Immunotherapy plus chemotherapy versus chemotherapy alone in metastatic non–small-cell lung cancer: A systematic review with meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20700-e20700
Author(s):  
Andre Deeke Sasse ◽  
Fernanda Proa Ferreira ◽  
Adolfo Jose de Oliveira Scherr ◽  
David Pinheiro Cunha ◽  
Vivian Castro Antunes Vasconcelos ◽  
...  

e20700 Background: Palliative systemic therapy is the primary approach for stage IV non-small cell lung cancer(NSCLC). For patients with NSCLC that lacks targetable mutations, immunotherapy alone or in combination with chemotherapy has become a promising alternative, focusing survival and quality of life. Our objectives were to review, summarize and compare the evidence of immunotherapy plus chemotherapy in first-line treatment in comparison with chemotherapy alone in patients with metastatic NSCLC in terms of effectiveness. Methods: A systematic review of randomized controlled trials (RCTs) was planned. PubMed, Embase and Lilacs were searched for trials evaluating metastatic NSCLC patients, comparing chemotherapy alone versus chemotherapy plus anti-PD1, anti-PDL1 or anti-CTLA-4 agents. Four investigators independently extracted characteristics and results of identified studies and performed standardized quality ratings. Meta-analyses for overall survival (OS), progression-free-survival (PFS), overall response rates (ORR) and toxicities were performed. Results: Six RCTs met the inclusion criteria. One trial with anti-PD-L1 (Atezolizumab), three trials with anti-PD-1 (Pembrolizumab) and two trials with anti-CTLA-4 (Ipilimumab) were included. Three trials included non-squamous carcinomas, two trials included squamous cell carcinoma and one trial included all NSCLC. The combination of anti-PD-1 or anti-PDL1 to chemotherapy improved OS (Hazard Ratio [HR] for death, 0.62; 95% confidence interval [CI], 0.49 to 0.79; p < 0.0001). This combination also improved PFS (HR for progression or death, 0.57; 95% CI, 0.51 to 0.63; p < 0.00001) and ORR (Odds Ratio [OR], 2.55; 95% CI, 1.80 to 3.61; p < 0.00001). The combination of anti-CTLA-4 to chemotherapy slightly increased the PFS (HR 0.84; 95% CI, 0.73 to 0.96; p = 0.01), but not OS (HR 0.92; 95% CI, 0.80 to 1.05; p = 0.21) or ORR (OR 0.92; 95% CI, 0.71 to 1.19; p = 0.52). General and immune mediated adverse events were higher in all combination groups. Conclusions: In patients with previously untreated metastatic squamous and non-squamous NSCLC without EGFR or ALK mutations, the addition of anti-PD-1 or anti-PD-L1 to standard chemotherapy resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.

2017 ◽  
Vol 35 (24) ◽  
pp. 2790-2797 ◽  
Author(s):  
Rebecca Suk Heist ◽  
Michael J. Guarino ◽  
Gregory Masters ◽  
W. Thomas Purcell ◽  
Alexander N. Starodub ◽  
...  

Purpose Trop-2, expressed in most solid cancers, may be a target for antibody-drug conjugates (ADCs) in non–small-cell lung cancer (NSCLC). We studied sacituzumab govitecan (IMMU-132), a Trop-2 ADC, for the targeting of SN-38. Patients and Methods We evaluated IMMU-132 in a single-arm multicenter trial in patients with pretreated metastatic NSCLC who received either 8 or 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end points were safety and objective response rate (ORR). Progression-free survival and overall survival were secondary end points. Results Fifty-four patients were treated. In the response-assessable study population (n = 47), which had a median of three prior therapies (range, two to seven), the ORR was 19%; median response duration, 6.0 months (95% CI, 4.8 to 8.3 months); and clinical benefit rate (complete response + partial response + stable disease ≥ 4 months), 43%. ORR in the intention-to-treat (ITT) population was 17% (nine of 54). Responses occurred with a median onset of 3.8 months, including patients who had relapsed or progressed after immune checkpoint inhibitor therapy. Median ITT progression-free survival was 5.2 months (95% CI, 3.2 to 7.1 months) and median ITT overall survival, 9.5 months (95% CI, 5.9 to 16.7 months). Grade 3 or higher adverse events included neutropenia (28%), diarrhea (7%), nausea (7%), fatigue (6%), and febrile neutropenia (4%). One patient developed a transient immune response, despite patients receiving a median of 10 doses. More than 90% of 26 assessable archival tumor specimens were highly positive (2+, 3+) for Trop-2 by immunohistochemistry, which suggests that Trop-2 is not a predictive biomarker for response. Conclusion IMMU-132 was well-tolerated and induced durable responses in heavily pretreated patients with metastatic NSCLC. This ADC should be studied further in this disease and in other patients with Trop-2–expressing tumors.


2021 ◽  
pp. 38-38
Author(s):  
Bojan Radojicic ◽  
Marija Radojicic ◽  
Miroslav Misovic ◽  
Dejan Kostic

Background/Aim. About 1.8 million new lung cancer cases are diagnosed in the world every year, and about 1.6 million cases are with fatal outcome. Despite improvements in treatment in previous decades, the survival of patients with lung cancer is still poor. The five-year survival rate is about 50% for patients with localized disease, 20% for patients with regionally advanced disease, 2% for patients with metastatic disease, and about 14% for all stages. The median survival of patients with untreated NSCLC in the advanced stage is four to five months and the annual survival rate is only 10%. The main goal of the research is to obtain and analyze the results of treatment with concomitant chemotherapy in terms of its efficacy and toxicity in selected patients with locally advanced inoperable non-small cell lung cancer. Methods. The study included data analysis of 31 patients of both sexes who were diagnosed and pathohistologically verified with NSCLC in inoperable stage III and were referred by the Council for Malignant Lung Diseases to the Radiotherapy Department of the Military Medical Academy for concomitant chemoradiotherapy treatment. Upon expiry of the three-month period from the performed radiation treatment, the tumor resonance was assessed on the basis of MSCT examination of the chest and upper abdomen according to RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors). According to the same criteria, progression-free survival (PFS) was also assessed every three months during the first two years, then every 6 months or until the onset of disease symptoms, as well as overall survival (OS). Result. The median progression-free survival is 13 months, and the median overall survival is 20 months. During and immediately after RT, 9 (29%) patients had a grade 2 or higher adverse event. Conclusion. The use of concomitant chemoradiotherapy in patients in the third stage of locally advanced inoperable non-small cell lung cancer provides a good opportunity for a favorable therapeutic outcome, with an acceptable degree of acute and late toxicity, and represents the standard therapeutic approach for selected patients in this stage of the disease.


2020 ◽  
Vol 16 (27) ◽  
pp. 2045-2058 ◽  
Author(s):  
Yong-Jin Kim ◽  
Mark Oremus ◽  
Helen H Chen ◽  
Thomas McFarlane ◽  
Devanshi Shah ◽  
...  

Background: The effectiveness of immunotherapies for non-small-cell lung cancer under real-world clinical settings remains uncertain. Materials & methods: Systematic searches of PubMed, EMBASE and Web of Science were conducted. Random-effects models were used to estimate pooled median overall survival and progression-free survival estimates. Results: 36 studies of nivolumab were included for narrative synthesis and 11 of these studies were included for meta-analysis. Age, sex, histology and prior lines of treatment did not affect survival outcomes, while Eastern Cooperative Oncology Group Performance Status and brain metastasis were inversely associated with survival. In the meta-analysis, nivolumab was associated with 9.6 months (95% CI: 8.4–10.9) of overall survival and 2.6 months (95% CI: 1.6–3.6) of progression-free survival. Conclusion: Very-low-certainty evidence suggested the real-world effectiveness of nivolumab was consistent with those observed in the clinical trials.


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