Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.

Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of ATALANTE-1 was to evaluate its efficacy and safety in these patients. PATIENTS AND METHODS: ATALANTE-1 was a two-step open-label study to evaluate the efficacy and safety of OSE2101 compared to standard-of-care (SoC) chemotherapy (CT). Patients with human leukocyte antigen (HLA)-A2-positive advanced NSCLC without actionable alterations, failing sequential or concurrent CT and ICB were randomized (2 : 1) to OSE2101 or SoC (docetaxel or pemetrexed). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of interim analysis, a decision was taken to prematurely stop the accrual due to coronavirus disease 2019 (COVID-19). Final analysis was carried out in all patients and in the subgroup of patients with ICB secondary resistance defined as failure after ICB monotherapy second line ≥12 weeks. RESULTS: Two hundred and nineteen patients were randomized (139 OSE2101, 80 SoC); 118 had secondary resistance to sequential ICB. Overall, median OS non-significantly favored OSE2101 over SoC {hazard ratio (HR) [95% confidence interval (CI)] 0.86 [0.62-1.19], P = 0.36}. In the secondary resistance subgroup, OSE2101 significantly improved median OS versus SoC [11.1 versus 7.5 months; HR (95% CI) 0.59 (0.38-0.91), P = 0.017], and significantly improved post-progression survival (HR 0.46, P = 0.004), time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration (HR 0.43, P = 0.006) and Quality of Life Questionnaire Core 30 (QLQ-C30) global health status compared to SoC (P = 0.045). Six-month disease control rates and progression-free survival were similar between groups. Grade ≥3 adverse effects occurred in 11.4% of patients with OSE2101 and 35.1% in SoC (P = 0.002). CONCLUSIONS: In HLA-A2-positive patients with advanced NSCLC and secondary resistance to immunotherapy, OSE2101 increased survival with better safety compared to CT. Further evaluation in this population is warranted.

Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small-cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial.

BACKGROUND: The APPLE trial aimed to evaluate the feasibility of longitudinal plasma epidermal growth factor receptor (EGFR) T790M monitoring for the best sequencing strategy of gefitinib and osimertinib. METHODS: APPLE is a randomized, non-comparative, phase II study in patients with common EGFR-mutant, treatment-naive non-small-cell lung cancer including three arms: arm A (osimertinib upfront until RECIST progression, PD), arm B [gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation by cobas EGFR test v2 or RECIST PD], and arm C (gefitinib until RECIST PD), and then switch to osimertinib in both arms. The primary endpoint is the progression-free survival (PFS) rate 'on osimertinib' at 18 months (PFSR-OSI-18) after randomization in arm B (H0: PFSR-OSI-18 of ≤40%). Secondary endpoints include response rate, overall survival (OS), and brain PFS. We report the results of arms B and C. RESULTS: From November 2017 to February 2020, 52 and 51 patients were randomized into arms B and C, respectively. Most patients were females (70%) and had EGFR Del19 (65%); one-third had baseline brain metastases. In arm B, 17% of patients (8/47) switched to osimertinib based on the emergence of ctDNA T790M mutation before RECIST PD, with a median time to molecular PD of 266 days. The study met its primary endpoint of PFSR-OSI-18 of 67.2% (84% confidence interval 56.4% to 75.9%) in arm B versus 53.5% (84% confidence interval 42.3% to 63.5%) in arm C, with a median PFS of 22.0 months versus 20.2 months, respectively. The median OS was not reached in arm B versus 42.8 months in arm C. Median brain PFS in arms B and C was 24.4 and 21.4 months, respectively. CONCLUSIONS: The serial monitoring of ctDNA T790M status in advanced EGFR-mutant non-small-cell lung cancer during treatment with first-generation EGFR inhibitors was feasible, and a molecular progression before RECIST PD led to an earlier switch to osimertinib in 17% of patients with satisfactory PFS and OS outcomes.

Small cell lung cancer: a slightly less orphan disease after immunotherapy.

Small cell lung cancer (SCLC) is an aggressive malignancy accounting for 15% of all diagnosed cases of lung cancer. After >15 years without any clinically relevant therapeutic advances, extensive-disease SCLC has become the second thoracic malignancy for which immune checkpoint inhibitors (ICIs) have shifted the treatment paradigm to improve overall survival. Today, atezolizumab or durvalumab in combination with platinum-etoposide chemotherapy is considered the new standard of care in the first-line setting in SCLC. However, the magnitude of benefit with this immune-chemotherapy strategy in SCLC is more modest than that observed in metastatic non-small-cell lung cancer patients. The immunosuppressive phenotype of SCLC plays an important role in hampering ICI efficacy and may explain the differences in outcomes between these two types of lung cancer. In this review, we provide a summary of recent therapeutic advances in SCLC in light of ICIs, as well as current challenges of this strategy in patients who are elderly, have poor performance status or brain metastases. We also address future perspectives of immunotherapeutic strategies currently in clinical development for these patients.

Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group.

Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well- and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers. Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology.

Osimertinib and other third-generation EGFR TKI in EGFR-mutant NSCLC patients.

Osimertinib was the first third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) to receive FDA and EMA approval for metastatic EGFR-mutant non-small-cell lung cancer (NSCLC) patients that have acquired the EGFR T790M resistance mutation. Clinical trials have demonstrated the efficacy of osimertinib in this patient population and clinical trials of other third-generation EGFR TKI are currently under way. Additional challenges in this patient population, such as the upfront efficacy of osimertinib, validation of T790M in liquid biopsies as a dynamic predictive marker of efficacy, along with combination with immune checkpoint inhibitors are being explored, representing an extraordinary time of development for EGFR-mutant NSCLC.

Are liquid biopsies a surrogate for tissue EGFR testing?

Molecular profiling has changed the treatment landscape in advanced non-small-cell lung cancer. Accurately identifying the tumours that harbour sensitizing EGFR mutations, the most common targetable molecular alteration, as well as those with acquired resistance mutations (e.g. T790M) on treatment is a high clinical priority. The current clinical gold standard is genotyping of tumour specimens. However, the practical utility of this approach is limited by the lack of available tissue and the potential complications associated with biopsies. With the advent of newer sequencing assays, it has become feasible to assess tumour genomics via a blood sample, termed a 'liquid biopsy'. In this review, we summarize the available techniques for liquid biopsies and their applicability for detecting sensitizing and resistance EGFR mutations and how these results may be used for making treatment decisions.

A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups.

BACKGROUND: We report the first study examining the clinical, numerical and biological properties of circulating tumor cells according to molecular subtypes of non-small-cell lung cancer. PATIENTS AND METHODS: 125 patients with treatment-naïve stage IIIb-IV NSCLC were prospectively recruited for CellSearch analysis. Anti-vimentin antibody was included for examination of CTCs to assess their mesenchymal character. Associations of total CTCs and vimentin-positive (vim +) CTCs with clinical characteristics, tumor genotype, and survival were assessed. RESULTS: 51/125 patients (40.8%) were total CTC+ and 26/125 (20.8%) were vim CTC+ at baseline. Multivariate analysis showed patients with ≥5 total CTCs had significantly reduced OS (HR 0.55, 95% CI 0.33-0.92, P = 0.022) but not PFS (HR 0.68, 95% CI 0.42-1.1, P = 0.118) compared to patients with <5 total CTCs. No OS difference was evident between vim+ CTC and vim-negative CTC patients overall (HR 1.24, 95% CI 0.67-2.28, P = 0.494), but after subdivision according to NSCLC driver mutation, we found an increase of vim+ CTCs in the EGFR-mutated subgroup (N = 21/94 patients; mean 1.24 vs 1.22 vim+ CTCs, P = 0.013), a reduction of total CTCs in the ALK-rearranged subgroup (N = 13/90 patients; mean 1.69 vs 5.82 total CTCs, P = 0.029), and a total absence of vim+ CTCs in KRAS-mutated adenocarcinomas (N = 19/78 patients; mean 0 vs 1.4 vim+ CTCs, P = 0.006). CONCLUSIONS: We validate that the baseline presence of ≥5 total CTCs in advanced NSCLC confers a poor prognosis. CTCs from EGFR-mutant NSCLC express epithelial-mesenchymal transition characteristics, not seen in CTCs from patients with KRAS-mutant adenocarcinoma.

Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA.

Background: Approximately 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. Material and methods: ctDNA T790M mutational status was assessed by Inivata InVision™ (eTAm-Seq™) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016. Progressing T790M-positive NSCLC patients received osimertinib (80 mg daily). The objectives were to assess the response rate to osimertinib according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, the progression-free survival (PFS) on osimertinib, and the percentage of T790M positive in ctDNA. Results: The ctDNA T790M mutation was detected in 50% of NSCLC patients. Among assessable patients, osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. All responses were confirmed responses. After median follow up of 8 months, median PFS by RECIST criteria was not achieved (95% CI: 4-NA), with 6- and 12-months PFS of 66.7% and 52%, respectively. Conclusion(s): ctDNA from liquid biopsy can be used as a surrogate marker for T790M in tumour tissue.

Dual MET and ERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC).

BACKGROUND: Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as osimertinib are the last line of targeted treatment of metastatic non-small-cell lung cancer (NSCLC) EGFR-mutant harboring T790M. Different mechanisms of acquired resistance to third-generation EGFR-TKIs have been proposed. It is therefore crucial to identify new and effective strategies to overcome successive acquired mechanisms of resistance. METHODS: For Amplicon-seq analysis, samples from the index patient (primary and metastasis lesions at different timepoints) as well as the patient-derived orthotopic xenograft tumors corresponding to the different treatment arms were used. All samples were formalin-fixed paraffin-embedded, selected and evaluated by a pathologist. For droplet digital PCR, 20 patients diagnosed with NSCLC at baseline or progression to different lines of TKI therapies were selected. Formalin-fixed paraffin-embedded blocks corresponding to either primary tumor or metastasis specimens were used for analysis. For single-cell analysis, orthotopically grown metastases were dissected from the brain of an athymic nu/nu mouse and cryopreserved at -80°C. RESULTS: In a brain metastasis lesion from a NSCLC patient presenting an EGFR T790M mutation, we detected MET gene amplification after prolonged treatment with osimertinib. Importantly, the combination of capmatinib (c-MET inhibitor) and afatinib (ErbB-1/2/4 inhibitor) completely suppressed tumor growth in mice orthotopically injected with cells derived from this brain metastasis. In those mice treated with capmatinib or afatinib as monotherapy, we observed the emergence of KRAS G12C clones. Single-cell gene expression analyses also revealed intratumor heterogeneity, indicating the presence of a KRAS-driven subclone. We also detected low-frequent KRAS G12C alleles in patients treated with various EGFR-TKIs. CONCLUSION: Acquired resistance to subsequent EGFR-TKI treatment lines in EGFR-mutant lung cancer patients may induce genetic plasticity. We assess the biological insights of tumor heterogeneity in an osimertinib-resistant tumor with acquired MET-amplification and propose new treatment strategies in this situation.

Primary Newcastle disease vaccination of broilers: comparison of the antibody seroresponse and adverse vaccinal reaction after eye-nose drop or coarse spray application, and implication of the results for a previously developed coarse dry powder vaccine.

To compare antibody seroresponse and adverse vaccinal reaction induced by Newcastle disease (ND) vaccination after eye-nose drop or coarse spray, groups of SPF broiler hens were vaccinated at day 4 (day of hatch is day 0) and intratracheally inoculated with Escherichia coli at day 11. Body weight gain (BWG) was assessed between day 4 and day 18; colibacillosis lesions and serum antibodies were determined at day 18. Meaningful comparison requires similar vaccine uptake. Vaccine virus loss during spray relative to eye-nose drop, which was assessed by comparing the results of endpoint titrations, was 3 log10. Colibacillosis lesions in birds spray vaccinated with 106.4 EID50/chicken were significantly more severe (P < 0.05), compared to those in birds eye-nose drop vaccinated with 103.4 EID50/chicken, while the seroresponse was slightly but significantly (P < 0.05) stronger. Colibacillosis lesion scores inversely paralleled BWG. It is concluded that: (1) There is room to improve the coarse ND vaccine spray used regarding adverse vaccinal reaction, while maintaining a sufficient immune response. This is also applicable to the coarse ND powder vaccine studied in previous research, which induced similar antibody response and adverse vaccinal reaction as the spray vaccine used here. (2) The vaccine virus dose influences the colibacillosis susceptibility at seven days post vaccination, as the dynamics of the vaccine virus infection is likely dose-dependent. (3) Low vaccine virus doses likely result in heterogeneous vaccine-take followed by vaccine virus spread from vaccine shedding birds to their non-vaccine virus infected flock mates ("rolling vaccinal reaction").

Knowledge of staff members of residential care facilities for individuals with intellectual disability on medication administration via enteral feeding tube.

BACKGROUND: Guidelines for the safe administration of drugs through enteral feeding tube (EFT) are an important tool to minimise the risk of errors. This study aimed to investigate knowledge of these guidelines among staff of residential care facilities (RCF) for people with ID. METHOD: Knowledge was assessed using a 13-item self-administered questionnaire. Questions reflected key aspects of guidelines on medication administration via EFT. All staff members that administer medication through EFT in Belgian RCFs were invited to participate (n = 553). RESULTS: Nine out of 10 RCFs participated, and 356 questionnaires were collected. Almost all participants were women (96%), and most (82%) had a non-nursing educational background. Mean self-perceived knowledge of medication administration via EFT was 6.7 (on a 0-10 scale). On average, 5.7 (SD 1.9) out of 13 questions were answered correctly. A nursing degree and previous education on medication administration via EFT were associated with significantly higher scores. Guideline recommendations regarding rinsing of used medicine cups (90% correct answers) and preparation of hard gelatin capsules (89%) were known best. Those regarding the use of protective equipment when crushing toxic substances (4% correct answers), crushing of sustained release and enteric-coated dosage forms (6%), elevation of the patient's backrest (14%) and flushing of the EFT (15%) were known the least. CONCLUSION: This study identified a substantial lack of knowledge of guidelines for drug administration through EFT among staff of RCFs for people with ID. Our findings call for tailored educational programmes in order to increase knowledge on this subject.

Comparison of Newcastle disease vaccine administered as powder or liquid in relation to the serum antibody response and adverse vaccinal reactions in broilers.

Liquid spray and aerosol mass vaccination of poultry have several drawbacks, such as uncontrolled deposition of vaccine particles in the respiratory tract and vaccine virus inactivation by formation and evaporation of droplets. These may be addressed by using dry powder vaccines with defined particle size distribution targeting the upper (primary vaccination) or the entire respiratory tract (booster vaccination). Therefore, a coarse Newcastle disease (LZ58 strain) powder vaccine was administered to specified pathogen free (SPF) broiler hens to compare the antibody response and adverse vaccinal reactions with those induced by a coarse liquid spray and a fine liquid aerosol. Groups of 40 broilers each housed in isolators were vaccinated at 4 days of age and intratracheally inoculated with Escherichia coli (strain 506) at 11 days of age. Adverse vaccinal reactions were evaluated by measuring body weight gain and mortality between 4 and 11 days of age and between 11 and 18 days of age, and by recording colibacillosis lesions at 18 days of age. The antibody serum response was measured at 18 days of age by the haemagglutination inhibition test. Despite the relative low initial vaccine virus loss and narrow particle size distribution of the powder vaccines in comparison with their liquid counter parts, no significant differences (P > 0.05) regarding adverse vaccinal reactions and antibody response were observed between broilers vaccinated with the powder vaccines or with their liquid counterparts.

Drug administration via enteral feeding tubes in residential care facilities for individuals with intellectual disability: an observational study.

BACKGROUND: The administration of oral medication to patients with an enteral feeding tube (EFT) is challenging. Compliance to guidelines concerning medication administration via EFT has been investigated extensively in the hospital setting. However, studies in residential care facilities (RCFs) for individuals with intellectual disability (ID) are very limited. Therefore, the present study aimed to collect direct observational data on drug administration practices to residents with EFT in multiple RCFs. METHOD: This cross-sectional, observational study was conducted in six Belgian RCFs for individuals with ID. Observations of medication preparation and administration through EFT were carried out in two randomly selected units per participating RCF, on 2 days per unit during all daytime drug rounds, using a direct observation method. Afterwards, the recorded observations were compared with international guidelines on drug preparation and administration through EFT. RESULTS: In total, 862 drug preparations and 268 administrations in 48 residents with EFT were witnessed. Mixing together multiple drugs, not diluting liquid formulations with at least an equal amount of water, not shaking suspensions/emulsions before use, and not selecting the most appropriate dosage form were the most common deviations from medication preparation guideline recommendations. For medication administration, not flushing the EFT with at least 15 mL water was the most common deviation. We also observed high variability in working methods regarding medication preparation and administration via EFT, even between staff members of the same unit. CONCLUSION: This study found that current guidelines concerning medication preparation and administration through EFT are often not followed in Belgian RCFs for individuals with ID. Further research aimed at understanding why current guidelines are not followed seems warranted.

[Effectiveness of pharmaceutical care for patients with COPD: translated review of the recently published PHARMACOP trial]. / Efficacité des soins pharmaceutiques auprès de patients atteints de BPCO: compte-rendu de l'etude PHARMACOP récemment publiée.

BACKGROUND AND AIM: Few well-designed randomized controlled trials (RCT) regarding the impact of community pharmacist interventions on pharmacotherapeutic monitoring of patients with Chronic Obstructive Pulmonary Disease [COPD) have been conducted. We assessed the effectiveness of a pharmaceutical care program for patients with COPD. METHODS: The PHARMACOP-trial was a single-blind 3-month RCT, conducted in 170 community pharmacies in Belgium, enrolling patients prescribed daily COPD medication, aged > or = 50 years, and with a smoking history > or = 10 pack-years. A computer-generated randomization sequence allocated patients to intervention (n = 371), receiving protocol-defined pharmacist care, or control group (n = 363), receiving usual pharmacist care 11:1 ratio, stratified by center). Interventions, focusing on inhalation technique and adherence to maintenance therapy, were carried out at start of the trial and at one month follow-up. Primary outcomes were inhalation technique and medication adherence. Secondary outcomes were exacerbation rate, dyspnea, COPD specific and generic health status and smoking behavior. RESULTS: From December 2010 to April 2011, 734 patients were enrolled. 42 patients (5.7%) were lost to follow-up. At the end of the trial, inhalation score (Mean estimated difference [delta], 13.5%; 95% Confidence Interval [CI], 10.8-16.1; P < .0001] and medication adherence [(delta, 8.51%; 95% CI, 4.63-12.4; P < .0001) were significantly higher in the intervention group compared to the control group. In the intervention group, a significantly lower hospitalization rate was observed (9 vs 35 hospitalizations; Rate Ratio, 0.28; 95% CI, 0.12-0.64; P = .003). No other significant between-group differences were observed. CONCLUSION: The PHARMACOP-trial demonstrates that pragmatic pharmacist care programs improve both inhalation technique and medication adherence in patients with COPD and could reduce hospitalization rates. The protocolled intervention used in this trial was specifically designed for and evaluated in (Belgian) community pharmacies. This may facilitate future implementation in the Belgian context.

Immune checkpoint blockers in solid organ transplant recipients and cancer: the INNOVATED cohort.

BACKGROUND: Patients with solid organ transplant (SOT) and solid tumors are usually excluded from clinical trials testing immune checkpoint blockers (ICB). As transplant rates are increasing, we aimed to evaluate ICB outcomes in this population, with a special focus on lung cancer. METHODS: We conducted a multicenter retrospective cohort study collecting real data of ICB use in patients with SOT and solid tumors. Clinical data and treatment outcomes were assessed by using retrospective medical chart reviews in every participating center. Study endpoints were: overall response rate (ORR), 6-month progression-free survival (PFS), and grade ≥3 immune-related adverse events. RESULTS: From August 2016 to October 2022, 31 patients with SOT (98% kidney) and solid tumors were identified (36.0% lung cancer, 19.4% melanoma, 13.0% genitourinary cancer, 6.5% gastrointestinal cancer). Programmed death-ligand 1 expression was positive in 29% of tumors. Median age was 61 years, 69% were males, and 71% received ICB as first-line treatment. In the whole cohort the ORR was 45.2%, with a 6-month PFS of 56.8%. In the lung cancer cohort, the ORR was 45.5%, with a 6-month PFS of 32.7%, and median overall survival of 4.6 months. The grade 3 immune-related adverse events rate leading to ICB discontinuation was 12.9%. Allograft rejection rate was 25.8%, and risk of rejection was similar regardless of the type of ICB strategy (monotherapy or combination, 28% versus 33%, P = 1.0) or response to ICB treatment. CONCLUSIONS: ICB could be considered a feasible option for SOT recipients with some advanced solid malignancies and no alternative therapeutic options. Due to the risk of allograft rejection, multidisciplinary teams should be involved before ICB therapy.

Optimization of drug delivery systems for intraperitoneal therapy to extend the residence time of the chemotherapeutic agent.

Intraperitoneal (IP) chemotherapy is an effective way of treating peritoneal carcinomatosis of colorectal origin after complete cytoreduction. Although IP therapy has been already performed for many years, no standardized treatment design has been developed in terms of schedule, residence time, drug, or carrier solution. Because of the fast clearance of the conventional intravenous (IV) drug delivery systems used for IP therapy, a lot of research is performed to optimize IP drug delivery and extend the residence time of the cytotoxic agent in the peritoneal cavity. This paper reviews the recent advances made in drug delivery systems for IP chemotherapy, discussing the use of microparticles, nanoparticles, liposomes, micelles, implants, and injectable depots for IP delivery.