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Efficacy of epidermal growth factor receptor inhibitors in combination with chemotherapy in advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.

ABSTRACT: The role of a combination of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy for non-small-cell lung cancer (NSCLC) has not been well established. To clarify this problem, we performed a meta-analysis with 15 studies identified from PubMed, EMBASE and the Cochrane Library. We found that the combined regimen had a significant benefit on progression-free survival (PFS) (hazard ratio (HR) = 0.80; 95% CI = 0.71-0.90; P < 0.001) and the objective response rate (ORR) (RR = 1.35; 95% CI = 1.14-1.59; P < 0.001). However, the combined regimen had no significant impact on overall survival (OS) (HR = 0.96; 95% CI = 0.90-1.03; P = 0.25). Subgroup analysis showed significantly higher OS advantages in EGFR mutation positive patients (P = 0.01), never smokers (P = 0.01), Asian patients (P = 0.02), patients receiving second-line treatment (P < 0.001), and those receiving a sequential combination of EGFR-TKIs and chemotherapy (P = 0.005). The combination regimen showed a higher incidence of grade 3-4 toxicities (leucopenia, neutropenia, febrile neutropenia, anemia, rash, fatigue and diarrhea). In summary, the combination of EGFR-TKIs plus chemotherapy in advanced NSCLC achieved a significantly longer PFS and a higher ORR but not longer OS. Well-designed prospective studies are needed to confirm these findings.

SUBMITTER: Zhang M

PROVIDER: S-EPMC5129973 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe ADAURA trial reported that osimertinib improved overall survival (OS) as an adjuvant chemotherapy for pathological stage IB-IIIA epidermal growth factor receptor (EGFR) mutant lung cancer compared with a placebo. Currently, platinum-based adjuvant chemotherapy is the standard treatment for patients with or without EGFR mutations. This study aimed to evaluate the efficacy of platinum-based adjuvant chemotherapy in patient with stage II-IIIA EGFR mutant lung adenocarcinoma.MethodsWe collected the medical records of consecutive patients who underwent surgical resection for lung adenocarcinoma between 2005 and 2012 at the four participating institutions. The data of 173 patients with different EGFR mutation status were retrospectively evaluated to determine the efficacy of platinum-based adjuvant chemotherapy for OS and recurrence-free survival (RFS). We further analyzed OS using the inverse probability of treatment weighting method with propensity scores.ResultsThe median age was 69 years (range, 45-85 years); 95 (54.9%) were male and 74 (42.8%) had EGFR mutations. A total of 43 patients with EGFR mutants (58.1%) and 43 patients with wild-type EGFR tumors (43.4%) received platinum-based adjuvant chemotherapy. No differences in RFS and OS were observed between EGFR mutant and wild-type EGFR in lung adenocarcinoma without adjuvant therapy. However, wild-type EGFR showed an improvement in OS with platinum-based adjuvant chemotherapy in inverse probability of treatment weighting analysis, whereas those with EGFR mutations showed no significant difference in OS between the surgery-only group and the adjuvant group. The deletion of exon 19 and exon 21 L858R point mutation showed no significant differences in OS between the surgery-only group and the adjuvant group, respectively. The hazard ratio (HR) exceeded 1 for uncommon EGFR mutations.ConclusionsPlatinum-based adjuvant chemotherapy may be less effective for EGFR-mutant lung adenocarcinoma, regardless of the mutation type.

Project description:Immune checkpoint inhibitors (ICIs) are recommended as first-line treatment for late-stage non-small cell lung cancer (NSCLC), either as monotherapy or in combination with chemotherapy. However, efficacy and safety comparisons between ICIs as monotherapy and ICIs with chemotherapy are lacking. We searched PubMed, Embase, and Cochrane Library for randomized controlled trials published before February 29th, 2020, with the search terms "immunotherapy" and "chemotherapy". 10 eligible trials were identified with a total of 5,956 patients. Of these patients, 3,204 received immune therapy and 2,752 received chemotherapy. PD-1 inhibitors with chemotherapy improved OS (HR 0.84, 0.77-0.92), PFS (HR 0.80, 0.75-0.85), and objective response rate (ORR) (odds ratio (OR) 2.55, 1.20-5.28) compared to PD-1 inhibitors as monotherapy. In contrast, PD-L1 inhibitors plus chemotherapy showed no significant differences in OS, PFS, or ORR compared with PD-L1 inhibitors as monotherapy. When patients were stratified according to PD-L1 expression level, patients with high PD-L1 expression (≥ 50%) receiving PD-1 inhibitors plus chemotherapy had improved PFS, but not other outcomes, compared to PD-1 inhibitors as monotherapy. In these patients, PD-L1 inhibitors plus chemotherapy showed no significant difference in survival compared with PD-L1 inhibitors. In the low PD-L1 expression group (1%-49%), PD-1 inhibitors plus chemotherapy improved OS and PFS, but no advantage was observed in PD-L1 inhibitors plus chemotherapy in OS, PFS, or ORR compared with PD-L1 inhibitor monotherapy. When comparing PD-1/PD-L1 inhibitors plus chemotherapy with PD-1/PD-L1 inhibitors monotherapy, no significant differences were observed in the rate of immune-related adverse events (AEs). In summary, for treating patients with late-stage NSCLC, PD-1 inhibitors plus chemotherapy have improved efficacy compared with PD-1 inhibitor monotherapy, but PD-L1 inhibitors plus chemotherapy have similar efficacy as PD-L1 monotherapy. Survival benefits of PD-1/PD-L1 inhibitors combined with chemotherapy were particularly significant in patients with low PD-L1 expression levels.Systematic review registrationPROSPERO, identifier CRD42020166678 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=166678).

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Efficacy of epidermal growth factor receptor inhibitors in combination with chemotherapy in advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.

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