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ESMO Open Oct 2021The phase III FLAURA2 (NCT04035486) study will evaluate efficacy and safety of first-line osimertinib with platinum-pemetrexed chemotherapy versus osimertinib...
Osimertinib plus platinum-pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study.
BACKGROUND
The phase III FLAURA2 (NCT04035486) study will evaluate efficacy and safety of first-line osimertinib with platinum-pemetrexed chemotherapy versus osimertinib monotherapy in epidermal growth factor receptor mutation-positive (EGFRm) advanced/metastatic non-small-cell lung cancer (NSCLC). The safety run-in, reported here, assessed the safety and tolerability of osimertinib with chemotherapy prior to the randomized phase III evaluation.
PATIENTS AND METHODS
Patients (≥18 years; Japan: ≥20 years) with EGFRm locally advanced/metastatic NSCLC received oral osimertinib 80 mg once daily (QD), with either intravenous (IV) cisplatin 75 mg/m or IV carboplatin target area under the curve 5, plus pemetrexed 500 mg/m every 3 weeks (Q3W) for four cycles. Maintenance was osimertinib 80 mg QD with pemetrexed 500 mg/m Q3W until progression/discontinuation. The primary objective was to evaluate safety and tolerability of the osimertinib-chemotherapy combination.
RESULTS
Thirty patients (15 per group) received treatment [Asian, 73%; female, 63%; median age (range) 61 (45-84) years]. Adverse events (AEs) were reported by 27 patients (90%): osimertinib-carboplatin-pemetrexed, 100%; osimertinib-cisplatin-pemetrexed, 80%. Most common AEs were constipation (60%) with osimertinib-carboplatin-pemetrexed and nausea (60%) with osimertinib-cisplatin-pemetrexed. In both groups, 20% of patients reported serious AEs. No specific pattern of AEs leading to dose modifications/discontinuations was observed; one patient discontinued all study treatments including osimertinib due to pneumonitis (study-specific discontinuation criterion). Hematologic toxicities were as expected and manageable.
CONCLUSIONS
Osimertinib-chemotherapy combination had a manageable safety and tolerability profile in EGFRm advanced/metastatic NSCLC, supporting further assessment in the FLAURA2 randomized phase.
Topics: Acrylamides; Aniline Compounds; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Lung Neoplasms; Middle Aged; Mutation; Pemetrexed; Platinum
PubMed: 34543864
DOI: 10.1016/j.esmoop.2021.100271 -
Journal of Thoracic Oncology : Official... Apr 2021We report the final results of the phase 3 IMpower132 study evaluating atezolizumab plus carboplatin or cisplatin plus pemetrexed (APP) in patients with nonsquamous... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
We report the final results of the phase 3 IMpower132 study evaluating atezolizumab plus carboplatin or cisplatin plus pemetrexed (APP) in patients with nonsquamous NSCLC.
METHODS
Chemotherapy-naive patients with stage IV nonsquamous NSCLC without sensitizing EGFR or ALK genetic alterations were randomized in a one-to-one ratio to receive four or six cycles of carboplatin or cisplatin plus pemetrexed (PP) or APP every 3 weeks, followed by maintenance therapy with atezolizumab plus pemetrexed or pemetrexed alone. Co-primary end points were overall survival (OS) and investigator-assessed progression-free survival (PFS).
RESULTS
The intention-to-treat population included 578 patients (APP, n = 292; PP, n = 286). At the primary PFS analysis (May 22, 2018; median follow-up, 14.8 mo), APP exhibited significant PFS improvement versus PP (median = 7.6 versus 5.2 mo, stratified hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.49-0.72, p < 0.0001). OS for the APP group was numerically better but not statistically significant at the interim (May 22, 2018; median = 18.1 versus 13.6 mo, stratified HR = 0.81, 95% CI: 0.64-1.03, p = 0.0797) and final analyses (July 18, 2019; median = 17.5 versus 13.6 mo; stratified HR = 0.86, 95% CI: 0.71-1.06, p = 0.1546). The OS and PFS results favored APP versus PP across subgroups. Grade 3 or 4 treatment-related adverse events occurred in 54.6% (APP) and 40.1% (PP) of patients; grade 5 treatment-related events occurred in 3.8% and 2.9%, respectively.
CONCLUSIONS
IMpower132 met its co-primary PFS end point but not its co-primary OS end point, with numerical improvement for OS in the APP arm. APP had a manageable safety profile, with no new or unexpected safety signals identified.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cisplatin; Humans; Lung Neoplasms; Pemetrexed
PubMed: 33333328
DOI: 10.1016/j.jtho.2020.11.025 -
Journal of Thoracic Oncology : Official... Oct 2020Sintilimab, an anti-programmed death 1 antibody, plus pemetrexed and platinum had revealed promising efficacy for nonsquamous NSCLC in a phase 1b study. We conducted a... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11).
INTRODUCTION
Sintilimab, an anti-programmed death 1 antibody, plus pemetrexed and platinum had revealed promising efficacy for nonsquamous NSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to compare the efficacy and safety of sintilimab with placebo, both in combination with such chemotherapy (ClinicalTrials.gov: NCT03607539).
METHODS
A total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC without sensitizing EGFR or anaplastic lymphoma kinase genomic aberration were randomized (2:1 ratio) to receive either sintilimab 200 mg or placebo plus pemetrexed and platinum once every 3 weeks for four cycles, followed by sintilimab or placebo plus pemetrexed therapy. Crossover or treatment beyond disease progression was allowed. The primary end point was progression-free survival (PFS) as judged by an independent radiographic review committee.
RESULTS
As of November 15, 2019, the median follow-up was 8.9 months. The median PFS was significantly longer in the sintilimab-combination group than that in the placebo-combination group (8.9 versus 5.0 mo; hazard ratio, 0.482, 95% confidence interval [CI]: 0.362-0.643; p < 0.00001). The confirmed objective response rate was 51.9% (95% CI: 45.7%-58.0%) in the sintilimab-combination group and 29.8% (95% CI: 22.1%-38.4%) in placebo-combination group. The incidence of grade 3 or higher adverse events was 61.7% in sintilimab-combination group and 58.8% in placebo-combination group.
CONCLUSIONS
In Chinese patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC, the addition of sintilimab to chemotherapy with pemetrexed and platinum resulted in considerably longer PFS than with chemotherapy alone with manageable safety profiles.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Humans; Lung Neoplasms; Pemetrexed; Platinum
PubMed: 32781263
DOI: 10.1016/j.jtho.2020.07.014 -
JAMA Oncology Mar 2024The combination of an antibody to programmed cell death-1 (PD-1) or to its ligand (PD-L1) with chemotherapy is the standard first-line treatment for metastatic non-small... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The combination of an antibody to programmed cell death-1 (PD-1) or to its ligand (PD-L1) with chemotherapy is the standard first-line treatment for metastatic non-small cell lung cancer (NSCLC). Bevacizumab is expected to enhance the efficacy not only of chemotherapy but also of PD-1/PD-L1 antibodies through blockade of vascular endothelial growth factor-mediated immunosuppression, but further data are needed to support this.
OBJECTIVE
To evaluate the efficacy and safety of bevacizumab administered with platinum combination therapy and atezolizumab in patients with advanced nonsquamous NSCLC.
DESIGN, SETTING, AND PARTICIPANTS
An open-label phase 3 randomized clinical trial was conducted at 37 hospitals in Japan. Patients with advanced nonsquamous NSCLC without genetic driver alterations or those with genetic driver alterations who had received treatment with at least 1 approved tyrosine kinase inhibitor were enrolled between January 20, 2019, and August 12, 2020.
INTERVENTIONS
Patients were randomly assigned to receive either atezolizumab plus carboplatin with pemetrexed (APP) or atezolizumab, carboplatin plus pemetrexed, and bevacizumab (APPB). After 4 cycles of induction therapy, maintenance therapy with atezolizumab plus pemetrexed or with atezolizumab, pemetrexed, and bevacizumab was administered until evidence of disease progression, development of unacceptable toxic effects, or the elapse of 2 years from the initiation of protocol treatment.
MAIN OUTCOMES AND MEASURES
The primary end point was progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the intention-to-treat (ITT) population.
RESULTS
A total of 412 patients were enrolled (273 men [66%]; median age, 67.0 [range, 24-89] years) and randomly assigned, with 205 in the APPB group and 206 in the APP group of the ITT population after exclusion of 1 patient for good clinical practice violation. The median BICR-assessed PFS was 9.6 months with APPB vs 7.7 months with APP (stratified hazard ratio [HR], 0.86; 95% CI, 0.70-1.07; 1-sided stratified log-rank test; P = .92). According to prespecified subgroup analysis of BICR-assessed PFS, an improved PFS with APPB vs APP was apparent specifically in driver oncogene-positive patients (median, 9.7 vs 5.8 months; stratified HR, 0.67; 95% CI, 0.46-0.98). Toxic effects related to bevacizumab were increased in the APPB group.
CONCLUSIONS AND RELEVANCE
The findings of this trial did not show superiority of APPB over APP for patients with nonsquamous NSCLC; however, this regimen showed a similar tolerability and improved survival relative to APP in patients with driver oncogenes.
TRIAL REGISTRATION
Japan Registry of Clinical Trials Identifier: jRCT2080224500.
Topics: Aged; Humans; Male; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Bevacizumab; Carboplatin; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Pemetrexed; Platinum; Programmed Cell Death 1 Receptor; Vascular Endothelial Growth Factor A; Female; Young Adult; Adult; Middle Aged; Aged, 80 and over
PubMed: 38127362
DOI: 10.1001/jamaoncol.2023.5258 -
Cancer Science Aug 2021Pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) with manageable safety compared with placebo plus... (Randomized Controlled Trial)
Randomized Controlled Trial
Pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) with manageable safety compared with placebo plus pemetrexed-platinum in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations in the global, randomized, double-blind, phase 3 KEYNOTE-189 study. We present results of Japanese patients enrolled in the KEYNOTE-189 global and Japan extension studies. Patients were randomized 2:1 to intravenous pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for up to 35 cycles. All patients received pemetrexed 500 mg/m plus the investigator's choice of cisplatin or carboplatin Q3W for four cycles, followed by maintenance pemetrexed 500 mg/m Q3W (all intravenous). Co-primary endpoints were OS and PFS. Forty Japanese patients enrolled (pembrolizumab, n = 25; placebo, n = 15). At data cutoff (20 May 2019; median time from randomization to data cutoff, 18.5 [range, 14.7-38.2] months), the median OS was not reached in the pembrolizumab plus pemetrexed-platinum arm; the median OS was 25.9 (95% confidence interval [CI], 11.9-29.0) months in the placebo plus pemetrexed-platinum arm (hazard ratio [HR] .29; 95% CI, .07-1.15). The median (95% CI) PFS was 16.5 (8.8-21.1) compared with 7.1 (4.7-21.4) months (HR, .62; 95% CI, .27-1.42), respectively. There were no grade 5 adverse events (AE). Grade 3/4 AE occurred in 72% vs 60% of patients in the pembrolizumab vs placebo arms; 40% vs 20% had immune-mediated AE, and 4% vs 0% had infusion reactions. Efficacy and safety outcomes were similar to those from the global study and support first-line therapy with pembrolizumab plus pemetrexed-platinum in Japanese patients with nonsquamous NSCLC without EGFR/ALK alterations.
Topics: Administration, Intravenous; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Double-Blind Method; Humans; Japan; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pemetrexed; Platinum; Progression-Free Survival; Treatment Outcome
PubMed: 34036692
DOI: 10.1111/cas.14980 -
Signal Transduction and Targeted Therapy Oct 2021This multicenter phase-II trial aimed to investigate the efficacy, safety, and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in... (Randomized Controlled Trial)
Randomized Controlled Trial
This multicenter phase-II trial aimed to investigate the efficacy, safety, and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC. Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled. Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles, followed by the maintenance of toripalimab and pemetrexed. The primary endpoint was objective-response rate (ORR). Integrated biomarker analysis of PD-L1 expression, tumor mutational burden (TMB), CD8 + tumor-infiltrating lymphocyte (TIL) density, whole-exome, and transcriptome sequencing on tumor biopsies were also conducted. Forty patients were enrolled with an overall ORR of 50.0% and disease-control rate (DCR) of 87.5%. The median progression free survival (PFS) and overall survival were 7.0 and 23.5 months, respectively. The most common treatment-related adverse effects were leukopenia, neutropenia, anemia, ALT/AST elevation, and nausea. Biomarker analysis showed that none of PD-L1 expression, TMB level, and CD8 + TIL density could serve as a predictive biomarker. Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type. Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC. DSPP mutation might serve as a potential biomarker for this combination. A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing (NCT03924050).
Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Mutation; Pemetrexed; Progression-Free Survival; Protein Kinase Inhibitors; Young Adult
PubMed: 34650034
DOI: 10.1038/s41392-021-00751-9 -
Lung Cancer (Amsterdam, Netherlands) Sep 2022In ORIENT-11, first-line sintilimab + pemetrexed-platinum significantly improved PFS compared with placebo + pemetrexed-platinum in patients with advanced metastatic... (Randomized Controlled Trial)
Randomized Controlled Trial
Final overall survival data of sintilimab plus pemetrexed and platinum as First-Line treatment for locally advanced or metastatic nonsquamous NSCLC in the Phase 3 ORIENT-11 study.
OBJECTIVES
In ORIENT-11, first-line sintilimab + pemetrexed-platinum significantly improved PFS compared with placebo + pemetrexed-platinum in patients with advanced metastatic nonsquamous non-small-cell lung cancer (AMnsqNSCLC). The study met the primary endpoint of PFS as of 15November2019. Here we report final survival analysis from ORIENT-11 (NCT03607539) using a 15September2021 data cutoff.
METHODS
Patients with treatment-naïve locally AMnsqNSCLC without sensitizing EGFR or ALK genomic tumor aberrations were randomly assigned to sintilimab + pemetrexed-platinum (n = 266) or placebo + pemetrexed-platinum (n = 131). Patients were stratified by PD-L1 expression, platinum-chemotherapy, and gender. Treatment continued until PD, unacceptable toxicity, or a maximum of 24 months. Patients in the placebo + pemetrexed-platinum arm could be sequenced to second-line sintilimab monotherapy, contingent upon PD. Response was assessed (RECISTv.1.1) by blinded independent radiographic review committee. Primary endpoint was PFS. OS was a secondary endpoint and defined from date of randomization to date of death due to any cause. Final OS analysis was defined as approximately 2 years after last patient randomized or when approximately 65 % of patients died, whichever first.
RESULTS
At data cutoff of final OS analysis, median study follow-up was 30.8 months. Of 397 patients, 243 OS events were observed (sintilimab + pemetrexed-platinum:151[57 %];placebo + pemetrexed-platinum:92 [70 %]). Of the patients in placebo + pemetrexed-platinum arm, 47 % crossed over to sintilimab monotherapy per protocol. Median OS was 24.2 months in sintilimab + pemetrexed-platinum arm and 16.8 months in placebo + pemetrexed-platinum arm (HR:0.65[95 % CI:0.50,0.85]). Estimated 2-year OS rates were 50 %(sintilimab + pemetrexed-platinum) and 32 %(placebo + pemetrexed-platinum). After adjusting for the crossover effect, OS treatment effect was more pronounced with HR 0.52 (95 % CI:0.38,0.69). OS benefit across all prespecified subgroups was largely consistent with that observed in the ITT population.
CONCLUSIONS
In the ORIENT-11 final OS analysis, sintilimab + pemetrexed-platinum demonstrated improved OS compared to placebo + pemetrexed-platinum when administered as first-line therapy in AMnsqNSCLC without EGFR or ALK genomic tumor aberrations.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Pemetrexed; Platinum; Receptor Protein-Tyrosine Kinases
PubMed: 35917647
DOI: 10.1016/j.lungcan.2022.07.013 -
Journal of Clinical Oncology : Official... Jan 2020Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor combined with cytotoxic chemotherapy is highly effective for the treatment of advanced non-small-cell... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor combined with cytotoxic chemotherapy is highly effective for the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations; however, little is known about the efficacy and safety of this combination compared with that of standard therapy with EGFR- tyrosine kinase inhibitors alone.
METHODS
We randomly assigned 345 patients with newly diagnosed metastatic NSCLC with EGFR mutations to gefitinib combined with carboplatin plus pemetrexed or gefitinib alone. Progression-free survival (PFS), PFS2, and overall survival (OS) were sequentially analyzed as primary end points according to a hierarchical sequential testing method. Secondary end points were objective response rate (ORR), safety, and quality of life.
RESULTS
The combination group demonstrated a better ORR and PFS than the gefitinib group (ORR, 84% 67% [ < .001]; PFS, 20.9 11.9 months; hazard ratio for death or disease progression, 0.490 [ < .001]), although PFS2 was not significantly different (20.9 18.0 months; = .092). Median OS in the combination group was also significantly longer than in the gefitinib group (50.9 38.8 months; hazard ratio for death, 0.722; = .021). The rate of grade ≥ 3 treatment-related adverse events, such as hematologic toxicities, in the combination group was higher than in the gefitinib group (65.3% 31.0%); there were no differences in quality of life. One treatment-related death was observed in the combination group.
CONCLUSION
Compared with gefitinib alone, gefitinib combined with carboplatin plus pemetrexed improved PFS in patients with untreated advanced NSCLC with EGFR mutations with an acceptable toxicity profile, although its OS benefit requires further validation.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Pemetrexed; Progression-Free Survival; Protein Kinase Inhibitors; Quality of Life; Survival Rate
PubMed: 31682542
DOI: 10.1200/JCO.19.01488 -
Journal of Clinical Oncology : Official... Apr 2024In the treatment of non-small-cell lung cancer (NSCLC) with a driver mutation, the role of anti-PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear.... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
In the treatment of non-small-cell lung cancer (NSCLC) with a driver mutation, the role of anti-PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase III study evaluates the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in or -mutated NSCLC that progressed before TKI therapy.
MATERIALS AND METHODS
We compared the clinical efficacy of ABCP followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC) followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS).
RESULTS
A total of 228 patients with activating mutation (n = 215) or translocation (n = 13) were enrolled from 16 sites in the Republic of Korea and randomly assigned at 2:1 ratio to either ABCP (n = 154) or PC arm (n = 74). The median follow-up duration was 26.1 months (95% CI, 24.7 to 28.2). Objective response rates (69.5% 41.9%, < .001) and median PFS (8.48 5.62 months, hazard ratio [HR], 0.62 [95% CI, 0.45 to 0.86]; = .004) were significantly better in the ABCP than PC arm. PFS benefit increased as PD-L1 expression increased, with an HR of 0.47, 0.41, and 0.24 for PD-L1 ≥1%, ≥10%, and ≥50%, respectively. Overall survival was similar between ABCP and PC arm (20.63 20.27 months, HR, 1.01 [95% CI, 0.69 to 1.46]; = .975). The safety profile of the ABCP arm was comparable with that previously reported, with no additional safety signals, but higher rates of treatment-related adverse events were observed compared with the PC arm.
CONCLUSION
To our knowledge, this study is the first randomized phase III study to demonstrate the clinical benefit of anti-PD-L1 antibody in combination with bevacizumab and chemotherapy in patients with or -mutated NSCLC who have progressed on relevant targeted therapy.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Bevacizumab; Carboplatin; Lung Neoplasms; B7-H1 Antigen; Pemetrexed; ErbB Receptors; Receptor Protein-Tyrosine Kinases; Antineoplastic Combined Chemotherapy Protocols; Antibodies, Monoclonal, Humanized
PubMed: 37861993
DOI: 10.1200/JCO.23.01891 -
Journal of Thoracic Oncology : Official... May 2023In CameL phase 3 study (ClinicalTrials.gov: NCT03134872), addition of camrelizumab to first-line chemotherapy significantly improved the progression-free survival in... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
In CameL phase 3 study (ClinicalTrials.gov: NCT03134872), addition of camrelizumab to first-line chemotherapy significantly improved the progression-free survival in patients with stages IIIB to IV nonsquamous NSCLC. Here, we present outcomes after a minimum follow-up of 43.9 months since last patient randomization.
METHODS
Eligible patients were randomized 1:1 to 4 to 6 cycles of camrelizumab plus carboplatin and pemetrexed or chemotherapy alone every 3 weeks, followed by maintenance camrelizumab plus pemetrexed or pemetrexed only (n = 205 and 207, respectively). Total camrelizumab exposure was up to 2 years.
RESULTS
As of January 31, 2022, camrelizumab plus chemotherapy exhibited substantially improved overall survival over chemotherapy alone (median, 27.1 versus 19.8 mo; hazard ratio = 0.72 [95% confidence interval: 0.57-0.92]). In the chemotherapy-alone group, 95 patients (45.9%) crossed over to camrelizumab monotherapy. After adjustment for crossover, the survival benefit with camrelizumab plus chemotherapy was more pronounced (adjusted hazard ratio = 0.55 [95% confidence interval: 0.42-0.71]). In camrelizumab plus chemotherapy group, 33 patients completed 2 years of camrelizumab. Objective response rate was 97.0%, with ongoing responses in 17 of the 32 responses (53.1%), and 93.9% (31 of 33) of the patients were alive at data cutoff. Safety profiles were consistent with the previous report, and no obvious evidence of cumulative toxicity was found with long exposure to camrelizumab.
CONCLUSIONS
Camrelizumab plus carboplatin and pemetrexed provides long-term survival benefit over chemotherapy, with manageable toxicity and remarkable and durable response in patients receiving 2 years of camrelizumab, further supporting camrelizumab combination as first-line treatment for advanced nonsquamous NSCLC.
Topics: Humans; Animals; Pemetrexed; Carboplatin; Camelus; Lung Neoplasms; Follow-Up Studies; Carcinoma, Non-Small-Cell Lung; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36646210
DOI: 10.1016/j.jtho.2022.12.017