Comparison of the outcome between immunotherapy alone or in combination with chemotherapy in EGFR-mutant non-small cell lung cancer.
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ABSTRACT:
SUBMITTER: Shen CI
PROVIDER: S-EPMC8352947 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There is a lack of direct cross-comparison studies in clinical trials between immunotherapy alone and combination treatment, especially in Non-Small Cell Lung Cancer (NSCLC) patients with high PD-L1 expression. To determine if anti-PD-(L)1 antibody combined with chemotherapy is more efficient than immune checkpoint inhibitor (ICI) monotherapy for advanced NSCLC patients in the real-world data. We retrospectively collected 325 patients with advanced NSCLC treated with ICI alone with or without chemotherapy from 11th July 2016 to 26th May 2020 to investigate which treatment scenario is the most efficient, and how clinical factors impact response. Patients with advanced NSCLC were treated with ICI monotherapy (178/325, 54.8%) or in combination with chemotherapy (147/325, 45.2%). The objective response rate and disease control rate were higher in the combination group than the monotherapy group. Patients (including those with distant metastasis) treated with chemo-immunotherapy were associated with a significantly longer median PFS and OS compared with the monotherapy group, irrespective of the PD-L1 expression level and previous treatment lines. No significant increase in the risk of immune-related adverse events (irAEs) was found after combination with chemotherapy (50.6 vs. 57.8%). IrAEs predicted better PFS of immunotherapy in the monotherapy group, especially for patients with late irAEs (after ≥4 cycles). Collectively, we demonstrated that ICI monotherapy plus chemotherapy might have better anti-tumor activity and an acceptable side-effect profile regardless of PD-L1 level or previous treatment lines. Both regimens were well-tolerated and cost-effective, the more efficient is usually recommended.
| S-EPMC8013714 | biostudies-literature
Project description:Immune checkpoint inhibitors enhance the activation and antitumor activity of the immune system, resulting in durable response rates in a select group of patients. Cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors target the inhibitory interaction between CTLA4 and CD80 or CD86. Programmed death 1 (PD1) inhibitors target the interaction between PD1 receptors on T-cells and PD-ligand 1 (PD-L1) and PD-ligand 2, blocking the inhibitory signaling and resulting in activation of T-cell effector function. These therapeutic drugs were originally evaluated in patients with metastatic melanoma before expansion to all tumor types, including non-small cell lung cancer (NSCLC) with promising results. The PD1 inhibitors such as pembrolizumab have now received FDA approval in the first-line setting for patients with positive PD-L1 expression tumor types; however, only a portion of patients have shown objective and sustainable responses. To expand the number of patients with observed response to immunotherapeutic agents including patients with negative PD-L1 expression tumors, clinical trials are ongoing to assess the safety and efficacy of combination immune checkpoint inhibitors and combination immune checkpoint inhibitors with targeted therapy. Immune checkpoint inhibitors have been found to be a promising therapeutic drug class with sustainable response rates and a tolerable safety profile, and efforts continue to improve these drugs in patients with NSCLC.
| S-EPMC5861267 | biostudies-literature
Project description:ObjectivesUse of immune checkpoint inhibitors as first-line treatment for advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC) remains controversial. Clinical trials comparing single-drug immunotherapy (IO) with immunotherapy plus chemotherapy (IC) are lacking. We aimed to compare the efficacy of IO alone with that of IC as first-line treatment for advanced NSCLC.DesignSystematic review.Data sourcesPubMed, the Cochrane Library and Embase for related studies on NSCLC; ClinicalTrials.gov, American Society of Clinical Oncology Meeting Library and World Conference on Lung Cancer for relevant conference abstracts (to July 2019).Eligibility criteriaArticles meeting the following criteria were selected: (1) randomised controlled trials on NSCLC treatment, (2) all individuals in the studies had not received treatment previously and (3) research on IO monotherapy using programmed death-1/programmed death ligand-1 (PD-L1) inhibitors or IC.Data extraction and synthesisAfter reading the original literature, two reviewers independently extracted the relevant information. The primary outcomes were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). We also extracted data on treatment-related adverse events and immune-related adverse events (irAEs).ResultsOverall, 10 randomised controlled clinical trials (n=5765) were included. As first-line treatment for advanced NSCLC, IC tended to yield better PFS, OS and ORR than did IO. Furthermore, IC yielded significantly better PFS than IO when tumour PD-L1 expression was at least 50% (HR: 1.81, 95% CI: 1.18 to 2.78) and yielded a better OS and PFS when tumour PD-L1 expression was at least 1%; IO resulted in fewer adverse events than did IC. However, the incidence of irAEs was higher for IO than for IC.ConclusionsThe findings of the indirect comparison indicate that IC as first-line treatment for advanced NSCLC is significantly more effective than IO in patients with PD-L1 expression in at least 50% of tumour cells.Trial registration numberCRD 42018116589.
| S-EPMC7682470 | biostudies-literature
Project description: Not available
| S-EPMC6835106 | biostudies-literature
Project description:Importance: Checkpoint inhibitor pneumonitis (CIP) is a rare but serious adverse event that may impact treatment decisions. However, there is limited information comparing CIP risks between immune checkpoint inhibitor (ICI) monotherapy and combination with chemotherapy due to a lack of direct cross-comparison in clinical trials. Objective: To determine whether ICI combination with chemotherapy is superior to ICI in other drug regimens (including monotherapy) in terms of CIP risk. Study Design and Methods: This observational, cross-sectional and worldwide pharmacovigilance cohort study included patients who developed CIP from the World Health Organization database (WHO) VigiBase and the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Individual case safety reports (ICSR) were extracted from 2015 to 2020 in FAERS and from 1967 to 2020 in VigiBase. Timing and reporting odds ratio (ROR) of CIP in different treatment strategies were used to detect time-to-onset and the risk of pneumonitis after different immunotherapy regimens. Results: A total of 93,623 and 114,704 ICI-associated ICSRs were included in this study from VigiBase and FAERS databases respectively. 3450 (3.69%) and 3278 (2.86%) CIPs occurred after therapy initiation with a median of 62 days (VigiBase) and 40 days (FAERS). Among all the CIPs, 274 (7.9%) and 537 (16.4%) CIPs were associated with combination therapies. ICIs plus chemotherapy combination was associated with pneumonitis in both VigiBase [ROR 1.35, 95% CI 1.18-1.52] and FAERS [ROR 1.39, 95% CI 1.27-1.53]. The combination of anti-PD-1 antibodies and anti-CTLA-4 antibodies with chemotherapy demonstrated an association with pneumonitis in both VigiBase [PD-1+chemotherapy: 1.76, 95% CI 1.52-2.05; CTLA-4+chemotherapy: 2.36, 95% CI 1.67-3.35] and FAERS [PD-1+chemotherapy: 1.70, 95% CI 1.52-1.91; CTLA-4+chemotherapy: 1.70, 95% CI 1.31-2.20]. Anti-PD-L1 antibodies plus chemotherapy combinations did not show the association. Conclusion: Compared to ICI in other drug regimens (including monotherapy), the combination of ICI plus chemotherapy is significantly associated with higher pneumonitis toxicity. Anti-PD-1/CTLA4 medications in combination with chemotherapy should be obviated in patients with potential risk factors for CIP. Trial Registration: clinicaltrials.gov, ChiCTR2200059067.
| S-EPMC10133569 | biostudies-literature
Project description:Simple Summary Although it is known that anti-PD1/L1 monotherapy does not render significant benefit in patients with EGFR-mutant lung adenocarcinoma, whether the addition of anti-PD1/L1 therapy to chemotherapy can enhance chemotherapy efficacy for TKI-refractory EGFR-mutant lung adenocarcinoma patients is not clear. To address this question, we retrospectively analyzed a cohort of 178 EGFR-mutant lung adenocarcinoma patients who had progressed on EGFR TKIs and received subsequent non-TKI systemic therapy to determine whether the addition of immunotherapy to chemotherapy truly improves clinical outcomes. We found that the addition of anti-PD1 immunotherapy did not add benefit to the platinum-based chemotherapy at the time of TKI progression for EGFR-mutant LUAD. Although underpowered, the anti-VEGF therapy demonstrated a trend towards adding benefit. As ongoing clinical trials with newer agents or combinations demonstrate preliminary efficacy in TKI-resistant EGFR-mutant LUAD patients, the ideal choice for post-TKI treatment is still being evaluated. Abstract Background: The benefit of chemotherapy combined with immunotherapy in EGFR-mutant lung adenocarcinoma (LUAD) patients whose tumor developed resistance to EGFR tyrosine kinase inhibitors (TKIs) is not thoroughly investigated. The goal of this retrospective cohort study is to assess the clinical efficiency of immunotherapy alone or in combination with chemotherapy in a real-world setting. Methods: This retrospective cohort study enrolled LUAD patients with EGFR sensitive mutations whose tumor had acquired resistance to EGFR TKIs and received systemic treatment with chemotherapy (chemo; n = 84), chemotherapy combined with immunotherapy (chemoIO; n = 30), chemotherapy plus bevacizumab with or without IO (withBev; n = 42), and IO monotherapy (IO-mono; n = 22). Clinical progression-free survival (PFS) and overall survival (OS) were evaluated. Associations of clinical characteristics with outcomes were assessed using univariable and multi-covariate Cox Proportional Hazards regression models. Results: A total of 178 patients (median age = 63.3; 57.9% females) with a median follow-up time of 42.0 (Interquartile range: 22.9–67.8) months were enrolled. There was no significant difference in PFS between chemoIO vs. chemo groups (5.3 vs. 4.8 months, p = 0.8). Compared to the chemo group, patients who received withBev therapy trended towards better PFS (6.1 months vs. 4.8; p = 0.3; HR 0.79; 95% CI: 0.52–1.20), while patients treated with IO-mono had inferior PFS (2.2 months; p = 0.001; HR 2.22; 95% CI: 1.37–3.59). Furthermore, PD-L1 level was not associated with PFS benefit in the chemoIO group. Patients with EGFR-mutant LUAD with high PD-L1 (≥50%) had shorter PFS (5.8 months) than non-EGFR/ALK LUAD patients who received chemoIO (12.8 months, p = 0.002; HR 0.22; 95% CI: 0.08–0.56) as first-line treatment. Chemotherapy-based therapy rendered similar benefit to patients with either EGFR exon19 deletion vs. L858R in the LUAD. Conclusions: This retrospective analysis revealed that immunotherapy provided limited additional benefit to chemotherapy in TKI-refractory EGFR-mutant LUAD. Chemotherapy alone or combined with bevacizumab remain good choices for patients with actionable EGFR mutations.
| S-EPMC9323840 | biostudies-literature
Project description:Osimertinib is a third-generation, irreversible oral EGFR-tyrosine kinase inhibitor), that potently inhibits EGFR-tyrosine kinase inhibitor-sensitizing mutations and T790M resistance mutations together with efficacy in CNS metastases in patients with non-small-cell lung cancer (NSCLC). Here we describe the rationale and design for the Phase III NeoADAURA study (NCT04351555), which will evaluate neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone prior to surgery, in patients with resectable stage II-IIIB N2 EGFR mutation-positive NSCLC. The primary end point is centrally assessed major pathological response at the time of resection. Secondary end points include event-free survival, pathological complete response, nodal downstaging at the time of surgery, disease-free survival, overall survival and health-related quality of life. Safety and tolerability will also be assessed. Trial Registration number: NCT04351555 (ClinicalTrials.gov).
| S-EPMC8530153 | biostudies-literature
Project description:Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) are standard treatment for advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. However, EGFR mutation testing is not attainable in approximately 20% of patients. The current study examined intercalating and maintaining gefitinib treatment in stage IIIB/IV non-squamous NSCLC, never or former light smoking patients with unknown EGFR mutation status. Briefly, 219 patients who achieved stable disease (SD) with gemcitabine (1250 mg/m2) plus carboplatin (5 AUC) were randomized at 1:1 ratio to continue chemotherapy (n = 110) or intercalating gefitinib (250 mg/day on days 15-25 of each cycle until disease progress (n = 109). Progression-free survival (PFS) was 9.7 vs. 4.2 month in the gefitinib vs. control arm (HR: 0.41, 95% CI: 0.31-0.56; P < 0.001). Overall survival (OS) was also longer in the gefitinib arm (20.1 vs. 15.4 months; HR: 0.68; 95% CI 0.48-0.97; P = 0.0323). Adverse events, including diarrhea, dermal reaction and thrombocytopenia, were more common in the gefitinib arm. In conclusion, intercalating and maintenance gefitinib treatment is a viable option for advanced NSCLC patients with unknown EGFR mutation status in subpopulations with high EFGR mutation rate.
| S-EPMC5559626 | biostudies-other
Project description:Both chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are widely applied for the treatment of non-small cell lung cancer (NSCLC), but the efficacy of these two treatments in combination is not yet clear. Thus, we sought to evaluate the efficacy of the intercalated combination of these two treatments in NSCLC. The PubMed database, EMBASE, Cochrane Controlled Trials Register, and Chinese Biomedical Database were systematically searched by two researchers for randomized clinical trials (RCTs) that examined the intercalated combination of chemotherapy and EGFR TKIs in NSCLC. Ten studies involving 1,660 patients were included in this systematic review. The statistical results showed that the intercalated combination of chemotherapy and EGFR TKIs significantly improved overall survival (OS) (hazard ratio (HR)?=?0.83, 95% confidence interval (CI): 0.70-0.98), progression-free survival (PFS) (HR?=?0.65, 95% CI: 0.51-0.84), and the objective response rate (ORR) (risk ratio (RR)?=?1.90, 95% CI: 1.22-2.98) compared to chemotherapy alone. Similarly, compared to EGFR TKIs monotherapy, the intercalated combination of chemotherapy and EGFR TKIs seemed superior to EGFR TKIs alone in terms of PFS, ORR and DCR (PFS: HR?=?0.75, 95% CI: 0.62-0.91, ORR: RR?=?1.49, 95% CI: 1.12-2.00 and DCR: RR?=?1.33, 95% CI: 1.15-1.54) in advanced NSCLC therapy.
| S-EPMC4611484 | biostudies-literature
Project description:Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer has an oncogene-addicted biology that confers sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Published data suggest that EGFR addiction persists after development of TKI acquired resistance, leading many clinicians to continue TKI with subsequent chemotherapy; however, this strategy has not been formally evaluated. Methods. We retrospectively reviewed an institutional database to identify patients with advanced EGFR mutation with acquired resistance who subsequently received chemotherapy. Patients were classified as receiving chemotherapy with continued erlotinib or chemotherapy alone. We assessed differences in outcomes between the two strategies. Results. Seventy-eight patients were included, 34 treated with chemotherapy and erlotinib and 44 treated with chemotherapy alone. Objective response rate was evaluable in 57 patients and was 41% for those treated with chemotherapy and erlotinib and 18% for those treated with chemotherapy alone. After adjusting for chemotherapy regimen and length of initial TKI course, the odds ratio for the response rate was 0.20 (95% confidence interval: 0.05-0.78; p = .02) favoring treatment with chemotherapy and erlotinib. The median progression-free survival was 4.4 months on chemotherapy and erlotinib and 4.2 months on chemotherapy alone (adjusted hazard ratio = 0.79; 95% confidence interval: 0.48-1.29; p = .34). There was no difference in overall survival. Conclusion. This is the first study, to our knowledge, to demonstrate that continuation of EGFR TKI with chemotherapy in patients with acquired resistance improves outcomes compared with chemotherapy alone. We observed an improved response rate but no difference in progression-free survival or overall survival. A larger prospective clinical trial is needed to evaluate this promising strategy further.
| S-EPMC3825307 | biostudies-literature