Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: A Pairwise and Network Meta-Analysis of Pathological Complete Response.

We performed a pairwise and network meta-analysis to compare pathological complete response (pCR) among neoadjuvant chemotherapy in patients with triple-negative breast cancer. We searched PubMed for randomized clinical trials between January 1, 2000 and December 1, 2020. Abstracts from meetings were also searched. A frequentist random-effect model was applied to compare pCR and toxicities. The P-score was used to rank treatment effects. Nineteen trials with 16 treatments and 7794 patients were included. On the basis of SoC, the addition of carboplatin (OR = 1.82, 95% CI, 1.24 to 2.68, P < .01) and the addition of checkpoint inhibitors (OR = 1.69, 95% CI, 1.23 to 2.32, P < .01) increased pCR in pairwise meta-analysis; compared with paclitaxel, nab-paclitaxel did not improve pCR rates (OR = 1.81, 95% CI, .80 to 4.12, P = .16). The anthracycline-sparing regimen led to similar pCR compared with the anthracycline-containing regimen (OR = 1.50, 95% CI, .82 to 2.76, P = .19). In network meta-analysis, the addition of carboplatin plus a PD-1 inhibitor (pembrolizumab), carboplatin plus bevacizumab, and carboplatin plus veliparib ranked as the top three treatments for achieving pCR, with corresponding P-scores of .91, .84, and .72, respectively. Among patients with homologous recombination deficiency, the addition of carboplatin (OR = 1.31, 95% CI, .69 to 2.50, P = .41) or carboplatin plus PARP inhibitors (OR = 1.19, 95% CI, .58 to 2.47, P = .63) did not increase pCR. For triple-negative breast cancer, combining carboplatin with taxane-anthracycline-containing neoadjuvant chemotherapy could be the standard of care, and the combination containing checkpoint inhibitor is promising. However, their role in long-term oncologic outcome remains to be determined.

Front-line Therapy in Advanced Non-Small Cell Lung Cancer With Sensitive Epidermal Growth Factor Receptor Mutations: A Network Meta-analysis.

PURPOSE: Several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were firmly established as front-line treatment for non-small cell lung cancer (NSCLC) that harbored an activating EGFR mutation. Gefitinib or erlotinib was considered the standard of care. TKI-based combination therapy has been investigated and has shown encouraging results. METHODS: The PubMed and EMBASE databases, the Cochrane Central Register of Controlled Trials, and meeting abstracts were screened for relevant studies between January 2000 and February 2019. Prospective randomized controlled trials were included that investigated EGFR TKIs (alone or in combination) in untreated patients with NSCLC whose tumors had sensitive EGFR mutations. A frequentist random effects network meta-analysis model was conducted to assess objective response rate, progression-free survival, and overall survival. P-score was used to rank treatment effects. FINDINGS: Seventeen trials involving 9 treatments and 4373 patients were included. Heterogeneity existed in the network analysis. For progression-free survival, the top 3 treatments were osimertinib, standard of care plus chemotherapy, and standard of care plus bevacizumab; corresponding p-scores were 0.88, 0.79, and 0.75, respectively. For overall survival, the top 3 treatments were standard of care plus chemotherapy, osimertinib, and dacomitinib; corresponding p-scores were 0.89, 0.85, and 0.64. TKI-based combination therapy caused more toxicity than a TKI alone. IMPLICATIONS: Osimertinib seemed to be a better option as upfront therapy for EGFR-mutant NSCLC in terms of efficacy and tolerability.

First-line checkpoint inhibitors for wild-type advanced non-small-cell cancer: a pair-wise and network meta-analysis.

AIM: To estimate efficacy of checkpoint inhibitors and rank treatment effects in non-small-cell lung cancer. MATERIALS & METHODS: Prospective randomized trials were included. p-score was used to rank treatment effects. RESULTS: A total of nine trials were identified, involving 5504 patients and three checkpoint inhibitors. Pembrolizumab plus chemotherapy had the highest p-score of 0.95 among all the treatments, and was superior to pembrolizumab alone (hazard ratio: 0.87; 95% CI: 0.79-0.95). Combination therapy had more grade 3-5 adverse events; but toxicity-related discontinuation and treatment-related death did not increase. CONCLUSION: Pembrolizumab plus chemotherapy was likely to be the most effective treatment for patients with wild-type advanced NSCLC.

CDK4/6 inhibition versus mTOR blockade as second-line strategy in postmenopausal patients with hormone receptor-positive advanced breast cancer: A network meta-analysis.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib and abemaciclib) and mammalian target of rapamycin (mTOR) inhibitors (everolimus) are effective agents for restoring endocrine sensitivity in patients with advanced breast cancer progression on prior aromatase inhibitors. We conducted a network meta-analysis to compare these treatments in terms of progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). METHODS: The PubMed and Embase databases were searched for relevant publications between January 2000 and June 2018. Treatments were ranked based on a network meta-analysis. Ranking was determined by P-score. A random-effect model was used when heterogeneity was detected; otherwise, a fixed-effect model was used. RESULTS: Six trials comprising 4063 patients formed the comparison network. Compared with everolimus plus exemestane, the combinations of palbociclib or abemaciclib with fulvestrant showed similar efficacies in PFS and no differences in ORR. For the CBR, palbociclib demonstrated improvement, while abemaciclib did not. Incidences of severe adverse events did not significantly differ. A total of 29%, 15.9%, and 4% of patients discontinued everolimus, abemaciclib, and palbociclib, respectively, due to toxicity. CONCLUSION: These results suggest similar efficacies between CDK4/6 inhibition and mTOR blockade; however, CDK4/6 inhibitors were associated with favorable toxicity profiles.

A network meta-analysis of nonsmall-cell lung cancer patients with an activating EGFR mutation: Should osimertinib be the first-line treatment?

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line treatment for nonsmall-cell lung cancer (NSCLC) patients with an activating EGFR mutation. Osimertinib, compared with erlotinib or gefitinib, showed an improvement in progression-free survival (PFS) in a recent trial. The authors compared EGFR TKIs in terms of PFS in a network meta-analysis. METHODS: The PubMed and Embase databases and meeting abstracts were screened for relevant studies between January 2009 and November 2017. A random-effect frequentist network meta-analysis model was conducted to assess PFS. P-score was used to rank treatment effects. RESULTS: Eleven trials with 3145 patients and 5 TKIs (gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) were included. Heterogeneity and inconsistency existed in the network analysis. Gefitinib and erlotinib had similar effects (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.76-1.15). For all patients, the 3 TKIs with the highest probability of benefit were osimertinib, dacomitinib, and afatinib, with P-scores of 91%, 78%, and 46%, respectively. Compared with erlotinib or gefitinib, osimertinib was associated with improvement in men (HR = 0.79, 95% CI, 0.68-0.92), non-Asians (HR = 0.63, 95% CI, 0.40-0.98), smokers (HR = 0.73, 95% CI, 0.56-0.95), and those with a Del19 mutation (HR = 0.69, 95% CI, 0.54-0.90); dacomitinib and afatinib showed no improvement. Toxicity profiles mostly overlapped in all the EGFR TKIs. Toxicity-related death was rare. CONCLUSIONS: Osimertinib was shown to be the best agent to achieve the longest PFS in NSCLC patients with an activating EGFR mutation. However, the benefit of osimertinib might be restricted to certain subgroups.