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Real-world outcomes of first-line pembrolizumab plus pemetrexed-carboplatin for metastatic nonsquamous NSCLC at US oncology practices.

ABSTRACT: 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.

SUBMITTER: Velcheti V

PROVIDER: S-EPMC8080779 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceChemotherapy is a mainstay treatment of metastatic non-small cell lung cancer. However, little is known about the comparative risk of hospitalization associated with commonly used chemotherapy regimens.ObjectiveTo evaluate the real-world association of specific lung cancer chemotherapy regimens with measures of acute hospital care (primary objective) and survival (secondary objective).Design, setting, and participantsRetrospective, propensity-matched, cohort study using the Surveillance, Epidemiology, and End Results-Medicare linked data for cancer diagnoses between 2008 and 2013, with follow-up through 2014. Patients were Medicare beneficiaries 66 years of age or older receiving initial chemotherapy for treatment of stage IV, nonsquamous, non-small cell lung cancer. Analyses were performed between September 2017 and April 2018.ExposuresReceipt of chemotherapy with carboplatin-pemetrexed or carboplatin-paclitaxel, with or without concurrent bevacizumab.Main outcomes and measuresThe primary outcome was risk of hospitalization within 30 days of chemotherapy initiation. Secondary measures included cumulative 90-day hospitalizations, 90-day mean hospital-free survival time, and overall survival.ResultsOf the 3310 eligible patients, 1823 received carboplatin-pemetrexed, and 1487 received carboplatin-paclitaxel. The median age at diagnosis was 73 years (interquartile range, 69-77 years), 1784 patients (53.9%) were men, and 2909 patients (87.9%) were non-Hispanic white. In total, 2182 patients were included in the propensity-matched analysis. The 30-day hospitalization risk was 20.7% (95% CI, 18.3%-23.1%) among patients receiving carboplatin-pemetrexed vs 26.0% (95% CI, 23.4%-28.6%) among patients receiving carboplatin-paclitaxel (5.3% difference; P?=?.003). The 90-day cumulative hospitalizations did not differ significantly between the 2 treatment groups; however, the 90-day mean hospital-free survival time was improved for patients receiving carboplatin-pemetrexed (68.4 days [95% CI, 66.5-70.4 days] vs 63.6 days [95% CI, 61.6-65.7 days]; P?=?.001). The median survival time was 9.0 months (95% CI, 8.4-9.5 months) with carboplatin-pemetrexed therapy vs 7.6 months (95% CI, 7.0-8.4 months) with carboplatin-paclitaxel therapy (P?=?.005). Stratified analyses showed no association of bevacizumab use with hospitalization risk or survival when combined with either chemotherapy regimen.Conclusions and relevanceThe findings from this study suggest that patients receiving carboplatin-pemetrexed compared with those receiving carboplatin-paclitaxel have a lower 30-day hospitalization risk, a greater 90-day hospital-free survival, and improved overall survival. Information about hospitalization risk may provide valuable context for evaluating real-world cancer treatment outcomes.

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.

Project description:ImportanceFew clinical trials have been specifically designed for elderly patients with advanced non-small cell lung cancer (NSCLC), and the anticipated increase in the number of such patients has prompted a search for new treatment options that provide a greater palliative benefit.ObjectiveTo determine whether treatment with carboplatin plus pemetrexed followed by pemetrexed maintenance is noninferior compared with docetaxel monotherapy with regard to overall survival (OS) for elderly patients with advanced nonsquamous NSCLC.Design, setting, and participantsThis open-label, multicenter, noninferiority phase 3 randomized clinical trial was conducted at 79 institutions in Japan. Cytotoxic chemotherapy-naive patients with advanced nonsquamous NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and age of 75 years or older were enrolled between August 2013 and February 2017. Data were analyzed from November 2018 to February 2019.InterventionsPatients were randomized to receive either docetaxel monotherapy (60 mg/m2) every 3 weeks or 4 cycles of carboplatin (area under the curve of 5) plus pemetrexed (500 mg/m2) administered every 3 weeks followed by maintenance therapy with the same dose of pemetrexed for 3 weeks.Main outcomes and measuresThe primary end point was OS analyzed on an intention-to-treat basis with a noninferiority margin of 1.154 for the upper limit of the 95% CI of the hazard ratio (HR) estimated with a stratified Cox regression model.ResultsOf the 433 enrolled patients, 250 (57.7%) were male, and the median (range) age was 78 (75-88) years. The median OS was 15.5 months (95% CI, 13.6-18.4) in the docetaxel group (n?=?217) and 18.7 months (95% CI, 16.0-21.9) in the carboplatin-pemetrexed group (n?=?216), with a stratified HR for OS of 0.850 (95% CI, 0.684-1.056; P for noninferiority?=?.003). Progression-free survival was also longer in the carboplatin-pemetrexed group (unstratified HR, 0.739; 95% CI, 0.609-0.896). Compared with those in the docetaxel group, those in the carboplatin-pemetrexed had lower rates of leukopenia (60 of 214 [28.0%] vs 147 of 214 [68.7%]) and neutropenia (99 of 214 [46.3%] vs 184 of 214 [86.0%]) of grade 3 or 4 and of febrile neutropenia (9 of 214 [4.2%] vs 38 of 214 [17.8%]) and higher rates of thrombocytopenia (55 of 214 [25.7%] vs 3 of 214 [1.4%]) and anemia (63 of 214 [29.4%] vs 4 of 214 [1.9%]) of grade 3 or 4. Dose reductions were less frequent with carboplatin-pemetrexed.Conclusion and relevanceCarboplatin-pemetrexed treatment followed by pemetrexed maintenance is a valid option for first-line treatment of elderly patients with advanced nonsquamous NSCLC.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000011460.

Project description:BackgroundMany physicians consider platinum-doublet chemotherapy inappropriate for elderly patients, regardless of their medical fitness.ObjectiveThis was a retrospective subgroup analysis of data from a multicenter, randomized, phase III clinical trial evaluating pemetrexed + carboplatin versus docetaxel + carboplatin in elderly chemo-naive patients with advanced, nonsquamous non-small cell lung cancer (NSCLC).MethodsData from elderly patients (aged ≥65 years and ≥70 years) were evaluated using the same statistical methods as those used in patients aged <70 years and qualified intent-to-treat (Q-ITT) populations. The primary objective of the clinical trial was comparison of pemetrexed + carboplatin with docetaxel + carboplatin in terms of survival without grade 3 or 4 toxicity in chemo-naive NSCLC patients.ResultsThe ≥65- and ≥70-year age groups had 68 and 37 patients, respectively. Among patients aged ≥65 years, the adjusted hazard ratio (HR) for survival without grade 3-4 toxicity (HR 0.40, 95 % confidence interval [CI] 0.23-0.70) favored pemetrexed + carboplatin; this was similar to the HRs in patients aged ≥70 years (HR 0.43, 95 % CI 0.20-0.92), patients aged <70 years (HR 0.44, 95 % CI 0.32-0.62), and the Q-ITT population (HR 0.45, 95 % CI 0.34-0.61). The median values for overall survival (OS) and progression-free survival (PFS) were similar across all age-group subsets and the Q-ITT population. The HRs for OS and PFS were similar for all age-group subsets, except for the ≥70-year age group, which favored pemetrexed + carboplatin to a greater extent. The toxicity profile was similar across age groups, with the exception of diarrhea, mucosal inflammation, and grade 3-4 neutropenia and leukopenia, which were slightly more common in elderly patients in both treatment arms. Between-arm differences in the toxicity profiles for the ≥65-, ≥70- and <70-year age subgroups were similar to those in the Q-ITT population. There were no on-study deaths or unexpected toxicities.ConclusionThe benefits of pemetrexed + carboplatin were maintained, and toxicity was manageable in both elderly subgroups. The favorable risk-benefit profile of pemetrexed + carboplatin makes it an appropriate first-line treatment option for elderly patients with advanced nonsquamous NSCLC.

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Real-world outcomes of first-line pembrolizumab plus pemetrexed-carboplatin for metastatic nonsquamous NSCLC at US oncology practices.

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