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OBJECTIVE: The purpose of this study was to review the effectiveness of immune checkpoint inhibitors (ICIs) in the first-line treatment of advanced non-small cell lung carcinoma with wild-type epidermal grow factor receptor (EGFR) or anaplastic lymphoma kinase. MATERIALS AND METHODS: After a standard literature search, we identified all randomized studies published on this issue. Our first inclusion criterion was the use of pembrolizumab, nivolumab, atezolizumab or durvalumab in the treatment arm versus chemotherapy in the control arm. The second criterion was the availability of information on overall survival at 2 years. The restricted mean survival time (RMST) was used to analyze the survival curves and rank the treatments. RESULTS: From the eligible studies, we selected 5 randomized trials that met our inclusion criteria. These trials studied a total of 11 cohorts of patients in whom the treatment arm received ICI as monotherapy (n=3) or in combination with either chemotherapy (n=2) or other monoclonal antibodies (n=1). All the control groups (n=5) received chemotherapy. Pembrolizumab (alone or in combination) showed improvement in overall survival compared with controls, but with borderline statistical significance. Nivolumab, atezolizumab and durvalumab failed to demonstrate any survival advantage. Overall, the RMSTs provided more conservative results than those previously reported using the hazard ratio. In comparing the values of RMST across treatments, pembrolizumab combined with chemotherapy ranked first. CONCLUSIONS: Our results summarized the efficacy of these treatments and showed that only pembrolizumab can have a role as the firstline treatment of NSCLC. These findings are at variance with those previously reported using the hazard ratio as the outcome measure. [ABSTRACT FROM AUTHOR]

Background: The implantation of cardiac implantable electronic devices (CIEDs) carries a known risk of infection. Two devices (TYRX and TauroPace) have been proposed to reduce this risk., Methods: The aim of our study was to compare the effectiveness of TauroPace and TYRX. Real-world comparative studies were included. Data analysis was based on reconstruction of individual patient data from Kaplan-Meier curves using an artificial intelligence algorithm. The endpoint was CIED infection or systemic infection. Statistical tests included heterogeneity assessment, superiority testing, and non-inferiority testing. The primary outcome measure was the hazard ratio (HR) with confidence interval (CI)., Results: Our literature search identified two real-world studies suitable for our analysis. Follow-up was 12 months for TauroPace (654 patients) and 60 months for TYRX (872 patients), with a total of 2,083 controls. There was no heterogeneity among controls. Compared to the pooled control group, patients treated with TYRX or TauroPace had fewer CIED infections (HR, 0.3892; 95% CI, 0.2042-0.7419; P=0.00414; HR, 0.3313; 95% CI, 0.1005-1.0925; P=0.06958, respectively). When testing for non-inferiority of TauroPace vs. TYRX, the comparison yielded a HR of 0.8494 (in favor of TYRX) with a 90% CI of 0.27-2.63; this CI of TauroPace did not meet the non-inferiority criterion set at HR>0.75 (i.e., relative difference ≤25%)., Conclusions: Both treatments had some important drawbacks. Regarding TYRX, more selective use in higher-risk patients should be advocated to improve its cost-effectiveness, but robust evidence is still lacking. Regarding TauroPace, our analysis testing for a non-inferiority margin of ≤25% did not meet this demonstration., Competing Interests: None., (AJCD Copyright © 2024.)

Three techniques of catheter ablation (CA; radiofrequency, cryoballoon, and pulsed-field ablation) are available to treat patients with paroxysmal atrial fibrillation (PAF) who do not adequately respond to pharmacological treatments. Our study was aimed at comparing these techniques based on the data of randomized studies because these are considered the best sources of efficacy data. After selecting pertinent trials, our analysis studied the time-to-event data published for these three techniques. An artificial intelligence method was used that reconstructs individual patient data from the Kaplan-Meier curves. The endpoint was an arrhythmia recurrence. A preliminary heterogeneity analysis was performed. Then, our main analysis was based on individual patient data reconstructed from Kaplan-Meier graphs. The hazard ratio (HR) was its main parameter. Three randomized trials were included. Our heterogeneity analysis confirmed an acceptable level of between-trial heterogeneity that allowed us to pool the curves from the different trials; however, cryoballoon ablation with a two-minute duration fared worse than the other techniques. Then, our main analysis estimated the following values of HR: pulsed-field ablation versus radiofrequency ablation, 0.549 (95%CI, 0.413-0.730; p<0.001); pulsed-field ablation versus cryoballoon ablation, 0.478 (95%CI, 0.364-0.633); radiofrequency ablation versus cryoballoon ablation, HR=0.871 (95%CI, 0.585-1.295; p=0.506). In conclusion, radiofrequency ablation and cryoballoon ablation showed similar effectiveness (except for the two-minute cryoballoon ablation, which fared worse). Our results showing the superiority of pulsed-field ablation versus thermal ablation must be interpreted with caution because the patients given pulsed-field ablation were limited, and their follow-up was shorter than that of patients receiving thermal ablation., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rivano et al.)

Introduction: In patients with paroxysmal atrial fibrillation, pulsed-field ablation has been developed as an alternative to thermal ablation. Three devices are currently available: Farawave by Boston, PulseSelect by Medtronic, and Varipulse by Johnson. In the present report, we studied the outcomes at 12 months of these three devices using indirect comparisons., Methods: A standard PubMed search was conducted that identified all studies evaluating these devices in patients with paroxysmal atrial fibrillation. The endpoint was freedom from arrhythmia recurrence. Kaplan-Meier curves were subjected to the IPDfromKM method that generated reconstructed patients. Standard time-to-event statistical testss (including heterogeneity assessment) were performed., Results: Our analysis included 9 studies (8 single-arm and 1 randomized trial based on Farawave for a total of 1916 patients). A significant heterogeneity was found across the trials using Farawave because the outcomes found in the single-arm trials were better than those found in the randomized trial. Farawave (according exclusively to the results of the randomized trial), PulseSelect, and Varipulse showed a similar time-course of their respective outcomes with no significant difference. The single-arm trials using Farawave showed better outcomes than the randomized trial using Farawave and the pivotal trials using PulseSelect and Varipulse., Discussion: Our study provided an updated overview of all the studies that have so far used pulsed-fileld ablation in patients with paroxysmal atrial fibrillation., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The reconstruction of individual patient data from published Kaplan-Meier survival curves is a new technique (often denoted as the IPDfromKM method) for studying efficacy in cases where multiple trials are available, and the endpoint is long-term mortality. In patients with tricuspid regurgitation, both valve repair and valve replacement have been proposed to improve prognosis; 6 controlled clinical trials (CTs) have been conducted to compare the two therapeutic options mentioned above. The objective of our analysis was to study these six trials through the application of the IPDfromKM method., Methods: In the present report, we applied the IPDfromKM method to carry out a pooled analysis of these 6 CTs to investigate the effectiveness of valve repair vs valve replacement and to assess the between-study heterogeneity from this clinical material. After reconstructing individual patient data from these 6 trials, patients treated with valve repair were pooled together and their Kaplan-Meier curve was generated. Likewise, patients treated with valve replacement were pooled together and their Kaplan-Meier curve was generated. Finally, these two curves were compared by standard survival statistics. The hazard ratio (HR) was determined; death from any cause was the endpoint., Results: These 6 CTs included a total of 552 patients; in each of these CTs, the patient group treated with valve repair was compared with another group treated with valve replacement. Our statistical results showed a significantly better survival for valve repair compared with valve replacement (HR, 0.6098; 95% confidence intervals (CI), 0.445 to 0.835; p = 0.002). Heterogeneity was found to be significant in the 6 patient arms undergoing replacement, but not in those undergoing valve repair. In valve replacement, the classification of patients in class III or IV of New York Heart Association (NYHA) was the main negative prognostic factor., Conclusions: Our analysis confirmed the methodological advantages of the IPDfromKM method in the indirect comparative analysis of multiple trials. These advantages include appropriate analysis of censored patients, original assessment of heterogeneity, and graphical presentation of the results, wherein individual patients retain an important role., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Although MitraClip has been studied in numerous trials, its evidence in the long term is based on a few original studies. We used an original technique of evidence synthesis to review long-term comparative trials evaluating MitraClip. We searched the PubMed database to select long-term comparative trials of MitraClip. The endpoint was all-cause mortality (minimum follow-up, one year). Included trials were analyzed using the IPDfromKM (reconstruct Individual Patient Data from published Kaplan-Meier survival curves) method to reconstruct individual patient data from Kaplan-Meier curves. Standard survival statistics were used to interpret these long-term efficacy data. The survival benefit per patient was estimated from the restricted mean survival time (RMST). Six comparative studies of MitraClip were included; 973 patients were treated with MitraClip (six arms), 717 with medical therapy (five arms), and 80 with surgical repair or replacement (one arm). In our main analysis, the outcomes observed in patients treated with MitraClip were significantly better than those of medical therapy (hazard ratio for all-cause mortality, 0.5276; 95% confidence interval, 0.4412 to 0.6309; p < 0.001); the number of patients treated with surgery was too small to make reliable comparisons. Median survival was 30.4 months for medical therapy versus not reached for the other two groups. RMST was 43.931 and 33.756 months for MitraClip and controls, respectively, yielding a gain per patient of 10.17 months (95% confidence interval, 7.47 to 12.88). In our simplified cost-effectiveness evaluation, a gain of approximately 10 months per patient compared favorably with the device cost. Our analysis provided an original interpretation of the long-term evidence available on MitraClip., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Messori et al.)

In Philadelphia chromosome-positive B-cell (Ph+) acute lymphoblastic leukemia (LLA), growing evidence has accumulated regarding the efficacy of low-intensity and chemo-free regimens. Our objective was to analyze all recent trials evaluating these treatments and to compare them in terms of efficacy. We applied the Shiny method, an artificial intelligence technique, to analyze Kaplan-Meier curves and reconstruct patient-level data. Reconstructed patient data were then evaluated through standard survival statistics and subjected to indirect head-to-head treatment comparisons. The endpoint was progression-free survival (PFS). Based on 432 reconstructed patients, eight trials were analyzed. The survival data from these trials were pooled into three types of treatments: (i) treatments based on tyrosine kinase inhibitors (TKIs) combined with reduced-intensity chemotherapy (denoted as TKICHE); (ii) TKIs associated with steroids with no chemotherapy (TKISTE); (iii) chemotherapy-free combinations of blinatumomab plus TKIs (TKIBLI). According to the Shiny method, the three PFS curves were reported in a single Kaplan-Meier graph and subjected to survival statistics. In terms of PFS, TKIBLI ranked first, TKICHE second, and TKISTE third; the differences between these three regimens were statistically significant. This multi-treatment Kaplan-Meier graph, generated through the Shiny method, summarized the current evidence on these treatments in both qualitative and quantitative terms.

Objectives: The aim of the budget impact analysis (BIA) was to determine the economic impact of introducing risdiplam in the treatment of type 3 spinal muscular atrophy (SMA) patients in a rare diseases reference centre on a 3-year time horizon, as compared with nusinersen., Methods: Public databases were used to estimate the target population. Two market scenarios were assessed over a 3-year time horizon: with nusinersen and with the introduction of risdiplam. Drug acquisition and administration costs were considered. BIA is calculated as the difference between scenarios with nusinersen - scenario with risdiplam., Results: The introduction of risdiplam would generate a 3-year saving of €3411.50. There could be a saving in the administration of risdiplam in the treatment of patients under the age of 2 with a weight of 5 kg (€26 382.08)., Conclusion: The BIA shows the overlapping costs of these therapies, although the oral administration of risdiplam could be a decisive factor for the therapeutical switch from nusinersen., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pembrolizumab (PEM) and tislelizumab (TIS), in combination with chemotherapy, have demonstrated significant clinical benefits in first-line treatment of advanced non-small cell lung cancer (NSCLC). However, no head-to-head clinical trial has yet compared these two treatments., Methods: We conducted a literature search of randomized trials, in which TIS plus chemotherapy or PEM plus chemotherapy were studied for the first-line treatment of NSCLC. Randomized design and the endpoint of progression-free survival (PFS) were the inclusion criteria for our analysis. Adjusted indirect comparison between TIS and PEM was performed by application of the IPDfromKM-Shiny method. This method is based on the reconstruction of individual patient data from Kaplan-Meier curves. Outcomes in terms of PFS were expressed as hazard ratio (HR) with 95% and 90% confidence interval (CI)., Results: Data were extracted from five randomized trials involving nearly 2,000 participants. In comparing PEM plus chemotherapy (n=748) or TIS plus chemotherapy (n=462) vs. chemotherapy alone (n=782), the Shiny method found a significant advantage in terms of PFS (HR =0.5856, 95% CI: 0.4986-0.6876 for TIS; HR =0.5573, 95% CI: 0.4969-0.6251 for PEM), thus confirming the results of the original trials. The indirect comparison of PEM plus chemotherapy vs. TIS plus chemotherapy showed a substantial equivalence between these two regimens (HR =0.952; 95% CI: 0.775-1.168; 90% CI: 0.801-1.130) suggesting an acceptable degree of equivalence according to regulatory criteria. Medians were 8.89 months for PEM combination, 7.97 months for TIS combination, and 5.69 for the controls., Conclusions: The PFS of TIS combined with chemotherapy was similar to that of PEM combined with chemotherapy. Based on the HR with 90% CI, these two agents met an equivalence criterion for PEM vs. TIS ranging from -19.9% to +13.0%.

Value-based price is estimated quite frequently for medicines, but its application to medical devices is scarce. While some reports have been published in which this parameter has occasionally been determined for devices, no large-scale application has yet been reported. Our objective was to pursue a systematic analysis of the literature published on value-based prices of medical devices. Pertinent papers were selected upon the criterion that the value-based price was reported for the device examined. The real prices of the devices were compared with their values of value-based price and the ratios between real price versus value-based price were calculated. A total of 239 economic articles focused on high-technology medical devices were selected from a standard PubMed search. Among these, the proportion of analyses unsuitable for value-based price estimation was high (191/239; 80%), whereas adequate clinical and economic information for estimating this parameter was available in 48 cases (20%). Standard equations of cost-effectiveness were applied. The value-based price was determined according to a willingness-to-pay threshold of 60,000 € per quality-adjusted life year. Real prices of devices were compared with the corresponding estimates of value-based prices. From each analysis, we extracted also the value of incremental cost-effectiveness ratio (ICER). Our final dataset included 47 analyses because one was published twice. There were five analyses in which the ICER could be estimated for the treatment, but not for the device. In the dataset of 42 analyses with complete information, 36 out of 42 devices (86%) were found to have an ICER lower than the pre-specified threshold (favorable ICER). Three ICERs were borderline. A separate analysis was conducted on the other three devices that showed an ICER substantially greater than the threshold (unfavorable ICER). Regarding value-based prices, the values of real price were appreciably lower than the corresponding value-based price in 36 cases (86%). For three devices, the real price was substantially higher than the value-based price. In the remaining three cases, real prices and value-based prices were very similar. To our knowledge, this is the first experience in which a systematic analysis of the literature has been focused on the application of value-based pricing in the field of high-technology devices. Our results are encouraging and suggest a wider application of cost-effectiveness in this field., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hyeraci et al.)

In the area of evidence-based medicine, the IPDfromKM-Shiny method is an innovative method of survival analysis, midway between artificial intelligence and advanced statistics. Its main characteristic is that an original software investigates the Kaplan-Meier graphs of trials so that individual-patient data are reconstructed. These reconstructed patients represent a new form of original clinical material. The typical objective of investigations based on this method is to analyze the available evidence, especially in oncology, to perform indirect comparisons, and determine the place in therapy of individual agents. This review examined the most recent applications of the IPDfromKM-Shiny method, in which a new web-based software-published in 2021-was used. Reported here are 14 analyses, mostly focused on oncological treatments. Indirect comparisons were based on overall survival or progression free survival. Each of these analyses provided original information to compare treatments with one another and select the most appropriate depending on patient characteristics. These analyses can also be useful to assess equivalence from a regulatory viewpoint. All investigations stressed the importance of heterogeneity to better interpret the evidence generated by IPDfromKM-Shiny investigations. In conclusion, these investigations showed that the reconstruction of individual patient data through this online tool is a promising new method for analyzing trials based on survival endpoints. This new approach deserves further investigation, particularly in the area of indirect comparisons.

Background: When COVID-19 pandemic started, Italian hospital pharmacists faced multiple challenges and change their work practices., Objectives: The aim of this study was to describe the impact of COVID-19 emergency on pharmaceutical care provided by pharmacists during the first wave of the pandemic. Issues related to pharmacist's involvement in the pandemic management were: changes in activities, support received by authorities and pharmacists' own perceived role in the Health System., Methods: A cross-sectional study based on a web survey was conducted between May and June 2020 collecting information from pharmacists, members of Italian Society of Clinical Pharmacy and Therapeutics. 113 (11.4%) completed the questionnaire. The cohort was divided in 2 arms: pharmacists who worked in severely COVID-19 affected areas (High Spread Regions) and those employed in less affected areas (Low Spread Regions)., Results: The changes in pharmacy work settings reflected the increase of logistics area and non-sterile clinical galenic, and reduction of clinical tasks. The most demanding challenge was referred to shortages of medical devices and drugs, 61/113 pharmacists reported difficulty in obtaining products compliant to quality standards. National Institutions and Regional Governments provided a greater perceived support. More than 50% of participants felt that their role did not change if compared to other health professionals., Conclusions: Despite some limitations related to their clinical activity, pharmacists played a crucial role in supplying personal protective equipment, medical devices and medications to improve health outcomes during this emergency. The results may guide pharmacists in future actions to improve the management of the pandemic.

In recent years, new treatments have been studied for relapsed-refractory multiple myeloma (RRMM), including two CAR-T products and a variety of non-CAR-T agents. Since direct comparisons between these innovative treatments are not available, indirect comparisons can be of interest. Reconstruction of individual patient data from Kaplan-Meier graphs (e.g., according to the Shiny method) has been the subject of numerous reports that have fully validated their performance. In the present systematic review, we evaluated six treatments proposed for RRMM, including two CAR-T products (ciltacabtagene autoleucel and idecabtagene vicleucel) and four treatments not based on a CAR-T (melflufen plus dexamethasone, isatuximab plus dexamethasone, selinexor, and belantamab). The endpoint was overall survival (OS). Our results showed statistically significant differences in OS across these treatments. In particular, ciltacabtagene autoleucel showed better OS than idecabtagene vicleucel. As regards non-CAR-T treatments, the ranking in OS was headed by isatuximab plus dexamethasone, followed by belantamab, selinexor, and melflufen plus dexamethasone. In conclusion, while the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons have offered some original clues to interpret the results of OS published in these studies.

Background and objectives Glofitamab, tafasitamab, loncastuximab tesirine, polatuzumab, and selinexor have been proposed for the treatment of relapsed-refractory diffuse large B-cell lymphoma (DLBCL). We studied the pattern of overall survival (OS) for these five agents. Methods We reconstructed patient-level data from the Kaplan-Meier OS graphs published in five pivotal trials. For this purpose, we used an artificial intelligence technique (the Shiny method). Reconstructed survival curves were subjected to standard statistics to perform cross-trial indirect comparisons; medians and hazard ratios (HRs) with 95% confidence interval (CI) were estimated for each treatment. Results Using glofitamab (a bispecific antibody) as a common comparator, our analysis of OS yielded the following results: a) tafasitamab plus lenalidomide, HR: 0.514 (95% CI: 0.341 to 0.776; P=0.0015); b) polatuzumab vedotin, HR: 0.822 (95% CI: 0.509 to 1.327); c) selinexor, HR: 1.170 (95% CI: 0.852 to 1.603); and d) loncastuximab tesirine, HR: 1.120 (95% CI: 0.868 to 1.659). Medians were estimated as follows: a) tafasitamab plus lenalidomide, 26.5 months (95% CI: 18.9 to NA); b) polatuzumab vedotin, 12.5 months (95% CI: 9.03 to NA); c) glofitamab, 11.7 months (95% CI: 7.96 to 18.0); d) loncastuximab tesirine, 10.2 months (95% CI: 6.97 to 11.6); and e) selinexor, 10.1 months (95% CI: 6.72 to 14.2). Conclusions These comparative results represent an original finding generated by the Shiny method. Although these comparisons are indirect, our analysis offers a useful synthesis of the outcomes of these treatments. According to these results, glofitamab, despite its improved mechanism of action, does not seem to confer any OS advantage compared with the other four treatments., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Messori et al.)

Introduction: The clinical choice among recently approved cancer drugs is burdened by the absence of direct comparisons in terms of efficacy across these new agents. In this article we present the IPDfromKM method, an artificial intelligence (AI) application that aims to facilitate the analyses on efficacy based on secondary data., Methods: Seven therapeutic areas were selected in which at least three new agents were recently approved. Kaplan-Meier curves of related clinical trials were digitized. Then, the IPDfromKM method was employed to reconstruct patient-level survival data. This information allowed us to compare selected agents in each therapeutic area and to rank them in terms of efficacy., Results: We identified the most effective treatment in each of the seven selected therapeutic areas. In two cases, immunotherapies, sharing similar mechanisms of actions, were compared highlighting the most effective one. In the remaining cases, our comparison included also the standard of care, which proved to be superior to new agents in patients with osteosarcoma., Discussion: When randomized clinical trials are not available, indirect comparisons can be a valuable source of information. The experience described herein recommends the use of a new method endowed by two important advantages: remarkable speed of analysis and free access to computational tools. In assessing the place in therapy for newly developed agents, this approach can further promote the application of evidence-based principles.

Introduction: In recent years, new treatments have been approved for nonmetastatic castration-resistant prostate cancer (M0CRPC). Because direct comparisons between these treatments are not available to guide treatment decisions, indirect comparisons can be of interest., Methods: Our analysis evaluated second-generation hormone treatments proposed for M0CRPC. We searched multiple databases for articles published between 2010 and 2022. Phase-III clinical trials that studied these agents in M0CRPC patients were eligible. Among these, we included trials reporting overall survival (OS) through Kaplan-Meier curves. We performed the reconstruction of individual patient data from Kaplan-Meier graphs, according to the Shiny method, to indirectly compare the efficacy of the different agents. Indirect comparisons included testing for equivalence according to FDA criteria. Confidence intervals (CI) were 95% in all analyses except equivalence testing, where 90%CIs were used., Results: Three studies met these inclusion criteria. Apalutamide (hazard ratio [HR]: 0.75, 95% confidence interval [CI] 0.64-0.88), darolutamide (HR 0.70, 95%CI 0.58-0.84), and enzalutamide (HR 0.77, 95%CI 0.65-0.90) were all significantly more effective than the placebo. Our results showed no difference in OS between any of these three agents, and in testing for equivalence, our estimates of HR met the 0.75-1.33 level., Conclusions: While the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons based on mature OS demonstrated similar efficacy and substantial equivalence among these three second-generation androgen receptor inhibitors., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective This paper presents a preliminary experience based on the "one-to-many" approach of the Shiny method. Numerous (or "many") treatments for advanced or metastatic urothelial carcinoma have recently been reviewed. More recently, "one" potentially innovative treatment has been made available. Our analysis was aimed at assessing the benefits of the new treatment in comparison with the alternatives developed previously. Materials and methods The Shiny method was employed to reconstruct patient-level survival data. This information allowed us to compare the Kaplan-Meier (KM) curves of five treatments previously available (i.e., pembrolizumab, nivolumab, atezolizumab, vinflunine, and standard chemotherapy) with the potentially innovative agent represented by enfortumab vedotin. Overall survival was evaluated for each agent. Statistical tests to assess head-to-head indirect comparisons were performed through standard survival analysis. The hazard ratio (HR) was the main parameter. Results In ranking the efficacy across these agents, enfortumab vedotin was first, followed by immune checkpoint inhibitors (ICIs). Standard chemotherapy and vinflunine were the least effective. The remarkable survival results of enfortumab were, to some extent, influenced by the slightly better prognosis of the population enrolled in the enfortumab trial in comparison with patients enrolled in the three ICI trials. Conclusions The experience described herein shows that, when a potential innovative treatment (enfortumab vedotin) is developed in an already investigated area (metastatic urothelial cancer), the Shiny method can be applied according to the "one-to-many" approach. This allows us to quickly assess the place in therapy of the new treatment (the "one") and to evaluate whether the new treatment determines a relevant incremental benefit in comparison with previous treatments (the "many")., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Messori et al.)

Background: In PD-L1-negative patients with advanced non-small-cell lung cancer (NSCLC), conclusive evidence in support of specific treatments remains lacking. Objectives: The efficacy of first-line chemoimmunotherapy versus chemotherapy alone was compared. Methods: Eligible randomized studies that included patients with advanced NSCLC irrespective of PD-L1 status who were treated with chemoimmunotherapy as the first line were identified. Kaplan-Meier curves were extracted and analyzed using restricted mean survival time (RMST). Patient-level data were reconstructed from progression-free survival (PFS) graphs. A Bayesian network meta-analysis (NETMA) was carried out. Results: In five trials selected, chemoimmunotherapy regimens, compared with chemotherapy alone, resulted in an improvement in PFS without statistical significance. In the NETMA, chemoimmunotherapy was found to slightly improve PFS. Conclusion: This analysis showed that the incremental benefit of chemoimmunotherapy versus chemotherapy is limited.