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BackgroundPremature trial discontinuation and non-publication of trial results are still major issues negatively affecting reliable evidence generation.ObjectivesTo investigate trial completion and publication rate of cancer trials conducted within the Swiss Group for Clinical Cancer Research (SAKK).DesignCohort study of clinical trials.SettingCohort of interventional cancer trials conducted in Switzerland with accrual closure between 1986 and 2021 identified from the SAKK trial management system.OutcomesPremature trial discontinuation and publication in peer-reviewed journal.ResultsWe included 261 trials; median number of recruited patients was 150.5 (range 1–8028). Most trials (67.0%) were randomised. Overall, 76 of 261 (29.1%) trials were prematurely closed for accrual. The three main reasons for premature closure were insufficient accrual in 28 trials, followed by stopping for futility in 17 or efficacy in 8 trials. We included 240 trials for the publication status (21 excluded, because 8 still in follow-up, for 10 the primary completion date was less than a year ago and for 3 the manuscript was submitted, but to accepted yet). 216 of 240 (90.0%) were published as a full article, 14 were published in other formats, leading to an overall publication rate of 95.8%. The rate of premature discontinuation declined over time, with 34.2%, 27.8% and 23.5% in trials activated before 2000, between 2000 and 2009, and since 2010, respectively. We observed an increasing publication rate in peer-reviewed journals over time: 79.2% (closed before 2000), 95.7% (closed between 2000 and 2009) and 93.2% (closed after 2010).ConclusionInsufficient patient recruitment is still the major reason for premature trial discontinuation. SAKK has continuously improved its quality management of trial conduct over time leading to increased successful trial completion and publication. However, there is still room for improvement to increase the number of trials reaching their target sample size.

The relapse of follicular lymphoma (FL) within 24 months (POD24) of chemoimmunotherapy has been associated with poor survival. We analyzed a pooled dataset of three randomized trials including FL patients with advanced disease, conducted by the Swiss Group for Clinical Cancer Research (SAKK). Overall, POD24 was observed in 27% of 318 patients, but rate variance among studies suggested that the rituximab schedule might affect POD24 rate. POD24 was associated with lower 10-year overall survival rates than in the reference group (69% vs. 77%; hazard ratio, 3·12; 95% confidence interval, 1·73-5·65). POD24 retains its prognostic validity in patients treated without chemotherapy and may represent a useful end-point for future studies.

Early clinical trials showed promising outcomes with immune-checkpoint inhibitors (ICI) in a subset of patients with relapsed small-cell lung carcinoma (SCLC). The aim of this retrospective analysis was to assess the efficacy and safety of ICI for relapsed SCLC in a real-world patient population. Nine cancer centres in Switzerland contributed data to this cohort. Responses were assessed by the local investigators using standard RECIST v1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were analysed by the Kaplan–Meier method. Associations between potential predictive markers and survival endpoints were probed by Cox proportional hazards. Forty-five patients were included in the analysis. Median age was 63 years, 73% were males and 18% had an ECOG performance status (PS) ≥ 2. ICIs were given as second-line treatment in 60%. Twenty-four patients (53%) received ipilimumab with nivolumab. Twenty-eight patients (62%) had undergone irradiation (RT) prior to or during ICI. Overall response rate (ORR) was 29% and median PFS and OS were 2.3 and 6.5 months, respectively. Median duration of response was 9 months (95% CI 2.8–NA). Five patients maintained their response for > 6 months, all of them receiving combination treatment. There were no new safety signals. This is the first report of “real-world” data on ICI in relapsed SCLC also including patients with poor PS. Promising durable responses were observed. No biological prognostic marker could be identified.

Several functional parameters from baseline (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography have been proposed as promising biomarkers of treatment efficacy in diffuse large B-cell lymphoma (DLBCL). We tested their ability to predict outcome in 2 cohorts of DLBCL patients receiving conventional immunochemotherapy (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone [R-CHOP] regimen), either every 14 (R-CHOP14) or 21 days (R-CHOP21). Baseline PET analysis was performed in 141 patients with DLBCL treated with R-CHOP14 in the prospective SAKK38/07 study (NCT00544219) of the Swiss Group for Clinical Cancer Research (testing set). Reproducibility was examined in a validation set of 113 patients treated with R-CHOP21. In the SAKK38/07 cohort, progression-free survival (PFS) at 5 years was 83% for patients with low metabolic tumor volume (MTV) and 59% for those with high MTV (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.6-7.0; P = .0005), whereas overall survival (OS) was 91% and 64%, respectively (HR, 4.4; 95% CI, 1.9-10; P = .0001). MTV was the most powerful predictor of outcome also in the validation set. Elevated metabolic heterogeneity (MH) significantly predicted poorer outcomes in the subgroups of patients with elevated MTV. A model integrating MTV and MH identified high-risk patients with shorter PFS (testing set: HR, 5.6; 95% CI, 1.8-17; P < .0001; validation set: HR, 5.6; 95% CI, 1.7-18; P = .0002) and shorter OS (testing set: HR, 9.5; 95% CI, 1.7-52; P < .0001; validation set: HR, 7.6; 95% CI, 2.0-28; P = .0003). This finding was confirmed by an unsupervised regression tree analysis indicating that prognostic models based on MTV and MH may allow early identification of refractory patients who might benefit from treatment intensification. This trial was registered at www.clinicaltrials.gov as #NCT00544219.

Myelodysplastic syndromes (MDSs) represent a heterogeneous group of hematological stem cell disorders with an increasing burden on health care systems. Evidence-based MDS guidelines and recommendations (G/Rs) are published but do not necessarily translate into better quality of care if adherence is not maintained in daily clinical practice. Guideline-based indicators (GBIs) are measurable elements for the standardized assessment of quality of care and, thus far, have not been developed for adult MDS patients. To this end, we screened relevant G/Rs published between 1999 and 2018 and aggregated all available information as candidate GBIs into a formalized handbook as the basis for the subsequent consensus rating procedure. An international multidisciplinary expert panel group (EPG) of acknowledged MDS experts (n = 17), health professionals (n = 7), and patient advocates (n = 5) was appointed. The EPG feedback rates for the first and second round were 82% (23 of 28) and 96% (26 of 27), respectively. A final set of 29 GBIs for the 3 domains of diagnosis (n = 14), therapy (n = 8), and provider/infrastructural characteristics (n = 7) achieved the predefined agreement score for selection (>70%). We identified shortcomings in standardization of patient-reported outcomes, toxicity, and geriatric assessments that need to be optimized in the future. Our GBIs represent the first comprehensive consensus on measurable elements addressing best practice performance, outcomes, and structural resources. They can be used as a standardized instrument with the goal of assessing, comparing, and fostering good quality of care within clinical development cycles in the daily care of adult MDS patients.

To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase 3 randomized SAKK 09/10 trial in patients with biochemically recurrent prostate cancer after prostatectomy.Within the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) 09/10 trial testing 64-Gy versus 70-Gy salvage RT, a central collection of treatment plans was performed and thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events version 4.0) and freedom from biochemical progression (FFBP) were investigated.The treatment plans for 344 patients treated between February 2011 and April 2014 depicted important deviations from the EORTC guidelines and the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (eg, prostate bed in 48.8%, rectal wall [RW] in 41%). In addition, variations in clinical target volume (CTV) and planning target volume (PTV) occurred frequently (eg, CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥2 gastrointestinal acute toxicity when the CTV did not overlap the RW versus when the CTV overlapped the RW (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.85; P = .014), and a higher rate of grade ≥2 late genitourinary (GU) toxicity when the CTV overlapped the RW (OR, 2.58; 95% CI, 1.17-5.72; P = .019). A marginally significant lower risk of grade ≥2 late GU toxicity was observed when the prostate bed did not overlap versus did overlap the RW (OR, 0.51; 95% CI, 0.25-1.03; P = .06). In addition, a marginally significant decrease in FFBP was observed in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed (hazard ratio, 1.44; 95% CI, 0.96-2.17; P = .07).Despite a thorough QA program, the central review of a phase 3 trial showed limited adherence to treatment protocol recommendations, which was associated with a higher risk of toxicity by means of acute or late gastrointestinal or GU toxicity and showed a trend toward worse FFBP. Data from this QA review might help to refine future QA programs and prostate bed delineation guidelines.

This phase 1 study evaluated safety, tolerability, and preliminary efficacy of obinutuzumab in combination with venetoclax in patients with previously untreated grade 1-3a follicular lymphoma in need of systemic therapy. Two DLs of venetoclax were evaluated with an expansion cohort at the recommended phase 2 dose. Twenty-five patients were enrolled. The recommended phase 2 dose was venetoclax 800 mg OD continuously for 6 cycles starting on day 2 of cycle 1, with obinutuzumab 1000 mg on days 1, 8, and 15 of cycle 1 and on day 1 of cycles 2 to 6, followed by obinutuzumab maintenance every 2 months for 2 years. Only 1 patient had a DLT consisting of grade 4 thrombocytopenia after the first obinutuzumab infusion. Neutropenia was the most common adverse event of grade ≥3 at least possibly attributed to study treatment. Twenty-four patients were evaluable for response after cycle 6 by computed tomography (CT) and 19 by positron emission tomography/CT (PET/CT): overall and complete response rates were 87.5% (95% CI, 67.6% to 97.3%) and 25% (95% CI, 9.8% to 46.7%) in the CT-evaluated patients and 84.2% (95% CI, 60.4% to 96.6%) and 68.4% (95% CI, 43.4% to 87.4%), respectively, in the PET/CT-evaluated patients. One-year progression-free survival was 77.8% (95% CI, 54.6% to 90.1%) and 79% (95% CI, 47.9% to 92.7%) for CT and PET/CT-evaluable patients, respectively, whereas progression-free survival at 30 months was 73.2% (95% CI, 49.8%, 87.0%) as assessed by CT and 79.0% (95% CI, 47.9%, 92.7%) by PET/CT. Despite the activity observed, our results do not support further development of the combination in this patient population. This trial was registered at www.clinicaltrials.gov as #NCT02877550.

Accurate estimation of the progression risk after first-line therapy represents an unmet clinical need in diffuse large B-cell lymphoma (DLBCL). Baseline (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) parameters, together with genetic analysis of lymphoma cells, could refine the prediction of treatment failure. We evaluated the combined impact of mutation profiling and baseline PET/CT functional parameters on the outcome of DLBCL patients treated with the R-CHOP14 regimen in the SAKK38/07 clinical trial (NCT00544219). The concomitant presence of mutated SOCS1 with wild-type CREBBP and EP300 defined a group of patients with a favorable prognosis and 2-year progression-free survival (PFS) of 100%. Using an unsupervised recursive partitioning approach, we generated a classification-tree algorithm that predicts treatment outcomes. Patients with elevated metabolic tumor volume (MTV) and high metabolic heterogeneity (MH) (15%) had the highest risk of relapse. Patients with low MTV and favorable mutational profile (9%) had the lowest risk, while the remaining patients constituted the intermediate-risk group (76%). The resulting model stratified patients among three groups with 2-year PFS of 100%, 82%, and 42%, respectively (p < 0.001).

Functional parameters from positron emission tomography (PET) seem promising biomarkers in various lymphoma subtypes. This study investigated the prognostic value of PET radiomics in diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP given either every 14 (testing set) or 21 days (validation set). Using the PyRadiomics Python package, 107 radiomics features were extracted from baseline PET scans of 133 patients enrolled in the Swiss Group for Clinical Cancer Research 38/07 prospective clinical trial (SAKK 38/07) [ClinicalTrial.gov identifier: NCT00544219]. The international prognostic indices, the main clinical parameters and standard PET metrics, together with 52 radiomics uncorrelated features (selected using the Spearman correlation test) were included in a least absolute shrinkage and selection operator (LASSO) Cox regression to assess their impact on progression-free (PFS), cause-specific (CSS), and overall survival (OS). A linear combination of the resulting parameters generated a prognostic radiomics score (RS) whose area under the curve (AUC) was calculated by receiver operating characteristic analysis. The RS efficacy was validated in an independent cohort of 107 DLBCL patients. LASSO Cox regression identified four radiomics features predicting PFS in SAKK 38/07. The derived RS showed a significant capability to foresee PFS in both testing (AUC, 0.709; p

Positron emission computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL) enrolled in a prospective clinical trial were reviewed to test the impact of quantitative parameters from interim PET/CT scans on overall (OS) and progression-free (PFS) survival. We centrally reviewed baseline and interim PET/CT scans of 138 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone given every 14 days (R-CHOP14) in the SAKK38/07 trial (ClinicalTrial.gov identifier: NCT00544219). Cutoff values for maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and metabolic heterogeneity (MH) were defined by receiver operating characteristic analysis. Responses were scored using the Deauville scale (DS). Patients with DS 5 at interim PET/CT (defined by uptake >2 times higher than in normal liver) had worse PFS (P = 0.014) and OS (P < 0.0001). A SUVmax reduction (Δ) greater than 66% was associated with longer PFS (P = 0.0027) and OS (P < 0.0001). Elevated SUVmax , MTV, TLG, and MH at interim PET/CT also identified patients with poorer outcome. At multivariable analysis, ΔSUVmax and baseline MTV appeared independent outcome predictors. A prognostic model integrating ΔSUVmax and baseline MTV discriminated three risk groups with significantly (log-rank test for trend, P < 0.0001) different PFS and OS. Moreover, the integration of MH and clinical prognostic indices could further refine the prediction of OS. PET metrics-derived prognostic models perform better than the international indices alone. Integration of baseline and interim PET metrics identified poor-risk DLBCL patients who might benefit from alternative treatments.

Climate change and invasive species threaten biodiversity, yet rigorous monitoring of their impact can be costly. Citizen science is increasingly used as a tool for monitoring exotic species, because citizens are geographically and temporally dispersed, whereas scientists tend to cluster in museums and at universities. Here we report on the establishment of the first exotic ant taxon (Tetramorium immigrans) in Denmark, which was discovered by children participating in The Ant Hunt. The Ant Hunt is a citizen science project for children that we ran in 2017 and 2018, with a pilot study in 2015. T. immigrans was discovered in the Botanical Garden of the Natural History Museum of Denmark in 2015 and confirmed as established in 2018. This finding extends the northern range boundary of T. immigrans by almost 460 km. Using climatic niche modelling, we compared the climatic niche of T. immigrans in Europe with that of T. caespitum based on confirmed observations from 2006 to 2019. T. immigrans and T. caespitum had a 13% niche overlap, with T. immigrans showing stronger occurrence in warmer and drier areas compared to T. caespitum. Mapping the environmental niches onto geographic space identified several, currently uninhabited, areas as climatically suitable for the establishment of T. immigrans. Tetramorium immigrans was sampled almost three times as often in areas with artificial surfaces compared to T. caespitum, suggesting that T. immigrans may not be native to all of Europe and is being accidentally introduced by humans. Overall, citizen scientists collected data on ants closer to cities and harbours than scientists did and had a stronger bias towards areas of human disturbance. This increased sampling effort in areas of likely introduction of exotic species naturally increases the likelihood of discovering species sooner, making citizen science an excellent tool for exotic species monitoring, as long as trained scientists are involved in the identification process.

Background Pomalidomide (POM) with dexamethasone (DEX) is approved in patients (pts) with relapsed and refractory (RRMM) myeloma and achieved a progression free survival (PFS) between 4.0 and 4.6 months in two pivotal phase III trials (MM-003 and MM-010). In addition, POM-DEX is a current standard backbone for triplet combinations in RRMM. However, POM-DEX with registered POM dosing (4mg daily, 21/28 day cycle) has significant toxicity with G3/4 neutropenia (48%), anemia (33%), infections (34%) and thrombocytopenia (22%) in MM-003, and up to 85% G3/4 neutropenia in triplets containing CD38 antibodies. The relationship between dose, efficacy and toxicity of POM is poorly established and POM delivered on a 2mg daily continuous schedule was similarly active compared to the standard schedule, but less toxic. Half life time of POM (7.5h) is significantly longer compared to lenalidomide (3h) with a slow decline of the POM plasma concentration at the terminal phase. Alternate day dosing of POM 4mg may therefore maintain efficacy while mitigating toxicity. This multicenter, open label, non-randomized phase II study investigated the activity and toxicity of POM 4mg given continuously every second day in RRMM pts. Methods Inclusion criteria matched MM-003. Pts with RRMM must have had ≥ 2 prior lines including bortezomib (BORT), lenalidomide (LEN), adequate alkylator treatment, and progressive myeloma on or within 60 days of the last MM treatment. Continuous oral POM 4mg on alternate days 1 to 28 was combined with weekly oral DEX 40mg (pts > 75 years 20mg) until intolerance or progression (PD). Pts received prophylaxis with acyclovir/valacyclovir, cotrimoxazole and ASS. Prophylactic G-CSF was not allowed. Primary endpoint was overall response rate (ORR, minimal response (MR) or better by IMWG criteria). Secondary objectives were overall survival (OS), 12 months OS, PFS and adverse events (AE). Results 34 patients were enrolled (median age 75 yrs, range 52-87) with time from diagnosis of 5.1 yrs (range 1.9-16.8). Prior treatments included LEN (100%), BORT (100%), alkylator (100%), carfilzomib (29%) and daratumumab (27%); 14 (41%) pts had high-risk cytogenetic features. Median treatment duration was 3.6 months. G3/4 AE occurred in less than one quarter of patients: (neutropenia 24%; anemia 18%; infections 18%; thrombocytopenia 12%). Neutropenic fever was not observed. ORR was 29 % (95% confidence interval [CI], 16%-50%; 3 (9%) VGPRs, 6 (8%) PRs and 1 (3%) MR; 15 pts (44%) achieved SD. 9 pts (26%) progressed. Median PFS was 4.2 months (95% CI, 1.9-5.5 months). OS at 12 months was 66.5% (95% CI, 47.6-79.9). Conclusion POM 4mg on an alternate day continuous dosing schedule is an active and well-tolerated option to deliver POM-DEX to RRMM pts and is especially reasonable for patients at increased risk of toxicity. This dosing schedule may have comparable efficacy, improved safety and should be explored in triplet combination.

A well-documented consequence of repeated global ice ages is the negative relationship between latitude and intraspecific genetic diversity. However, little is known about additional effects of such major climatic events on population genetic structure. Here we studied the phylogeographic structure of five lycaenid butterfly species with varied ecological adaptations, sampled across a latitudinal gradient in the Holarctic region. We found a positive correlation between latitude and substitution rate of mitochondrial DNA sequences in all species investigated. We propose that this result is the signal of increased genetic drift and founder effects during post-glacial recolonization of northern populations. Given that phylogenetic branch length is the result of a cumulative process over evolutionary time, we hypothesize that a latitudinal layering of populations has generally been maintained during repeated cycles of glaciation, possibly due to a neutral spatial effect and/or local adaptive advantage. This trans-glacial latitudinal layering could be viewed as a particular case of the more general phenomenon of intraspecific structuring that is created and maintained in a fluctuating environmental gradient.

The role of specialization in diversification can be explored along two geological axes in the butterfly family Lycaenidae. In addition to variation in host-plant specialization normally exhibited by butterflies, the caterpillars of most Lycaenidae have symbioses with ants ranging from no interactions through to obligate and specific associations, increasing niche dimensionality in ant-associated taxa. Based on mitochondrial sequences from 8282 specimens from 967 species and 249 genera, we show that the degree of ecological specialization of lycaenid species is positively correlated with genetic divergence, haplotype diversity and an increase in isolation by distance. Nucleotide substitution rate is higher in carnivorous than phytophagous lycaenids. The effects documented here for both micro- and macroevolutionary processes could result from increased spatial segregation as a consequence of reduced connectivity in specialists, niche-based divergence or a combination of both. They could also provide an explanation for the extraordinary diversity of the Lycaenidae and, more generally, for diversity in groups of organisms with similar multi-dimensional ecological specialization.

Bulletin of Entomological Research, 103 (5), ISSN:0007-4853, ISSN:1475-2670

Social insects such as ants have evolved collective rather than individual immune defence strategies against diseases and parasites at the level of their societies (colonies), known as social immunity. Ants frequently host other arthropods, so-called myrmecophiles, in their nests. Here, we tested the hypothesis that myrmecophily may partly arise from selection for exploiting the ants’ social immunity. We used larvae of the wax moth Galleria mellonella as ‘model myrmecophiles’ (baits) to test this hypothesis. We found significantly reduced abundance of entomopathogens in ant nests compared with the surrounding environment. Specific entomopathogen groups ( Isaria fumosorosea and nematodes) were also found to be significantly less abundant inside than outside ant nests, whereas one entomopathogen ( Beauveria brongniartii ) was significantly more abundant inside nests. We therefore hypothesize that immunological benefits of entering ant nests may provide us a new explanation of why natural selection acts in favour of such a life-history strategy.

Ant microgynes are miniaturized queen forms found together with normal queens (macrogynes) in species occurring across the ant phylogeny. Their role is not yet fully understood: in some cases, they seem to be nonparasitic alternative reproductive morphs, in others incipient social parasites, and thus potential models for studying the evolution of social parasitism. Whether they are regarded as parasitic or not has traditionally been based on genetic differentiation from syntopic macrogynes and/or the queen/worker ratio of their offspring rather than measuring fitness traits. We confirmed previously reported genetic differentiation between microgynes and macrogynes of Myrmica rubra in a population studied for the first time. Further, we measured virulence and infectivity of M. rubra microgynes in a controlled laboratory experiment. Nests headed only by macrogynes (controls), only by microgynes, and naturally and artificially mixed nests were kept under identical conditions. We found reduction in worker numbers of both naturally and artificially mixed macrogyne/microgyne nests compared with controls, and strong reduction but also surprising variation in fitness of nests headed only by microgynes. Microgyne nests produced workers, males and microgynes. Microgynes did not themselves reproduce in artificially mixed nests, but reproduced most in naturally mixed nests that had lost their macrogyne queen. This, together with higher mortality of field-collected macrogyne queens from naturally infested colonies and greater estimated relative age of macrogyne queens in naturally infected nests, suggests that they preferentially exploit older host colonies. We conclude that M. rubra microgynes are intraspecific social parasites specialized on exploiting old host colonies.

The amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) is sensitive to high temperature. Hence, exposing amphibians to high temperature may be a method to clear Bd infection. However, the effect of exposure to elevated temperature has never been tested in larval stages or temperate species. We experimentally exposed tadpoles of the toad Alytes obstetricans to low, medium and high temperatures and found that most, but not all, tadpoles lost the infection when exposed to temperatures higher than 2°C for 5 days. Thus, exposure to elevated temperatures can be used to treat tadpoles against Bd infection.

Key Points Question Is there a role for platinum-based treatment in molecularly selected patients with advanced prostate cancer? Findings In a case series of 508 patients, platinum-based therapy was associated with antitumor activity, especially among patients with known DNA repair gene aberrations. In patients with DNA repair gene aberrations, nearly half had a decrease in prostate-specific antigen levels of at least 50% and experienced soft tissue responses. Meaning In patients with prostate cancer and DNA repair gene aberrations, platinum-based therapy may be considered a treatment option., This case series characterizes the antitumor activity of platinum-based therapies in men with castration-resistant prostate cancer with or without DNA repair gene alterations., Importance DNA repair gene aberrations occur in 20% to 30% of patients with castration-resistant prostate cancer (CRPC), and some of these aberrations have been associated with sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition platinum-based treatments. However, previous trials assessing platinum-based treatments in patients with CRPC have mostly included a biomarker-unselected population; therefore, efficacy in these patients is unknown. Objective To characterize the antitumor activity of platinum-based therapies in men with CRPC with or without DNA repair gene alterations. Design, Setting, and Participants In this case series, data from 508 patients with CRPC treated with platinum-based therapy were collected from 25 academic centers from 12 countries worldwide. Patients were grouped by status of DNA repair gene aberrations (ie, cohort 1, present; cohort 2, not detected; and cohort 3, not tested). Data were collected from January 1986 to December 2018. Data analysis was performed in 2019, with data closure in April 2019. Exposure Treatment with platinum-based compounds either as monotherapy or combination therapy. Main Outcomes and Measures The primary end points were as follows: (1) antitumor activity of platinum-based therapy, defined as a decrease in prostate-specific antigen (PSA) level of at least 50% and/or radiological soft tissue response in patients with measurable disease and (2) the association of response with the presence or absence of DNA repair gene aberrations. Results A total of 508 men with a median (range) age of 61 (27-88) years were included in this analysis. DNA repair gene aberrations were present in 80 patients (14.7%; cohort 1), absent in 98 (19.3%; cohort 2), and not tested in 330 (65.0%; cohort 3). Of 408 patients who received platinum-based combination therapy, 338 patients (82.8%) received docetaxel, paclitaxel, or etoposide, and 70 (17.2%) received platinum-based combination treatment with another partner. A PSA level decrease of at least 50% was seen in 33 patients (47.1%) in cohort 1 and 26 (36.1%) in cohort 2 (P = .20). In evaluable patients, soft tissue responses were documented in 28 of 58 patients (48.3%) in cohort 1 and 21 of 67 (31.3%) in cohort 2 (P = .07). In the subgroup of 44 patients with BRCA2 gene alterations, PSA level decreases of at least 50% were documented in 23 patients (63.9%) and soft tissue responses in 17 of 34 patients (50.0%) with evaluable disease. In cohort 3, PSA level decreases of at least 50% and soft tissue responses were documented in 81 of 284 patients (28.5%) and 38 of 185 patients (20.5%) with evaluable disease, respectively. Conclusions and Relevance In this study, platinum-based treatment was associated with relevant antitumor activity in a biomarker-positive population of patients with advanced prostate cancer with DNA repair gene aberrations. The findings of this study suggest that platinum-based treatment may be considered an option for these patients.