Efficacy and safety of PD-1/PD-L1 antibody combined with chemotherapy as second-line or third-line treatment for metastatic small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20574-e20574
Author(s):  
Jun Wang ◽  
Beibei Yin ◽  
Yaping Guan ◽  
Dongfeng Feng
Keyword(s):  
Lung Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
Extensive Stage ◽  
Grade 3

e20574 Background: For a small subset of patients, immune checkpoint blockade heralds a promising strategy for achieving disease control in small cell lung cancer (SCLC). Nivolumab or pembrolizumab monotherapy has been granted accelerated approval for treatment of patients with extensive-stage SCLC with disease progression after platinum-based chemotherapy and at least one other line of therapy. Moreover, Based on IMpower133 and CASPIAN data, addition of PD-L1 antibody such as atezolizumab or durvalumab to first-line platinum-based chemotherapy prolongs overall survival over chemotherapy alone. However, it remains exclusive that whether PD-1/PD-L1 antibody combined with chemotherapy is effective against extensive-stage SCLC when progressed on previous chemotherapy. Methods: We reviewed patients with extensive-stage SCLC who have failed in first-line or beyond chemotherapy and received PD-1/PD-L1 antibodies with chemotherapy in a single institute. The efficacy and safety were evaluated. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Results: A total of 11 patients were included in this retrospective cohort study. The median age was 46 years (range from 29 to 62). Seven patients were male. Four were current or former smokers. Six received two prior therapies. Nine had previously received radiation therapy. PD-1 and PD-L1 inhibitors were administrated in 5 and 6 patients, respectively. No patient had a complete response. 2 patients had a partial response, and the objective response rate was 18.2%. 5 patients were evaluated as stable disease with a disease control rate of 63.6%. The median overall survival and progression-free survival was 3.0 months and 2.3 months, respectively. A patient with partial response had a long duration of response of 5.2 months. The most common grade 3 or 4 treatment-related were neutropenia, anemia, and decreased neutrophil count. Most immune-related adverse events were grade 1 or 2, with rash, pruritus and hypothyroidism being the most common, and 1 patient had grade 3 pneumonia. Conclusions: Immunotherapy plus chemotherapy could be beneficial for a subgroup of extensive-stage SCLC patients who have progressed after previous chemotherapy. Further prospective, randomized studies are warranted.

Efficacy and safety of toripalimab with anlotinib and chemotherapy as first-line therapy in patients with extensive-stage small-cell lung cancer: Preliminary results of an open-label, single-arm, phase II study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20570-e20570
Author(s):  
Hao Luo ◽  
Dan Jian ◽  
Yan Feng ◽  
Li Zhong ◽  
Qian Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Objective Response ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
First Line ◽  
Treatment Naïve ◽  
Extensive Stage

e20570 Background: Although the combination of PD-1/PD-L1 immune checkpoint inhibitors (ICIs) with platinum-etoposide chemotherapy (EP) is the preferred first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC), the survival benefit of the addition of ICIs was still modest. Recent studies supported that combination of ICIs and anti-angiogenic agents could be a promising therapeutic strategy for normalization the immunosuppressive microenvironment and overcoming the low efficacy of ICIs. We reported the efficacy and safety of toripalimab combined with anlotinib and EP in treatment-naïve ES-SCLC. Methods: The eligible ES-SCLC patients (18-75 years, ECOG PS ≤2), with measurable target lesion (RECIST v1.1) received toripalimab (240 mg, d1) combined with etoposide (100 mg/m2, d1-3) plus carboplatin (AUC = 5, d1)/cisplatin (75 mg/m2, d1) and anlotinib (12 mg QD, d1-14) of a 21-day cycle for 4-6 cycles, then patients with CR、PR or SD could continue to receive maintenance therapy with toripalimab and anlotinib until disease progression. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Results: Between 2018 October and 2020 November, 16 treatment-naïve ES-SCLC patients (14 males, 2 females) were enrolled. The median age is 63 (range, 42-74) years. The median follow-up was 7.6 months. 100% (16/16) patients achieved an objective response (1 CR and 15 PR). The DCR was also 100% (16/16). The median DOR had not been reached (range, 4.8+ to 21.9+ month). 37.5% (6/16) patients had disease progression after six months of treatment, while median PFS was not reached. As of Jan 31, 2021, all patients were still alive. The median OS had not been reached. 62.5% (10/16) patients remained on-treatment. The most common adverse events (AEs) were grade 1-2 anemia (75%), decreased appetite (50%) and neutropenia (43.8%). Seven patients had Grade 3 AEs (5 neutropenia; 1 leukopenia, 1 emesis, and 1 ketoacidosis). No Grade 4/5 AEs occurred. Conclusions: Toripalimab combined with anlotinib and etoposide plus carboplatin/cisplatin showed promising anti-tumor activity and tolerable toxicities in treatment-naïve ES-SCLC. Clinical trial information: NCT04731909.

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

scholarly journals Comparative efficacy and safety of first-line treatments for advanced non-small cell lung cancer with ALK-rearranged: a meta-analysis of clinical trials

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hao-chuan Ma ◽  
Yi-hong Liu ◽  
Kai-lin Ding ◽  
Yu-feng Liu ◽  
Wen-jie Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Options ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
First Line ◽  
Grade 3

Abstract Background Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC. Methods We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases. Results A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%). Conclusion Our analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape.

Clinical significance of ERCC2 haplotype-tagging single nucleotide polymorphisms in patients with unresectable non-small cell lung cancer treated with first-line platinum-based chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19156-e19156
Author(s):  
Seok-Hyun Kim ◽  
Gyeong-won Lee ◽  
Yi Yeong Jeong ◽  
Ho-Cheol Kim ◽  
Jong Deog Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell ◽  
Rank Test ◽  
Nucleotide Polymorphisms ◽  
Small Cell Lung ◽  
First Line ◽  
Single Nucleotide ◽  
Log Rank Test ◽  
Platinum Based Chemotherapy ◽  
Grade 3

e19156 Background: DNA repair pathway is a crucial molecular mechanism potentially involved in resistance to platinum-based chemotherapy in the unresectable non-small cell lung cancer. Furthermore, single nucleotide polymorphisms (SNPs) and haplotypes in the ERCC2 gene are thought to be associated with the risk of developing lung cancer and clinical outcomes. Methods: We genotyped 8 ERCC2 htSNPs for 129 unresectable NSCLC (stage IIIA, 12; stage III, 36; stage IV, 82) cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, and predictive value of htSNPs in patient response, survival, and chemotherapy-related adverse events were analyzed according to each ERCC2 htSNP using chi-square test, Kaplan-Meier method, and Cox proportional hazard model. Results: No differences were observed in patient or disease characteristics and response according to ERCC2 htSNPs. In a survival analysis, rs50872 was significantly related to overall survival (OS) (log-rank test, p=0.014). The median survival duration of rs50872 G/G, A/G, and A/A genotypes was 35.75 (95% confidence interval [CI] 21.05-50.45), 36.07 (hazard ratio[HR] 1.02, 95% CI 25.20-46.94), and 16.75 (HR 3.49, 95% CI 5.73-27.77) months, respectively. A significant association was observed between grade 3-4 infections and poor survival: OS in patients with a grade 0-2 infection: 35.75 months (95% CI 28.15-43.35); OS in patients with a grade 3-4 infection: 12.86 months (95% CI 8.99-16.72, HR 3.57) (log-rank test, p<0.001). In a subgroup analysis, rs238405 genotype was significantly related to OS in the taxane-based group. However, rs238416 genotype was significantly associated with OS in the gemcitabine-based group. Conclusions: ERCC2 htSNPs rs50872 (overall), rs238405 (taxane-based group), and rs238416 (gemcitabine-based group) and infection related to first-line chemotherapy were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. However, additional large prospective studies focusing on the role of ERCC2 htSNPs in unresectable NSCLC are needed.

scholarly journals Carboplatin versus cisplatin in combination with etoposide in the first-line treatment of small cell lung cancer: a pooled analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shiyu Jiang ◽  
Liling Huang ◽  
Hongnan Zhen ◽  
Peijie Jin ◽  
Jing Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Eastern Cooperative Oncology Group ◽  
Small Cell ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
First Line ◽  
Grade 3

Abstract Background Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive disease with poor survival, and platinum-etoposide chemotherapy is indicated as the mainstay of treatment. In this study, we compared the efficacy and safety between the cisplatin plus etoposide (EP) and carboplatin plus etoposide (EC) regimens. Methods A total of 1305 patients with previously untreated ES-SCLC were included in this study. Data from five trials were collected from the public database Project Data Sphere. Survival analysis and adverse events (AEs) analysis were conducted. Results Of the 1305 patients, 800 received the EC regimen whereas 505 received the EP regimen as their front-line treatment. Overall, the median progression-free survival (PFS) and the median overall survival (OS) were 172 and 289 days, respectively. The EP and EC treatment groups did not have significantly different PFS or OS. After adjusting for age, sex, body mass index (BMI) and Eastern Cooperative Oncology Group (ECOG) performance status (PS), the EP regimen was independently associated with better PFS (hazard ratio [HR] = 0.76, 95% CI = 0.63–0.92, p = 0.0041) and OS (HR = 0.79, 95% CI = 0.64–0.97, p = 0.0220) among patients who were overweight and obese (BMI ≥ 25 kg/m2). In the safety analysis, patients who received the EC treatment experienced significantly more grade ≥ 3 AEs (n = 599, 74.9%) than those who received the EP treatment (n = 337, 66.7%; p = 0.002). Furthermore, the EC regimen was associated with a higher risk of grade 3–4 neutropaenia (p = 0.001), thrombocytopaenia (p < 0.001) and hyponatraemia (p = 0.036), whereas the EP regimen was associated with a higher risk of grade 3–4 vomiting (p = 0.021). Conclusions In summary, this study presented the efficacy and safety of the EC and EP regimens in patients with ES-SCLC in the first-line setting. Patients who are overweight and obese benefit more from the EP regimen than EC regimen. Approaches to define the optimal chemotherapy regimen in different BMI subgroups are needed.

DDRE-04. EFFECTIVENESS AND SAFETY OF OSIMERTINIB FOR PATIENTS WITH LEPTOMENINGEAL METASTASES FORM NON-SMALL CELL LUNG CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi75-vi75
Author(s):  
Lei Wen ◽  
Changguo Shan ◽  
hui Wang ◽  
yanying Yang ◽  
Minting Ye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Adverse Events ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Small Cell ◽  
Leptomeningeal Metastases ◽  
Small Cell Lung ◽  
Grade 3

Abstract BACKGROUND the FLAURA study established Osimertinib to be the priority choice for the treatment of metastatic non-small cell lung cancer (NSCLC) harboring mutated epidermal growth factor receptor (EGFR). However, like many previous studies, the FLAURA study excluded patients with symptomatic CNS metastases. Hence, we performed a systematic review and meta-analyses of studies to assess the efficiency and safety of Osimertinib for the treatment of NSCLC with leptomeningeal metastases (LM). METHODS We included studies published between 2010 and 2021 that evaluated the efficacy and toxicity of Osimertinib in NSCLC patients with LM. We searched PubMed, Embase, and oncology meeting abstracts (ASCO, ESMO and WCLC). Primary outcomes were objective response rate (ORR), disease control rate (DCR), any grade 3/4 toxicity rate. We used the random-effects model to generate pooled estimates for proportions. Newcastle-Ottawa Scale (NOS) was used to assess the certainty in the evidence. RESULTS Twelve studies reporting on 367 patients were included in the meta-analysis. Most patients (≥90%) received Osimertinib as at least second line of treatment. The objective response rate was 42% (95% CI, 24%-59%; n = 184), and CNS disease control rate was 90% (95% CI, 85%-94%; n = 154). Intracranial progression free survival and overall survival ranged from 3.7 to 15.6 months, and 11.0 to 18.8 months, respectively. Adverse events were similar with previous studies and Common Terminology Criteria for Adverse Events (version 3.0) grade 3 or higher adverse event rates was acceptable. CONCLUSION This meta-analysis confirmed that for advanced NSCLC with LM harboring EGFR-TKI-sensitizing mutations, Osimertinib showed impressive antitumor activity and acceptable toxicity.

scholarly journals Real-world outcomes in patients with ALK-positive non-small cell lung cancer treated with crizotinib

2018 ◽  
Vol 25 (1) ◽  
pp. 40 ◽  
Author(s):  
K.L. Davis ◽  
J.A. Kaye ◽  
E.T. Masters ◽  
S. Iyer
Keyword(s):  
United States ◽  
Lung Cancer ◽  
Response Rate ◽  
Objective Response ◽  
The United States ◽  
Treatment Patterns ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Line Therapy

Background Crizotinib has shown greater efficacy in clinical trials than chemotherapy in patients with anaplastic lymphoma kinase-positive (alk+) non-small cell lung cancer (nsclc), but little information is available on its use and outcomes in real-world settings. We therefore assessed treatment patterns and outcomes in alk+ nsclc patients treated with crizotinib in regular clinical practice.Methods A retrospective medical record review was conducted in North America for adults with alk+ nsclc treated with crizotinib as first- or later-line therapy for metastatic disease between 1 August 2011 and 31 March 2013 (for the United States) or 1 May 2012 and 31 March 2013 (for Canada). Crizotinib-related trial enrollees were excluded. Descriptive analyses were conducted to assess treatment patterns and objective response rate (orr). Progression-free survival (pfs) and overall survival (os) were descriptively analyzed using Kaplan-Meier methods.Results Data were extracted for 212 patients in the United States (n = 147) and Canada (n = 65). Mean (standard deviation [sd]) age was 58.9 (9.5) years, and 69% were male. Seventy-nine patients (37%) were deceased at record abstraction. Sixty-five percent (n = 137) initiated crizotinib as first-line therapy. Mean (sd) duration of crizotinib treatment was 8.7 (4.9) months. Objective response rate was 66% (69% for first-line recipients, 60% for second-/laterline). Median (95% ci) pfs and os from crizotinib initiation were 9.5 (8.7, 10.1) and 23.4 (19.5, ‒) months, respectively. One- and two-year survival probabilities were 82% and 49%, respectively.Conclusions Outcomes for crizotinib recipients in this study align with previous trials, with orr appearing more favourable in first-line recipients. Our findings indicate that crizotinib outcomes in clinical studies may translate to regular clinical practice.

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