1–4 ELNs at the N1 station were 45.0 months and 85.5%, 55.4%, and 39.1%, respectively. In the group with ≥ 5 ELNs at the N1 station, the median survival time and the 1-, 3- and 5-year survival rates were 59.0 months and 94.0%, 62.7%, and 48.2%, respectively. Both univariate and multivariate Cox regression analyses showed that the number of ELNs at the N1 station, T stage and operation type were independent factors affecting the prognosis of patients with pT1-3N0M0 NSCLC.ConclusionIncreasing the number of ELNs at the N1 station is positively correlated with the long-term survival rate of patients with T1-3N0M0 NSCLC. At least 5 LNs at the N1 station should be examined in pathological examination.

Randomized Phase IIB Trial of BLP25 Liposome Vaccine in Stage IIIB and IV Non–Small-Cell Lung Cancer

2005 ◽  
Vol 23 (27) ◽  
pp. 6674-6681 ◽  
Author(s):  
Charles Butts ◽  
Nevin Murray ◽  
Andrew Maksymiuk ◽  
Glenwood Goss ◽  
Ernie Marshall ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Survival Time ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Median Survival Time ◽  
Group Performance ◽  
Small Cell ◽  
Stage Iiib ◽  
Small Cell Lung

Purpose To evaluate the effect of BLP25 liposome vaccine (L-BLP25) on survival and toxicity in patients with stage IIIB and IV non–small-cell lung cancer (NSCLC). Secondary objectives included health-related quality of life (QOL) and immune responses elicited by L-BLP25. Patients and Methods Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and stable or responding stage IIIB or IV NSCLC after any first-line chemotherapy were prestratified by stage and randomly assigned to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received a single intravenous dose of cyclophosphamide 300 mg/m2 followed by eight weekly subcutaneous immunizations with L-BLP25 (1,000 μg). Subsequent immunizations were administered at 6-week intervals. Results The survival results indicate a median survival time of 4.4 months longer for patients randomly assigned to the L-BLP25 arm (88 patients) compared with patients assigned to the BSC arm (83 patients; adjusted hazard ratio [HR] = 0.739; 95% CI, 0.509 to 1.073; P = .112). The greatest effect was observed in stage IIIB locoregional (LR) patients, for whom the median survival time for the L-BLP25 arm has not yet been reached compared with 13.3 months for the BSC arm (adjusted HR = 0.524; 95% CI, 0.261 to 1.052; P = .069). No significant toxicity was observed. QOL was maintained longer in patients on the L-BLP25 arm. Conclusion L-BLP25 maintenance therapy in patients with advanced NSCLC is feasible with minimal toxicity. The survival difference of 4.4 months observed with the vaccine did not reach statistical significance. In the subgroup of patients with stage IIIB LR disease, a strong trend in 2-year survival in favor of L-BLP25 was observed.

Moderate Chemo-Radiotherapy in Non-Small Cell Lung Cancer: Results in 21 Patients with Advanced Disease and Low Performance Status

1984 ◽  
Vol 70 (1) ◽  
pp. 81-84 ◽  
Author(s):  
Diego Tummarello ◽  
Emilio Porfiri ◽  
Riccardo Cellerino
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Survival Time ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Median Survival Time ◽  
Performance Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
Low Performance

Twenty-one patients with advanced non-small cell lung cancer and low performance status (Karnofsky: 40–60) were treated with moderate doses of chemo-radiotherapy. Seven patients (33 %) had partial response and a median survival time of 10 months; 5 patients (24 %) had stable disease and a median survival time of 5 months; 9 patients (43 %) had progression of disease and a median survival time of 6 months. Median survival time for the whole group was 7 months. Toxicity related to treatment was minimal and posttreatment performance status was: stable in 10 patients and improved in 5 responsive patients. We conclude that this therapeutic strategy has some efficacy in this category of patients although it failed to show substantial benefit in terms of survival.

scholarly journals The survival impact of concurrent chemotherapy and primary tumor radiotherapy on stage IV squamous non-small-cell lung cancer

2019 ◽  
Author(s):  
Yichao Geng ◽  
Qiu-Ning Zhang ◽  
Yin-Xiang Hu ◽  
Zhu Ma ◽  
Wei-Wei Ouyang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Three Dimensional ◽  
Stage Iv ◽  
Small Cell ◽  
Small Cell Lung

Abstract Objective: To analyse the impact of survival with three-dimensional radiotherapy for stage IV squamous non-small cell lung cancer (NSCLC). Methods: Data for 629 eligible patients who received three-dimensional radiotherapy between 2002 and 2016 were retrospectively analyzed.161 of 183 cases were included pre-protocol. Patients received platinum-doublet chemotherapy with concurrent irradiation of the primary tumour. Primary endpoints were overall survival (OS) and progress-free survival (PFS). Results: Of 161 patients, the 1-, 2-, 3- and 5-year OS rates and median survival time (MST) were 45.7%, 14.1%, 11.2%, 2.2% and 11months, respectively. Using contrastive analysis PTV dose ≥63 Gy and <63 Gy, the 1-, 2-,3- and 5-year overall survival (OS) rates and median survival time (MST)were 48.9% vs 43.3%, 21.8% vs 8.2%, 18.4% vs 4.4%, 5.1% vs 0%, and 12 months vs 11months ( χ 2 = 7.222, P=0.007). Contrastive analysis patients received radical concurrent chemoradiation therapy, and the 1-, 2-, 3- and 5-year overall survival (OS) rates and median survival time (MST) were 54.3% vs. 37.2%, 27.2% vs. 7.5%, 24.9% vs. 4.8%, 8.3% vs. 0%, and 14 months vs. 10 months ( χ 2 = 13.180, P=0.000). Multivariate analysis showed that PTV ≥63 Gy was an independent favourable factor for survival. Conclusion: Concurrent chemotherapy and three-dimensional radiotherapy to the primary tumour in stage IV squamous NSCLC could prolong survival, and with increasing intensity of comprehensive treatment, OS gradually improved. PTV ≥63 Gy is the independent prognostic factors for OS. [Key Words] Stage IV; Squamous non-small cell lung cancer (NSCLC); Concurrent chemoradiotherapy; Overall survival

Phase III Study of Matrix Metalloproteinase Inhibitor Prinomastat in Non–Small-Cell Lung Cancer

2005 ◽  
Vol 23 (4) ◽  
pp. 842-849 ◽  
Author(s):  
Donald Bissett ◽  
Ken J. O’Byrne ◽  
J. von Pawel ◽  
Ulrich Gatzemeier ◽  
Allan Price ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Extracellular Proteins ◽  
Phase Iii ◽  
Survival Times ◽  
Small Cell Lung ◽  
Study Results

Purpose Matrix metalloproteinases (MMPs) degrade extracellular proteins and facilitate tumor growth, invasion, metastasis, and angiogenesis. This trial was undertaken to determine the effect of prinomastat, an inhibitor of selected MMPs, on the survival of patients with advanced non–small-cell lung cancer (NSCLC), when given in combination with gemcitabine-cisplatin chemotherapy. Patients and Methods Chemotherapy-naive patients were randomly assigned to receive prinomastat 15 mg or placebo twice daily orally continuously, in combination with gemcitabine 1,250 mg/m2 days 1 and 8 plus cisplatin 75 mg/m2 day 1, every 21 days for up to six cycles. The planned sample size was 420 patients. Results Study results at an interim analysis and lack of efficacy in another phase III trial prompted early closure of this study. There were 362 patients randomized (181 on prinomastat and 181 on placebo). One hundred thirty-four patients had stage IIIB disease with T4 primary tumor, 193 had stage IV disease, and 34 had recurrent disease (one enrolled patient was ineligible with stage IIIA disease). Overall response rates for the two treatment arms were similar (27% for prinomastat v 26% for placebo; P = .81). There was no difference in overall survival or time to progression; for prinomastat versus placebo patients, the median overall survival times were 11.5 versus 10.8 months (P = .82), 1-year survival rates were 43% v 38% (P = .45), and progression-free survival times were 6.1 v 5.5 months (P = .11), respectively. The toxicities of prinomastat were arthralgia, stiffness, and joint swelling. Treatment interruption was required in 38% of prinomastat patients and 12% of placebo patients. Conclusion Prinomastat does not improve the outcome of chemotherapy in advanced NSCLC.

Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non–Small-Cell Lung Cancer

2008 ◽  
Vol 26 (21) ◽  
pp. 3543-3551 ◽  
Author(s):  
Giorgio Vittorio Scagliotti ◽  
Purvish Parikh ◽  
Joachim von Pawel ◽  
Bonne Biesma ◽  
Johan Vansteenkiste ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Group Performance ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Phase Iii Study ◽  
Grade 3

PurposeCisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non–small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting.Patients and MethodsThis noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2on day 1 and gemcitabine 1,250 mg/m2on days 1 and 8 (n = 863) or cisplatin 75 mg/m2and pemetrexed 500 mg/m2on day 1 (n = 862) every 3 weeks for up to six cycles.ResultsOverall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P ≤ .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common.ConclusionIn advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer: a phase II toxicity, response, and survival analysis.

1995 ◽  
Vol 13 (8) ◽  
pp. 1860-1870 ◽  
Author(s):  
C J Langer ◽  
J C Leighton ◽  
R L Comis ◽  
P J O'Dwyer ◽  
C A McAleer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Survival Time ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Phase Iii ◽  
Disease Stage ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE To determine the activity and toxicity of combination paclitaxel (24 hours) and carboplatin in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Eligibility required measurable disease (stage IV or stage IIIB with malignant pleural effusion), Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, absolute neutrophil count > or = 2,000/microL, platelet count > or = 100,000/microL serum creatinine concentration < or = 1.5 mg/dL, and bilirubin level < or = 2 mg/dL. Paclitaxel was initially administered at a dose of 135 mg/m2/d, followed by carboplatin on day 2 at a targeted area under the concentration-time curve (AUC) of 7.5 using the Calvert formula. Granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg subcutaneously (SC) on days 3 to 17 was introduced during the second and subsequent cycles. In patients who sustained less than grade 4 myelosuppression, the paclitaxel dose was sequentially escalated 40 mg/m2 per cycle to a maximum of 215 mg/m2. Treatment was repeated at 3-week intervals for six cycles. RESULTS From June 1993 through February 1994, 54 patients were enrolled; 53 are assessable for toxicity and response. The median age was 62 years (range, 34 to 84). Sixty-nine percent were male, 65% had adenocarcinoma, and 93% had stage IV disease. Two hundred sixty-eight cycles were administered; 32 patients (59%) completed all six cycles. Twenty-five unanticipated hospitalizations occurred during treatment (9.3% of cycles) in 20 patients (37%). Myelosuppression was the principal toxicity; grade 3 or 4 granulocytopenia occurred in 57% of patients after the first cycle, but decreased to 35% during the second cycle after introduction of G-CSF and consistently remained < or = 22% during subsequent cycles. Seven episodes of neutropenic fever occurred, all during the first cycle. Grade 3 or 4 thrombocytopenia and anemia occurred in 47% and 33% of patients, respectively. Eight patients (15%) required platelet transfusions and 16 (30%) required packed RBC support. Neuropathy, myalgias/arthralgias, and thrombocytopenia, although generally mild, were cumulative. The paclitaxel dose was boosted to 215 mg/m2 in > or = 70% of patients who received three or more cycles. At an AUC of 7.5, the median first-cycle carboplatin dose was 424 mg/m2 (range, 273 to 709 mg/m2). The objective response rate was 62%, with five (9%) complete responses and 28 (53%) partial responses. The median progression-free survival time was 28 weeks and the median survival time 53 weeks. The 1-year survival rate is 54%. CONCLUSION The paclitaxel-carboplatin combination is active in advanced NSCLC and may enhance survival; it merits further investigation in phase III trials.

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