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BMC Cancer Jul 2021Although various clinical trials and real-life studies have tried to explore the value of nab-paclitaxel mono-chemotherapy for metastatic breast cancer (MBC), the safety... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although various clinical trials and real-life studies have tried to explore the value of nab-paclitaxel mono-chemotherapy for metastatic breast cancer (MBC), the safety and efficacy of nab-paclitaxel remain unclear which need to be systematically evaluated.
METHODS
Electronic searches for prospective clinical trials evaluating nab-paclitaxel monotherapy for MBC were performed. Requisite data were extracted, integrated and analysed from the included studies according to the different study designs using systematic review and meta-analysis. Meta-regression and subgroup analysis were further performed to explore the potential risk factors affecting each individual outcome of interest following nab-paclitaxel monotherapy.
RESULTS
Twenty-two studies with 3287 MBC patients were included. A total of 1685 MBC patients received nab-paclitaxel as first-line therapy, 640 patients as further-line therapy, and 962 patients as mixed-line therapy. A total of 1966 MBC patients (60.40%) received nab-paclitaxel weekly, 1190 patients (36.56%) received nab-paclitaxel triweekly and 99 patients (3.04%) received nab-paclitaxel biweekly. The overall incidence rates of all-grade neutropenia, leukopenia, peripheral sensory neuropathy, and fatigue were 52% (95% CI, 38-66%, I = 98.97%), 58% (95% CI, 43-73%, I = 97.72%), 58% (95% CI, 48-68%, I = 97.17%), and 49% (95% CI, 41-56%, I = 94.39%), respectively. The overall response rate (ORR) was 40% (95% CI, 35-45%, I = 98.97%), and the clinical benefit rate (CBR) was 66% (95% CI, 59-73%, I = 98.97%) following nab-paclitaxel monotherapy. The median progression-free survival (PFS) was 7.64 months (95% CI, 6.89-8.40 months, I = 92.3%), and the median overall survival (OS) was 24.51 months (95% CI, 21.25-27.78 months, I = 92.7%). Treatment line, human epidermal growth factor receptor-2(Her-2)-negative status and dosage were found to be sources of heterogeneity among the included studies. According to the meta-regression and subgroup analysis, grade 3/4 neutropenia occurred less frequently in Her-2-negative patients than in the entire population (P = 0.046). Patients who received first-line nab-paclitaxel monotherapy showed a higher ORR (P = 0.006) and longer PFS (P = 0.045). Efficacy outcomes were not affected by the administration schedule. However, within the same schedule, patients appeared to have a superior ORR (P = 0.044) and longer PFS (P = 0.03) with an increasing dosage of nab-paclitaxel administered.
CONCLUSIONS
The benefits brought by nab-paclitaxel mono-chemotherapy in the treatment of MBC are considerable while the harm is generally manageable. Further study and validation are needed to figure out the roles which the dosage, schedule and other factors play actually in nab-paclitaxel chemotherapy.
Topics: Albumins; Breast Neoplasms; Female; Humans; Neoplasm Metastasis; Paclitaxel; Risk Factors; Treatment Outcome
PubMed: 34275458
DOI: 10.1186/s12885-021-08441-z -
Cureus May 2021Background Peripheral neuropathy (PN), especially peripheral sensory neuropathy (PSN), is significant toxicity of taxanes, the most used class of microtubule inhibitors...
Relative Risk of Peripheral Neuropathy With Ado-Trastuzumab Emtansine (T-DM1) Compared to Taxane-Based Regimens in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Cancers: A Systematic Review and Meta-Analysis.
Background Peripheral neuropathy (PN), especially peripheral sensory neuropathy (PSN), is significant toxicity of taxanes, the most used class of microtubule inhibitors for human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. Ado-trastuzumab emtansine (T-DM1) is a HER2-targeted antibody-drug conjugate, consisting of trastuzumab and a microtubule inhibitor DM1, which has been approved for HER2-positive breast cancer. T-DM1 has also been found to cause significant PN, including PSN. Methods We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials using T-DM1 in the experimental arm and a taxane-based regimen in the control arm to determine the relative risk of PN and PSN associated with T-DM1 as compared to taxanes. A total of 1,857 patients were included in the analysis. The Cochran-Mantel-Haenszel method and the random-effects model were used to calculate the pooled risk ratio (RR) with a 95% confidence interval (CI) for all-grade and grade ≥3 PN and PSN. Results The relative risks of all-grade PN and all-grade PSN were lower with T-DM1 compared to taxanes. The pooled RR of all-grade PN was 0.59, 95% CI: 0.39-0.89, P = 0.01, and the pooled RR of all-grade PSN was 0.58, 95% CI: 0.46-0.74, P < 0.0001. Conclusions Our meta-analysis demonstrated that T-DM1 is associated with a relatively lower risk of all-grade PN and PSN than the taxane-based regimens for HER2-positive cancers. It could be an area of consideration in selecting therapy for HER2-positive breast cancer patients at high risk of developing or having pre-existing PN and PSN.
PubMed: 34194883
DOI: 10.7759/cureus.15282 -
Gland Surgery May 2021The benefits of neoadjuvant chemotherapy (NCT) in pancreatic cancer (PC) have been realized and gradually accepted. FOLFIRINOX and gemcitabine and nab-paclitaxel (GA)...
Head-to-head comparison between FOLFIRINOX and gemcitabine plus nab-paclitaxel in the neoadjuvant chemotherapy of localized pancreatic cancer: a systematic review and meta-analysis.
BACKGROUND
The benefits of neoadjuvant chemotherapy (NCT) in pancreatic cancer (PC) have been realized and gradually accepted. FOLFIRINOX and gemcitabine and nab-paclitaxel (GA) are the two most widely used regimens for PC NCT.
METHODS
The literature was systematically reviewed by searching MEDLINE, EMBASE, Web of Science and the Cochrane Library for studies published until September 2020.
RESULTS
Eight studies were eligible for the meta-analysis. Compared to GA, neoadjuvant FOLFIRINOX significantly prolonged overall survival [hazard ratio (HR) =0.65, 95% confidence interval (95% CI): 0.55-0.77; P<0.001]. FOLFIRINOX provided better survival benefits in the first three years after surgery; however, the 4- and 5-year survival probabilities of the two strategies were similar based on a conservative estimation in the random effect model. The perioperative parameters analysed included perineural invasion (PNI), lymphovascular invasion (LVSI), R0 status, postoperative complications and resection rate. The PNI rate was marginally elevated in the GA group compared with the FOLFIRINOX cohort [79.8% 70.5%, odds ratio (OR) =0.70, 95% CI: 0.47-1.06, P=0.09], which may account for the potential survival benefits of FOLFIRINOX.
CONCLUSIONS
The results of our meta-analysis suggest that FOLFIRINOX is non-inferior to GA in patients who are FOLFIRINOCX capable.
PubMed: 34164301
DOI: 10.21037/gs-21-16 -
Arab Journal of Urology Mar 2021: To systematically review the use of drug-eluting stents (DES) and drug-coated balloons (DCB) in urology. (Review)
Review
OBJECTIVE
: To systematically review the use of drug-eluting stents (DES) and drug-coated balloons (DCB) in urology.
MATERIALS AND METHODS
The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Scopus, Web of science and Cochrane Library online databases were searched in February 2019. Experimental and clinical studies, which included the placement of a DES or dilatation with DCB for investigating their potential use in the urinary tract for the management of ureteric or urethral pathologies, were included. The primary endpoint was to evaluate the current use of DES and DCB in urology.
RESULTS
A total of 29 articles were included in the systematic review. A total of 10 studies tested DES or DCB containing anti-proliferative agents (paclitaxel, zotarolimus, sirolimus, halofugione). Antibiotic agent-containing DES were tested in nine studies (triclosan, quinolones, teicoplanin, nitrofurantoin, silver sulfadiazine). A total of eight studies investigated the release of anti-inflammatory agents by DES (ketorolac, indomethacin, EW-7197). Another group studied heparin-eluting stents.
CONCLUSION
Despite the inconclusive outcomes of the three randomised controlled trials, drug-coated/eluting devices constitute a promising field in urology for the prevention of complications associated with conventional stents including pain and encrustation. Pre-clinical and studies have shown their ability to mitigate inflammation, inhibit re-stenosis and improve pain as indicated by declined use of anti-inflammatory drugs.: DES: drug-eluting stents; DCB: drug-coated balloons; DCS: drug-coated stents; HF: halofungione; MCP-1: monocyte chemoattractant protein 1; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PTCA: percutaneous transluminal coronary angioplasty; RANTES: regulated on activation, normal T-cell expressed and secreted; RCT: randomised controlled trial; USSQ, Ureteric Stent Symptoms Questionaire.
PubMed: 34104496
DOI: 10.1080/2090598X.2021.1885948 -
Journal of Gastrointestinal Oncology Apr 2021Epithelial ovarian cancer (EOC) causes 60% of ovarian cancer cases and is the fourth most common cause of death from cancer in women. The standard of care for EOC... (Review)
Review
Epithelial ovarian cancer (EOC) causes 60% of ovarian cancer cases and is the fourth most common cause of death from cancer in women. The standard of care for EOC includes a combination of surgery followed by intravenous chemotherapy. Intraperitoneal (IP) chemotherapy (CT) has been introduced into the therapeutic algorithm of EOC with positive results. To explore existing results regarding intraperitoneal chemotherapy a systematic review of the literature and an analysis of our own institutional prospective database of patients treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) for EOC at different stages were conducted. The focused report concerning our personal experience with advanced EOC treated with cytoreductive surgery and HIPEC produced the following results: In 57 patients cisplatin + paclitaxel as HIPEC was the only significant factor improving overall survival (OS) at multivariate analysis (OR 6.54, 95% CI: 1.24-34.47, P=0.027). Patients treated with HIPEC cisplatin + paclitaxel showed a median OS of 46 months (SD 6.4, 95% CI: 33.4-58.6), while patients treated with other HIPEC regimens showed a median OS of 12 months (SD 3.1, 95% CI: 6.0-18.0). The 2y-OS was 72% and 3y-OS was 68% for cisplatin + paclitaxel as HIPEC, while the 2y- and 3y-OS was 0% for other HIPEC regimens. Patients treated with HIPEC cisplatin + paclitaxel showed a median disease-free survival (DFS) of 13 months (SD 1.6, 95% CI: 9.9-16.1), while patients treated with other HIPEC regimens showed a median DFS of 8 months (SD 3.1, 95% CI: 1.9-14.1). In conclusion, HIPEC cisplatin + paclitaxel in ovarian cancer showed positive results that may be considered semi-definitive according to the level of evidence and should be considered a starting point for further investigations. At present HIPEC cisplatin + paclitaxel should be proposed to patients with advanced ovarian cancer as standard treatment at almost all stages of disease. Platinum + taxane-based intraperitoneal regimens demonstrated superior results compared to other regimens.
PubMed: 33968435
DOI: 10.21037/jgo-2020-06 -
The Cochrane Database of Systematic... Mar 2021Epidermal growth factor receptor (EGFR) mutation positive (M+) non-small cell lung cancer (NSCLC) is an important subtype of lung cancer comprising 10% to 15% of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epidermal growth factor receptor (EGFR) mutation positive (M+) non-small cell lung cancer (NSCLC) is an important subtype of lung cancer comprising 10% to 15% of non-squamous tumours. This subtype is more common in women than men, is less associated with smoking, but occurs at a younger age than sporadic tumours.
OBJECTIVES
To assess the clinical effectiveness of single-agent or combination EGFR therapies used in the first-line treatment of people with locally advanced or metastatic EGFR M+ NSCLC compared with other cytotoxic chemotherapy (CTX) agents used alone or in combination, or best supportive care (BSC). The primary outcomes were overall survival and progression-free survival. Secondary outcomes included response rate, symptom palliation, toxicity, and health-related quality of life.
SEARCH METHODS
We conducted electronic searches of the Cochrane Register of Controlled Trials (CENTRAL) (2020, Issue 7), MEDLINE (1946 to 27th July 2020), Embase (1980 to 27th July 2020), and ISI Web of Science (1899 to 27th July 2020). We also searched the conference abstracts of the American Society for Clinical Oncology and the European Society for Medical Oncology (July 2020); Evidence Review Group submissions to the National Institute for Health and Care Excellence; and the reference lists of retrieved articles.
SELECTION CRITERIA
Parallel-group randomised controlled trials comparing EGFR-targeted agents (alone or in combination with cytotoxic agents or BSC) with cytotoxic chemotherapy (single or doublet) or BSC in chemotherapy-naive patients with locally advanced or metastatic (stage IIIB or IV) EGFR M+ NSCLC unsuitable for treatment with curative intent.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified articles, extracted data, and carried out the 'Risk of bias' assessment. We conducted meta-analyses using a fixed-effect model unless there was substantial heterogeneity, in which case we also performed a random-effects analysis as a sensitivity analysis.
MAIN RESULTS
Twenty-two trials met the inclusion criteria. Ten of these exclusively recruited people with EGFR M+ NSCLC; the remainder recruited a mixed population and reported results for people with EGFR M+ NSCLC as subgroup analyses. The number of participants with EGFR M+ tumours totalled 3023, of whom approximately 2563 were of Asian origin. Overall survival (OS) data showed inconsistent results between the included trials that compared EGFR-targeted treatments against cytotoxic chemotherapy or placebo. Erlotinib was used in eight trials, gefitinib in nine trials, afatinib in two trials, cetuximab in two trials, and icotinib in one trial. The findings of FASTACT 2 suggested a clinical benefit for OS for participants treated with erlotinib plus cytotoxic chemotherapy when compared to cytotoxic chemotherapy alone, as did the Han 2017 trial for gefitinib plus cytotoxic chemotherapy, but both results were based on a small number of participants (n = 97 and 122, respectively). For progression-free survival (PFS), a pooled analysis of four trials showed evidence of clinical benefit for erlotinib compared with cytotoxic chemotherapy (hazard ratio (HR) 0.31; 95% confidence interval (CI) 0.25 to 0.39 ; 583 participants ; high-certainty evidence). A pooled analysis of two trials of gefitinib versus paclitaxel plus carboplatin showed evidence of clinical benefit for PFS for gefitinib (HR 0.39; 95% CI 0.32 to 0.48 ; 491 participants high-certainty evidence), and a pooled analysis of two trials of gefitinib versus pemetrexed plus carboplatin with pemetrexed maintenance also showed evidence of clinical benefit for PFS for gefitinib (HR 0.59; 95% CI 0.46 to 0.74, 371 participants ; moderate-certainty evidence). Afatinib showed evidence of clinical benefit for PFS when compared with chemotherapy in a pooled analysis of two trials (HR 0.42; 95% CI 0.34 to 0.53, 709 participants high-certainty evidence). All but one small trial showed a corresponding improvement in response rate with tyrosine-kinase inhibitor (TKI) compared to chemotherapy. Commonly reported grade 3/4 adverse events associated with afatinib, erlotinib, gefitinib and icotinib monotherapy were rash and diarrhoea. Myelosuppression was consistently worse in the chemotherapy arms; fatigue and anorexia were also associated with some chemotherapies. Seven trials reported on health-related quality of life and symptom improvement using different methodologies. For each of erlotinib, gefitinib, and afatinib, two trials showed improvement in one or more indices for the TKI compared to chemotherapy. The quality of evidence was high for the comparisons of erlotinib and gefitinib with cytotoxic chemotherapy and for the comparison of afatinib with cytotoxic chemotherapy.
AUTHORS' CONCLUSIONS
Erlotinib, gefitinib, afatinib and icotinib are all active agents in EGFR M+ NSCLC patients, and demonstrate an increased tumour response rate and prolonged PFS compared to cytotoxic chemotherapy. We found a beneficial effect of the TKI compared to cytotoxic chemotherapy in adverse effect and health-related quality of life. We found limited evidence for increased OS for the TKI when compared with standard chemotherapy, but the majority of the included trials allowed participants to switch treatments on disease progression, which will have a confounding effect on any OS analysis. Single agent-TKI remains the standard of care and the benefit of combining a TKI and chemotherapy remains uncertain as the evidence is based on small patient numbers. Cytotoxic chemotherapy is less effective in EGFR M+ NSCLC than erlotinib, gefitinib, afatinib or icotinib and is associated with greater toxicity. There are no data supporting the use of monoclonal antibody therapy. Icotinib is not available outside China.
Topics: Afatinib; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bias; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cetuximab; Crown Ethers; ErbB Receptors; Erlotinib Hydrochloride; Female; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Paclitaxel; Pemetrexed; Progression-Free Survival; Protein Kinase Inhibitors; Quality of Life; Quinazolines; Randomized Controlled Trials as Topic
PubMed: 33734432
DOI: 10.1002/14651858.CD010383.pub3 -
Frontiers in Oncology 2021Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) for non-metastatic locoregionally advanced nasopharyngeal carcinoma (NPC) has gained...
BACKGROUND
Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) for non-metastatic locoregionally advanced nasopharyngeal carcinoma (NPC) has gained considerable attention. However, the most efficacious IC regimens remain investigational. We aimed to compare the survival benefits of all available IC regimens followed by CCRT in this network meta-analysis.
METHODS
All randomized-controlled trials of CCRT with or without IC in non-metastatic locoregionally advanced NPC were included, with an overall nine trials of 2,705 patients counted in the analysis. CCRT alone was the reference category. Eight IC regimens followed by CCRT were analyzed: docetaxel + cisplatin (DC), gemcitabine + carboplatin + paclitaxel (GCP), gemcitabine + cisplatin (GP), mitomycin + epirubicin + cisplatin + fluorouracil + leucovorin (MEPFL), cisplatin + epirubicin + paclitaxel (PET), cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX) and cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX). Fixed-effects frequentist network meta-analysis models was applied and P-score was used to rank the treatments.
RESULTS
DC, GP, and PX were the top three IC regimens with the highest probability of benefit on overall survival (OS). Their corresponding hazard ratios (HRs) (95% CIs) compared with CCRT alone were of 0.24 (0.08-0.73), 0.43 (0.24-0.77), and 0.54 (0.27-1.09) and the respective P-scores were 94%, 82%, and 68%. The first three IC regimens showing significantly improved progression-free survival (PFS) were PX, followed by GP and DC with respective HRs of 0.46 (0.24-0.88), 0.51 (0.34-0.77), and 0.49 (0.20-1.20), and P-scores of 82%, 78%, and 74%. Among the studies in the intensity-modulated radiation therapy (IMRT) era, GP and PX were the best performed IC regimens, whilst DC performed the best among non-IMRT studies. Doublet and gemcitabine-based IC regimens had better survival benefits compared to triplet and taxane-based IC regimens, respectively.
CONCLUSIONS
Given its consistent superiority in both OS and PFS, DC, GP, and PX ranked among the three most efficacious IC regimens in both the overall and subgroup analysis of IMRT or non-IMRT studies. Exploratory analyses suggested that doublet and gemcitabine-based IC regimens showed better survival performance.
PubMed: 33718193
DOI: 10.3389/fonc.2021.626145 -
BMC Cancer Feb 2021To compare the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and solvent-based taxanes (sb-taxanes) as neoadjuvant therapy in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To compare the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and solvent-based taxanes (sb-taxanes) as neoadjuvant therapy in the treatment of breast cancer.
METHODS
We systematically searched the PubMed, Embase, and Cochrane Central Register databases. Randomized controlled trials (RCTs) and cohort studies, published in English, about the comparison between nab-paclitaxel and sb-taxanes as neoadjuvant therapy in patients with breast cancer were searched up to September 2019.
RESULTS
The primary outcome was the proportion of patients with pathological complete response (pCR, defined as ypT0 ypN0 or ypT0/is ypN0). Other main outcomes included long-term survival and adverse events (AEs). Seven studies (five RCTs and two cohorts) and 2949 patients were included. Neoadjuvant nab-paclitaxel improved pCR compared with sb-taxanes (ypT0 ypN0: OR = 1.52, 95%CI: 1.27-1.83, P < 0.001; ypT0/is ypN0: OR = 1.40, 95%CI: 1.17-1.68, P < 0.001). The benefits of nab-paclitaxel on pCR were persistent in HER2-negative, hormone receptor (HR)-positive breast cancer (OR = 1.53, 95%CI: 1.07-2.19, P = 0.020), triple-negative breast cancer (weekly/every 2 weeks regimen; OR = 2.95, 95%CI: 1.54-5.67, P < 0.001), and tumors with Ki-67 > 20% (OR = 1.63, 95%CI: 1.26-2.12, P < 0.001). Patients treated with nab-paclitaxel had better event-free survival (EFS; HR = 0.69, 95%CI: 0.57-0.85, P < 0.001) than with sb-taxanes. There were no differences in most of grade > 3 AEs between nab-paclitaxel and sb-taxanes (all P > 0.05), besides of any grade hypersensitivity (OR = 0.29, 95%CI: 0.11-0.72, P = 0.008), any grade (OR = 2.10, 95%CI: 1.37-3.23, P = 0.001) and grade > 3 (OR = 4.01, 95%CI: 2.51-6.41, P < 0.001) neuropathy.
CONCLUSION
Nab-paclitaxel is effective for the treatment of non-metastatic breast cancer in the neoadjuvant setting. Nab-paclitaxel could improve pCR rate and EFS compared with sb-taxanes and with reasonable toxicities.
Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Humans; Paclitaxel; Prognosis; Randomized Controlled Trials as Topic; Solvents; Taxoids
PubMed: 33541289
DOI: 10.1186/s12885-021-07831-7 -
Surgical Case Reports Feb 2021Patients with advanced-stage breast cancer often demonstrate pancreatic metastases. However, pancreatic metastases resection from breast cancer has been rarely...
BACKGROUND
Patients with advanced-stage breast cancer often demonstrate pancreatic metastases. However, pancreatic metastases resection from breast cancer has been rarely performed, with only 20 cases having been reported to date.
CASE PRESENTATION
A 49-year-old woman presented to our hospital in September 2003 with complaints of uncontrollable oozing from her left breast tumor. Computed tomography revealed a left breast tumor approximately 9.3 cm in diameter as well as heterogeneously enhanced solid mass lesions with necrotic foci in the pancreatic tail and body, up to 6.2 cm, which were radiologically diagnosed as pancreatic metastases from breast cancer. An emergent left simple mastectomy was performed to control bleeding. After epirubicin and cyclophosphamide hydrate treatment failed to improve her condition, the pancreatic metastases responded to weekly paclitaxel treatment, but eventually regrew. The patient underwent distal pancreatectomy with splenectomy, left adrenalectomy, partial stomach resection, and paraaortic lymph nodes excision in December 2004 after no other metastasis was confirmed. Furthermore, she received radiation therapy for left parasternal lymph node metastasis 6 months later. The patient recovered well. Consequently, she has no evidence of disease > 15 years after pancreatectomy.
CONCLUSIONS
This is the first reported case of pancreatectomy for pancreatic metastases from breast cancer, which was simultaneously diagnosed. Patients with no metastasis other than resectable pancreatic metastases and breast cancer and who possess some sensitivity for chemotherapy may benefit from pancreatectomy.
PubMed: 33534098
DOI: 10.1186/s40792-021-01124-8 -
Therapeutic Advances in Medical Oncology 2020Multiple therapies including immune-checkpoint inhibitors are emerging as effective treatment for patients with recurrent or metastatic head and neck squamous cell...
Immune-checkpoint inhibitor plus chemotherapy conventional chemotherapy for treatment of recurrent or metastatic head and neck squamous cell carcinoma: a systematic review and network meta-analysis.
BACKGROUND
Multiple therapies including immune-checkpoint inhibitors are emerging as effective treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSSC). However, the optimal first-line and second-line treatments remains controversial.
METHODS
We systematically searched databases and conducted a systematic review of phase II/III randomized controlled trials (RCTs) that compared two or more treatments for R/M HNSSC. Progression-free survival (PFS), overall survival (OS) and adverse events (AEs) ⩾3 with hazard ratios (HRs) were extracted and synthesized based on a frequentist network meta-analysis.
RESULTS
Twenty-six trials involving 8908 patients were included. Of first-line treatments, pembrolizumab plus cisplatin plus 5-fluorouracil is associated with significantly improved OS (P-score = 0.91) and TPEx ranked first for prolonging PFS (0.91). EXTREME plus docetaxel (0.18) ranked lowest for AEs ⩾3. Of second-line treatments, nivolumab was the highest-ranked treatment for prolonging OS (0.95), while buparlisib plus paclitaxel was the highest-ranked treatment for PFS (0.94). Subgroup analyses suggested that nivolumab was significantly associated with improvement of OS in patients with high PD-L1 expression (HR 0.55, 0.43-0.70), whereas its OS benefit is similar with conventional chemotherapy for those with low PD-L1 expression. Buparlisib plus paclitaxel showed the best OS benefit in subgroups of patients with HPV-negative status, and with oral cavity or larynx as primary tumor sites.
CONCLUSIONS
Pembrolizumab plus cisplatin plus 5-fluorouracil is likely to be the best first-line treatment when OS is a priority. Otherwise, TPEx should be the optimal first-line option due to its superior PFS prolongation efficacy, best safety profile, and similar OS benefit with pembrolizumab plus cisplatin plus 5-fluorouracil. Nivolumab appears to be the best second-line option with best OS prolongation efficacy and outstanding safety profile in the overall population. Future RCTs with meticulous grouping of patients and detailed reporting are urgently needed for individualized treatment.
PubMed: 33488783
DOI: 10.1177/1758835920983717