An extended overall survival analysis of pemetrexed and carboplatin with or without pembrolizumab as first-line therapy for advanced non-squamous non-small cell lung cancer.
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SUBMITTER: Afzal MZ
PROVIDER: S-EPMC6462590 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer.MethodsCAP29 is a retrospective, observational, multicenter real-life study conducted in 6 French centers. We evaluated efficacy of first-line setting chemotherapy plus pembrolizumab (November 2019 to September 2020) in advanced (stage III-IV) non-squamous non-small cell lung cancer patients without targetable alterations. Primary endpoint was progression-free survival. Secondary endpoints were overall survival, objective response rate and safety.ResultsWith a median follow-up of 4.5 months (0 to 22 months), a total of 121 patients were included. Baseline characteristics were: median age of 59.8 years with 7.4% ≥75 years, 58.7% of males, 91.8% PS 0-1, 87.6% of stage IV with ≥3 metastatic sites in 62% of cases. Patients had brain and liver metastases in 24% and 15.7% of cases, respectively. PD-L1 was <1% (44.6%), 1-49% (28.1%) and ≥50% (21.5%). Median progression-free survival and overall survival achieved 9 and 20.6 months, respectively. Objective response rate was 63.7% with 7 prolonged complete responses. Survival benefit seemed to be correlated with PD-L1 expression. Brain and liver metastases were not statistically associated with decreased overall survival. Most common adverse events were asthenia (76%), anemia (61.2%), nausea (53.7%), decreased appetite (37.2%) and liver cytolysis (34.7%). Renal and hepatic disorders were the main causes of pemetrexed discontinuation. Grade 3-4 adverse events concerned 17.5% of patients. Two treatment-related deaths were reported.ConclusionsFirst-line pembrolizumab plus chemotherapy confirmed real-life efficacy for patients with advanced non-squamous non-small cell lung cancer. With median progression-free survival and overall survival of 9.0 and 20.6 months, respectively and no new safety signal, our real-life data are very close to results provided by clinical trials, confirming the benefit and the manageable toxicity profile of this combination.
| S-EPMC9989798 | biostudies-literature
Project description:BackgroundLimited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer (NSCLC) setting. The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy. We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC.MethodsIn this randomised, open-label, phase 2 cohort of a multicohort study (KEYNOTE-021), patients were enrolled at 26 medical centres in the USA and Taiwan. Patients with chemotherapy-naive, stage IIIB or IV, non-squamous NSCLC without targetable EGFR or ALK genetic aberrations were randomly assigned (1:1) in blocks of four stratified by PD-L1 tumour proportion score (<1% vs ≥1%) using an interactive voice-response system to 4 cycles of pembrolizumab 200 mg plus carboplatin area under curve 5 mg/mL per min and pemetrexed 500 mg/m2 every 3 weeks followed by pembrolizumab for 24 months and indefinite pemetrexed maintenance therapy or to 4 cycles of carboplatin and pemetrexed alone followed by indefinite pemetrexed maintenance therapy. The primary endpoint was the proportion of patients who achieved an objective response, defined as the percentage of patients with radiologically confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by masked, independent central review, in the intention-to-treat population, defined as all patients who were allocated to study treatment. Significance threshold was p<0·025 (one sided). Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned study treatment. This trial, which is closed for enrolment but continuing for follow-up, is registered with ClinicalTrials.gov, number NCT02039674.FindingsBetween Nov 25, 2014, and Jan 25, 2016, 123 patients were enrolled; 60 were randomly assigned to the pembrolizumab plus chemotherapy group and 63 to the chemotherapy alone group. 33 (55%; 95% CI 42-68) of 60 patients in the pembrolizumab plus chemotherapy group achieved an objective response compared with 18 (29%; 18-41) of 63 patients in the chemotherapy alone group (estimated treatment difference 26% [95% CI 9-42%]; p=0·0016). The incidence of grade 3 or worse treatment-related adverse events was similar between groups (23 [39%] of 59 patients in the pembrolizumab plus chemotherapy group and 16 [26%] of 62 in the chemotherapy alone group). The most common grade 3 or worse treatment-related adverse events in the pembrolizumab plus chemotherapy group were anaemia (seven [12%] of 59) and decreased neutrophil count (three [5%]); an additional six events each occurred in two (3%) for acute kidney injury, decreased lymphocyte count, fatigue, neutropenia, and sepsis, and thrombocytopenia. In the chemotherapy alone group, the most common grade 3 or worse events were anaemia (nine [15%] of 62) and decreased neutrophil count, pancytopenia, and thrombocytopenia (two [3%] each). One (2%) of 59 patients in the pembrolizumab plus chemotherapy group experienced treatment-related death because of sepsis compared with two (3%) of 62 patients in the chemotherapy group: one because of sepsis and one because of pancytopenia.InterpretationCombination of pembrolizumab, carboplatin, and pemetrexed could be an effective and tolerable first-line treatment option for patients with advanced non-squamous NSCLC. This finding is being further explored in an ongoing international, randomised, double-blind, phase 3 study.FundingMerck & Co.
| S-EPMC6886237 | biostudies-literature
Project description:Chemotherapy with pemetrexed plus carboplatin followed by pemetrexed maintenance therapy is a first-line regimen for patients with advanced non-squamous non-small-cell lung cancer. This phase II clinical study investigated the efficacy and safety of this regimen in older patients (aged ?65 years) with advanced non-squamous non-small-cell lung cancer. All patients received 4 courses of induction therapy with pemetrexed (500 mg/m2) combined with carboplatin once every 3 weeks. If patients had stable disease or achieved a complete or partial tumor response after 4 courses of pemetrexed + carboplatin therapy, maintenance treatment with pemetrexed monotherapy was administered until either disease progression or intolerable toxicity occurred. The primary endpoint was progression-free survival, while secondary endpoints were the objective response rate, overall survival, and tolerability. A total of 105 elderly patients (median age, 71 years) with advanced lung adenocarcinoma were enrolled in the trial. The ORR with induction therapy was 36.2% and the disease control rate was 70.5%. Sixty-two patients (59.0%) subsequently received pemetrexed maintenance therapy. The median progression-free survival for all patients was 8.23 months (95% CI 5.85-10.62 months) and the median overall survival was 22.6 months (95% CI 20.09-25.11 months). Grade 3 or greater toxicities included neutropenia (15.3%), thrombocytopenia (9.5%), anemia (8.6%), leukopenia (4.8%), nausea (1.0%), vomiting (1.0%), and fatigue (1.0%). No treatment-related deaths occurred. These results indicate that pemetrexed combined with carboplatin therapy maintained by single-agent pemetrexed treatment of elderly patients with advanced non-squamous non-small-cell lung cancer was effective and tolerable. ClinicalTrials.gov identifier: NCT01860508.
| S-EPMC5689692 | biostudies-literature
Project description:BACKGROUND:The study was conducted to compare the effectiveness and safety of pemetrexed/carboplatin or cisplatin/bevacizumab (PemPBev) and paclitaxel/carboplatin/bevacizumab (PacCBev) as first-line therapy for advanced non-squamous non-small cell lung cancer (NS-NSCLC) patients with wild-type driver genes in a real-world setting. METHODS:We retrospectively collected the medical records of advanced NS-NSCLC patients with wild-type driver genes administered first-line PemPBev or PacCBev therapy at Shanghai Chest Hospital between January 2014 and June 2016, and analyzed the differences in survival outcomes, efficacy, and safety between PemPBev and PacCBev treatment. RESULTS:A total of 390 patients were included in our analysis: 249 in the PemPBev group and 141 in the PacCBev group. Patients administered PemPBev experienced significantly improved progression-free survival (PFS) and overall survival (OS) compared to those administered PacCBev (PFS 7.5 vs. 6.2?months, hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.53-0.84, P <?0.001; OS:18.6 vs. 16.0?months, HR?0.68, 95% CI 0.52-0.90, P =?0.002). The objective response rate (ORR) and disease control rate (DCR) were similar between the groups (ORR 21.7% vs. 30.5%, P?=?0.053; DCR 69.1% vs. 67.4%, P =?0.728). There was no significant difference in the incidence of adverse events between the groups (64.7% vs. 68.8%; P =?0.407), but the incidence of peripheral neuropathy in the PacCBev group was higher than in the PemPBev group (7.8% vs. 2.4%; P =?0.012). CONCLUSION:Our study shows that for advanced NS-NSCLC patients with wild-type driver genes, first-line PemPBev might be a better treatment option compared to PacCBev.
| S-EPMC6501044 | biostudies-literature
Project description:BackgroundOur prospective, open-label, single-arm phase II study investigated the safety and efficacy of DCVAC/LuCa (dendritic cell vaccines for lung cancer) combined with standard carboplatin/pemetrexed in advanced non-squamous (nsq) non-small-cell lung cancer (NSCLC).Patients and methodsEligible patients had stage IV nsq NSCLC without oncogenic drivers and had not received prior systemic cancer therapy. Treatment consisted of carboplatin/pemetrexed for up to 6 cycles followed by 21 cycles of pemetrexed maintenance or until progression or intolerance. Non-progression patients after two cycles of chemotherapy started to receive DCVAC/LuCa subcutaneously (s.c.) on day 15 of cycle 3, and thereafter q3w (day 15 of chemotherapy cycles) for up to 15 doses. Dosing of DCVAC/LuCa s.c. varied among patients depending on the baseline number of leucocytes but remained constant for each single patient. Safety was assessed by adverse events (AEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). Efficacy was measured by overall survival (OS), progression-free survival (PFS), time to progression (TTP), and objective response rate (ORR).ResultsSixty-one patients were enrolled. In the safety population (n = 60), eight patients (13.33%) had grade 3 or greater TRAEs, and six patients (10.0%) showed SAEs which were not related to leukapheresis or DC vaccination. Six grade 1 AEs were considered to be related to leukapheresis. No AESIs or DCVAC/LuCa-induced AEs were observed. The 2-year survival rate in the modified intention-to-treat population (n = 44) was 52.57%. Median OS was not reached. Median PFS was 8.0 months, median TTP was 10.2 months, and the ORR was 31.82%.ConclusionIn treatment-naïve stage IV nsq NSCLC patients without oncogenic drivers, the combination of carboplatin/pemetrexed and DCVAC/LuCa was well tolerated and showed promising efficacy. Therefore, a study to prove our immunotherapeutic concept in a randomized phase III trial is planned.
| S-EPMC8718955 | biostudies-literature
Project description:Evidence from real-world clinical settings is lacking with regard to first-line immunotherapy plus chemotherapy for the treatment of non-small cell lung cancer (NSCLC). Our aim was to describe outcomes for patients treated with first-line pembrolizumab-combination therapy for metastatic nonsquamous NSCLC in US oncology practices. Using an anonymized, nationwide electronic health record-derived database, we identified patients who initiated pembrolizumab plus pemetrexed-carboplatin in the first-line setting (May 2017 to August 2018) after diagnosis of metastatic nonsquamous NSCLC that tested negative for EGFR and ALK genomic aberrations. Eligible patients had ECOG performance status of 0-1. An enhanced manual chart review was used to collect outcome information. Time-to-event analyses were performed using the Kaplan-Meier method. Of 283 eligible patients, 168 (59%) were male; median age was 66 years (range 33-84); and the proportions of patients with PD-L1 tumor proportion score (TPS) of ≥ 50%, 1-49%, < 1%, and unknown were 28%, 27%, 28%, and 17%, respectively. At data cutoff on August 31, 2019, median patient follow-up was 20.3 months (range 12-28 months), and median real-world times on treatment (rwToT) with pembrolizumab and pemetrexed were 5.6 (95% CI 4.5-6.4) and 2.8 months (95% CI 2.2-3.5), respectively. Median overall survival (OS) was 16.5 months (95% CI 13.2-20.6); estimated 12-month survival was 59.5% (95% CI 53.3-65.0); rwProgression-free survival was 6.4 months (95% CI 5.4-7.8); and rwTumor response rate (complete or partial response) was 56.5% (95% CI 50.5-62.4). Median OS was 20.6, 16.3, 13.2, and 13.7 months for patient cohorts with PD-L1 TPS ≥ 50%, 1-49%, < 1%, and unknown, respectively. These findings demonstrate the effectiveness of pembrolizumab plus pemetrexed-carboplatin by describing clinical outcomes among patients with metastatic nonsquamous NSCLC who were treated at US oncology practices.
| S-EPMC8080779 | biostudies-literature
Project description:IntroductionPRONOUNCE compared the efficacy and safety of pemetrexed+carboplatin followed by pemetrexed (Pem+Cb) with paclitaxel+carboplatin+bevacizumab followed by bevacizumab (Pac+Cb+Bev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC).MethodsPatients ≥18 years of age with stage IV nonsquamous NSCLC (American Joint Committee on Cancer v7.0), and Eastern Cooperative Oncology Group performance status 0/1 were randomized (1:1) to four cycles of induction Pem+Cb (pemetrexed, 500 mg/m, carboplatin, area under the curve = 6) followed by Pem maintenance or Pac+Cb+Bev (paclitaxel, 200 mg/m, carboplatin, area under the curve = 6, and bevacizumab, 15 mg/kg) followed by Bev maintenance in the absence of progressive disease or discontinuation. The primary objective was progression-free survival (PFS) without grade 4 toxicity (G4PFS). Secondary end points were PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety. Resource utilization was also assessed.ResultsBaseline characteristics of the patients randomized to Pem+Cb (N = 182) and Pac+Cb+Bev (N = 179) were well balanced between the arms. Median (months) G4PFS was 3.91 for Pem+Cb and 2.86 for Pac+Cb+Bev (hazard ratio = 0.85, 90% confidence interval, 0.7-1.04; p = 0.176); PFS, OS, ORR, or DCR did not differ significantly between the arms. Significantly more drug-related grade 3/4 anemia (18.7% versus 5.4%) and thrombocytopenia (24.0% versus 9.6%) were reported for Pem+Cb. Significantly more grade 3/4 neutropenia (48.8% versus 24.6%), grade 1/2 alopecia (28.3% versus 8.2%), and grade 1/2 sensory neuropathy were reported for Pac+Cb+Bev. Number of hospitalizations and overall length of stay did not differ significantly between the arms.ConclusionsPem+Cb did not produce significantly better G4PFS compared with Pac+Cb+Bev. Pem+Cb was not superior in PFS, OS, ORR, or DCR compared with Pac+Cb+Bev. Both regimens were well tolerated, although, toxicity profiles differed.
| S-EPMC4276572 | biostudies-literature
Project description:BackgroundThe role and timing of whole or stereotaxic brain radiotherapy (BR) in patients with advanced non-small cell lung cancer (aNSCLC) and asymptomatic brain metastases (aBMs) are not well established. This study investigates whether deferring BR until cerebral progression was superior to upfront BR for patients with aNSCLC and aBM.MethodsThis open-label, multicenter, phase III trial, randomized (1:1) aNSCLC patients with aBMs to receive upfront BR and chemotherapy: platin-pemetrexed and bevacizumab in eligible patients, followed by maintenance pemetrexed with or without bevacizumab, BR arm, or the same chemotherapy with BR only at cerebral progression, chemotherapy (ChT) arm. Primary endpoint was progression-free survival (PFS), secondary endpoints were overall survival (OS), global, extra-cerebral and cerebral objective response rate (ORR), toxicity, and quality of life [ClinicalTrials.gov identifier: NCT02162537].ResultsThe trial was stopped early because of slow recruitment. Among 95 included patients, 91 were randomized in 24 centers: 45 to BR and 46 to ChT arms (age: 60 ± 8.1, men: 79%, PS 0/1: 51.7%/48.3%; adenocarcinomas: 92.2%, extra-cerebral metastases: 57.8%, without differences between arms.) Significantly more patients in the BR-arm received BR compare with those in the ChT arm (87% versus 20%; p < 0.001); there were no significant differences between BR and ChT arms for median PFS: 4.7, 95% confidence interval (CI):3.4-7.5 versus 4.8, 95% CI: 2.4-6.5 months, for median OS: 8.5, 95% CI:.6-11.1 versus 8.3, 95% CI:4.5-11.5 months, cerebral and extra-cerebral ORR (27% versus 13%, p = 0.064, and 30% versus 41%, p = 0.245, respectively). The ChT arm had more grade 3/4 neutropenia than the BR arm (13% versus 6%, p = 0.045); others toxicities were comparable.ConclusionThe significant BR rate difference between the two arms suggests that upfront BR is not mandatory in aNSCLC with aBM but this trial failed to show that deferring BR for aBM is superior in terms of PFS from upfront BR.
| S-EPMC8053829 | biostudies-literature
Project description:Background:The aim of the study was to investigate in terms of noninferiority the efficacy and safety of a monochemotherapy regimen of pemetrexed plus bevacizumab (BevPem) versus carboplatin/pemetrexed plus bevacizumab (BevCPem) in elderly patients as first-line treatment for advanced metastatic or recurrent nonsquamous non-small-cell lung cancer (NSCLC). Materials and methods:65Plus was a Phase III, randomized, open-label study. In total, 253 patients received BevPem (n=119) or BevCPem (n=134). The primary outcome measure was progression-free survival. Secondary end points were overall survival, tumor response, and safety outcomes. Evaluations were performed for the whole study population and stratified according to Eastern Cooperative Oncology Group (ECOG) performance status (PS). Results:Noninferiority of BevPem in comparison to BevCPem could not be demonstrated for the overall population (P=0.7864). Significant superiority of the combined treatment BevCPem was seen in patients of ECOG PS 0-1 (median PFS 5.1 vs 6.9 months, HR 1.353, 95% CI 1.03-1.777), while the opposite tendency was observed in patients with ECOG PS 2 (median PFS 2.9 vs 1.5 months, HR 0.628, 95% CI 0.195-2.025). Overall, better tolerability was found for the BevPem group, irrespective of ECOG PS. Conclusion:Results from the 65plus study give evidence that BevPem and BevCPem treatments may exert differential effects on PFS, depending on the patients ECOG PS. It appears that patients with better ECOG PS (0-1) benefited more from the combined treatment with carboplatin, while the group comprising more severely impaired patients (ECOG PS 2) benefited more from the monochemotherapy.
| S-EPMC5683796 | biostudies-literature
Project description:ObjectiveTo evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance therapy with pemetrexed and bevacizumab (PB) in chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS) protein and mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).MethodsA cohort of 144 patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5.0 mg/ml/min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance PB was administered until disease progression or unacceptable toxicity.ResultsOne hundred forty-four Colombian patients with a median follow-up of 13.8 months and a median number of 6 maintenance cycles (range, 1-32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median PFS and (OS) rates were 7.9 months (95% CI, 5.9-10.0 months) and 21.4 months (95% CI, 18.3 to 24.4 months), respectively. We documented grade 3/4 hematologic toxicities, including anemia (14%), neutropenia (8%), and thrombocytopenia (16%). The identified grade 3/4 non-hematologic toxicities were proteinuria (2%), venous thrombosis (4%), fatigue (11%), infection (6%), nephrotoxicity (2%), and sensory neuropathy (4%). No grade >3 hemorrhagic events or hypertension cases were reported. OS was significantly higher in patients with the lowest TS mRNA levels [median, 29.6 months (95% CI, 26.2-32.9)] compared with those in patients with higher levels [median, 9.3 months (95% CI, 6.6-12.0); p = 0.0001]. TS expression (mRNA levels or protein expression) did not influence the treatment response.ConclusionOverall, PCB followed by maintenance pemetrexed and bevacizumab was effective and tolerable in Hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and prolonged OS, particularly in patients with low TS expression. We found a role for Ki67 and TS expression as prognostic factors.
| S-EPMC4871516 | biostudies-literature