Timothée Olivier

• MD
• Hôpitaux Universitaires de Genève

The LUNAR trial investigated the addition of Tumor Treating Fields (TTFs) to “standard therapy” in patients with metastatic lung cancer after at least one line of platinum-based chemotherapy. The “standard therapy” was either an anti-PD(L)1 therapy (immunotherapy) or docetaxel. The addition of TTFs provided a 3.3 months median survival gain. We rai...

The share of immune checkpoint inhibitors (ICIs) used in cancer treatment has rapidly increased in recent years. Although ICIs have the potential to provide a durable survival benefit in a subset of patients, many patients do not respond to these costly and often toxic therapies. Recent retrospective clinical data indicate that the time of day of I...

In 2018, we estimated that eligibility for and response to immune checkpoint inhibitor (ICI) therapies were 44% and 12%, respectively. Since these estimates were published, there have been additional approvals. We sought to provide updated estimates of the percentage of patients with advanced and/or metastatic cancers in the US who are eligible for...

New therapeutic agents in oncology are emerging rapidly, both in terms of the number of approved drugs and the technological and biological innovation of new treatments. Antibody-drug conjugates (ADC) offer a promising cancer therapy by specifically targeting tumor cells. ADC are composed of a monoclonal antibody recognizing the tumor cell via spec...

Clinical endpoints, such as overall survival, directly measure relevant outcomes. Surrogate endpoints, in contrast, are intermediate, stand-in measures of various tumour-related metrics and include tumour growth, tumour shrinkage, blood results, etc. Surrogates may be a time point measurement, that is, tumour shrinkage at some point (eg, response r...

In April 2024, the Food and Drug Administration provided accelerated approval for trastuzumab deruxtecan for adult patients with advanced solid tumors which have positive immunochemical staining for HER2 expression, including sarcomas. There should be ample consideration prior to utilization of trastuzumab deruxtecan for patients with sarcomas, as...

Background Methodological limitations affect a significant number of oncology and haematology trials, raising concerns about the applicability of their results. For example, a suboptimal control arm or limited access to best care upon progression may skew the trial results toward a benefit in the experimental arm. Beyond the fact that such limitati...

Importance In oncology randomized clinical trials, suboptimal access to best available care at recurrence (or relapse) may affect overall survival results. Objective To assess the proportion and the quality of postrecurrence treatment received by patients enrolled in US Food and Drug Administration (FDA) registration trials of systemic therapy in...

e14613 Background: Immune checkpoint inhibitors (ICIs) have notably changed the landscape of systemic treatment of advanced and metastatic cancers in the last decade. We previously estimated the eligibility for and responses to ICIs, but since then, there have been multiple approvals for additional indications. As such, we have updated these estima...

The analysis of randomized clinical trials presents a challenge for clinicians. A set of critical elements can facilitate their interpretation. One must question whether the inclusion and exclusion criteria accurately mirror clinical practice. Does the control arm align with what is currently recognized as best practice? Do patients in the control...

Abtract The SWOG S1801 trial investigated the role of pembrolizumab, an anti-PD1 immune checkpoint inhibitor, in the perioperative setting of stage III or IV melanoma. This phase 2 trial compared two groups: one receiving pembrolizumab both before and after surgery (neoadjuvant-adjuvant), and another receiving it only post-surgery (adjuvant-only),...

Kaplan-Meier analysis hinges on the assumption that patients who are censored– lost to follow-up, or only recently enrolled on the study– are no different, on average, than patients who are followed. As such, censoring these patients– omitting their future information and taking the average of those who were followed– should not dramatically change...

Importance Many economic theories point to regulatory issues and subsidization of research and development costs as the primary factor in the high cancer drug prices in the US. Even so, the association between the median annual cost and novelty of cancer drugs approved in the US remains unclear. Objective To evaluate the association between the me...

Importance The development of therapeutics for patients who are positive for specific human leukocyte antigen (HLA) subtypes evokes the question of whether certain racial and ethnic groups are more or less likely to be eligible for novel products. Objective To determine whether racial and ethnic inequities were present with regard to trial eligibi...

Background The DYNAMIC trial investigated the use of circulating tumor DNA (ctDNA) to guide adjuvant treatment decisions in stage II colon cancer. Despite the DYNAMIC trial’s assertion that a ctDNA-guided approach could minimize the use of adjuvant treatment without compromising recurrence-free survival (RFS), we raised concerns regarding the trial...

Importance: Oral chemotherapy is often dispensed to patients as a 1-month supply, with pill dose and package size predetermined by the drug manufacturer; thus, changing the patient dosage may waste the remaining initial drug supply. The cost of pills wasted due to dose modification and discontinuation is often unreported. Objective: To estimate...

Background: Quality of life (QoL) questionnaires were historically designed in the advanced or metastatic setting. We sought to determine the effects of contemporary treatments on QoL in the adjuvant setting and to determine if the QoL instruments used in these studies provide a valid assessment. Methods: We conducted a systematic identification...

Background Suboptimal treatment upon progression may affect overall survival (OS) results in oncology randomized controlled trials (RCTs). We aim to assess the proportion of trials reporting post-progression treatment. Methods This cross-sectional analysis included two concurrent analyses. The first one examined all published RCTs of anti-cancer d...

PARP inhibitors in ovarian cancer have been a breakthrough therapy of the past decade, driven by positive trial results, and supported by an original pharmacological rationale. However, with mature data, detrimental survival results led to the withdrawals, in 2022, of all approved PARP inhibitors in the most advanced settings’ indication (as monoth...

In patients with glioblastoma, the "DCVax-L" trial reported a survival benefit with the addition of autologous tumor lysate-loaded denditric cell vaccination to the standard-of-care (SoC) in patients with glioblastoma. The trial presented as a phase 3 externally controlled trial is showing an improvement in overall survival (OS) in patients receivi...

Background: Financial difficulties in relation with diagnosis and treatment of patients with cancer affects their quality-of-life (QoL). We aim to characterize how financial toxicity was captured in oncology randomized clinical trials (RCTs), and to estimate how often the study-drug or other expenses were covered by sponsors. Methods: This was a...

Introduction: There has been little consensus for a specific definition of long COVID, though several organizations have created varying ones. We sought to examine the definition of long COVID used in ongoing clinical trials. Methods: We searched 'long COVID' and related terms on both PubMed and clinicaltrials.gov for randomized studies that eit...

This Viewpoint identifies incomplete and missing data in 3 clinical trials to highlight the need for improved data reporting and to propose possible solutions.

The KRAS oncogene is present in up to 25% of solid tumors and for decades had been undruggable. Sotorasib was the first-in-class KRAS inhibitor to reach the US and European market, and its pharmacological inhibition is restricted to the KRAS p.G12C mutation. Sotorasib showed activity (tumor shrinkage) in patients with non-small cell lung cancer har...

Background: The statistical plan of a phase II trial should balance minimizing the premature termination of potentially beneficial therapies (i.e. false negatives) and the further, costly testing of ineffective drugs (i.e. false positives). We sought to examine the methodology, reporting, and bias in the interpretation of outcomes of phase II onco...

Higher diagnostic accuracy, even if desirable, is not automatically associated with better outcomes. If used in settings validated with less sensitive imaging modalities, it is of paramount importance to prospectively ascertain that the higher sensitivity of prostate-specific antigen membrane-based imaging will benefit patients, and will probably n...

Background The utilization of basket trials in oncology has gained popularity because of the drive for precision medicine and the increasing ease of genetically profiling tumors. However, it is unknown if this has translated into patient benefit, either through higher response rates because of precision treatment or because of increasing options fo...

Dostarlimab (Jemperli, GlaxoSmithKline) is an anti-programmed death receptor-1 monoclonal antibody (anti-PD-1) recently tested in a non-randomized, phase II trial (NCT04165772) which included patients with mismatch repair-deficient, locally advanced rectal cancer. Among the first 12 patients treated with dostarlimab, 100% achieved a clinical comple...

Background In the adjuvant setting of cancer treatment, de-escalation strategies have the goal of omitting or minimizing treatment in patients, without compromising outcomes. Historically, eligibility for adjuvant treatment solely relied on the patient’s clinical and tumor’s pathological characteristics. At the turn of the century, based on new bio...

Introduction We sought to characterize oncology basket and umbrella trials that have been implemented, determine how many have been completed, and calculate the responses, by tumor types and drug targets. Methods We conducted a retrospective, cross-sectional review of PubMed, Embase, and clinicaltrials.gov for all oncology basket and umbrella tria...

This cross-sectional study estimates all US Food and Drug Administration anticancer approvals in recent years and evaluates if an association exists between their cost and efficacy.

Objective To examine factors associated with accrual rate in industry sponsored clinical trials supporting US Food and Drug Administration (FDA) cancer drug approvals from 2015 to 2020. Design, setting and participants Retrospective cross-sectional study included 194 pivotal trials supporting cancer drug approvals by the US FDA from 2015 to 2020....

Background Using US population-level data, it has been suggested that novel treatment advances, particularly targeted therapies, have contributed to a sharp fall in NSCLC mortality. Switzerland is a high-income country, with a universal, highly performant health care system, easy access to novel drugs but with different dynamics concerning the smok...

Objectives: Design and reporting of randomized control trials for drug therapies in the adjuvant setting require a nuanced consideration of patient crossover. Adjuvant trials can be susceptible to the misuse of crossover and may distort the interpretation of findings. We sought to investigate and describe crossover and/or postprogression access to...

Aim of the study Different drug modification rules or growth factor support guidance may affect the results in oncology randomised controlled trials. We aimed to estimate the prevalence of unequal rules for dose modification rules or the use of myeloid growth factors in head-to-head registration Food and Drug Administration trials. Methods This cr...

Lu-PSMA was approved in the USA for patients with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer already treated with androgen receptor pathway inhibition and taxane-based chemotherapy on the basis of results from VISION. Three limitations affected the control arm in VISION: choice of the standard of car...

Background Financial costs from cancer treatment are increasingly recognized, but what has historically been underrecognized is the time cost of therapy. We sought to estimate the time burden of anti-cancer drugs approved based on comparisons to best supportive care (BSC), with the assumption that without this drug, a patient could have been treate...

On March 4th 2022, nivolumab received regular US Food and Drug Administration approval, based on the CheckMate 816 trial results, for use “with platinum-doublet chemotherapy for adult patients with resectable NSCLC in the neoadjuvant setting”. This is the first neoadjuvant approval of a checkpoint inhibitor, a unique event in the history of lung ca...

Previous estimates of the likelihood of a drug tested in phase I trials obtaining FDA clearance are out of date. In the intervening years, newer pharmaceuticals have been developed, resulting in new delivery systems and lines of therapies. We sought to explore and update these estimates by comprehensively searching drugs tested in phase I trials an...

In 2021, the US Food and Drug Administration (FDA) approved two drugs targeting exon 20 directly: amivantamab and mobocertinib, under the accelerated approval pathway, for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, whose disease has...

Background Financial costs from cancer treatment are increasingly recognized, but what has historically been underrecognized is the time cost of therapy. We sought to estimate the time burden of anti-cancer drugs approved based on comparisons to best supportive care (BCS), with the assumption that without this drug, a patient could have been treate...

Uveal melanoma is distinct from other melanomas. In the advanced and metastatic stages, little to no improvement have been seen over time. Tebentafusp is a novel mechanism of action bispecific gp100 peptide-HLA-directed CD3 T-cell engager fusion protein (“-fusp”). Tebentafusp was granted full approval on January 25th 2022 in the setting of HLA-A*02...

Background When a new drug comes to the market, the incentive for the sponsoring company is to maximize the treatment duration in order for the patient to reap the full therapeutic benefit of the product and achieve a positive trial result. We sought to enumerate instances when an already-approved oncology drug was used as a comparator for a newer...

Importance: Adjuvant therapies are often approved based on improvements in disease-, progression-, or relapse-free survival (ie, an event). An important estimate in adjuvant therapies is the cost per event averted. Objective: To characterize the costs per event averted of anticancer drugs approved by the US Food and Drug Administration (FDA) bet...

In October 2021, melphalan flufenamide (melflufen) was withdrawn from the US market for the treatment of multiple myeloma. The decision occurred based on results from a phase 3 randomized controlled trial (RCT) which showed numerically inferior overall survival, which previously led the FDA to halt all trials involving this drug. We highlight four...

This cross-sectional study examines the prevalence of restricted choice of treatment in control groups among physicians and investigators conducting oncology randomized clinical trials (RCTs).

The EMERALD trial was an open label phase 3 trial evaluating elacestrant, the first oral selective estrogen receptor degrader (SERD), as compared to “standard of care”, in ER+/HER2- (hormone receptor positive, no HER2 overexpression) advanced or metastatic breast cancer. The EMERALD trial restricted the “standard of care” control arm to limited opt...

Importance Both novel and next-in-class cancer drugs have a role in oncology, but the relative development of each is understudied. Objective To characterize the mechanisms of action of anticancer drugs approved by the US Food and Drug Administration (FDA) between 2009 and 2020, noting how many approvals were based on a new mechanism of action vs...

Modern clinical cancer research increasingly relies on the visual communication of complex response and treatment sequencing data. Graphical representations used in oncology currently fail to provide adequate information on any prior treatment(s) responses, focussing on current treatment effects in isolation. We have developed a new graphical illus...

The ASCENT trial reports impressive results with a median overall survival (OS) increased from 6.7 months to 12.1 months with sacituzumab govitecan over single-agent chemotherapy, in metastatic triple negative breast cancer (TNBC) patients in second and subsequent line of therapy. We described design features in the ASCENT trial casting doubt on th...

Objective: We aimed to systematically characterize reporting missing quality of life (QoL) data in oncology randomized controlled trials (RCTs) and to estimate prevalence of adequate reporting according to existing guidelines. Study Design and Setting: This cross-sectional analysis includes all articles on anti-cancer drugs tested in RCTs in six hi...

The concept of Cancer of Unknown Primary (CUP) has evolved with the advent of medical oncology. CUP can be difficult to diagnose and represents 2 to 5% of new cancers, therefore not exceptionally rare. Within CUPs can be identified a subset of favourable prognosis tumours, however the vast majority of CUP patients belongs to a poor prognosis group....

Background Along with the increasing use of immune checkpoint inhibitors comes a surge in immune-related toxicity. Here, we review the currently available data regarding neurological immune adverse events, and more specifically aseptic meningitis and encephalitis, and present treatment and diagnostic recommendations. Furthermore, we present five ca...

Background To investigate clinical factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in relapsing epithelial ovarian cancer (EOC) patients with BRCA mutations and receiving olaparib as maintenance therapy in real-world. Methods Multicenter (8 hospitals) European retrospective study of relapsing EOC patient...

Objective: To investigate clinical factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in relapsing epithelial ovarian cancer (EOC) patients with BRCA mutations and receiving olaparib as maintenance therapy in daily practice. Methods: Multicenter (8 hospitals) European retrospective study of relapsing EOC...

Immunotherapy by immune checkpoint inhibitors has emerged as an effective treatment for a slight proportion of patients with aggressive tumors. Currently, some molecular determinants, such as the expression of the programmed cell death ligand-1 (PD-L1) or the tumor mutational burden (TMB) have been used in the clinical practice as predictive biomar...

OBJECTIVE: To develop a protocol for immunohisto­ chemistry (IHC) to determine the Schlafen 11 (SLFN11) expression in formalin­fixed, paraffin­embedded (FFPE) high­grade serous ovarian carcinoma (HGSOC) samples. STUDY DESIGN: We validated a reliable SLFN11 an­ tibody (SLFN11­Ab) in IHC choosing between 2 anti­ SLFN11­Abs used for western blot throu...

Purpose: BRCA2 plays a central role in homologous recombination by loading RAD51 on DNA breaks. The objective of this study is to determine whether the location of mutations in the RAD51-binding domain (RAD51-BD; exon 11) of BRCA2 gene impacts the clinical outcome of OC patients. Experimental design: A study cohort of 353 women with OC who under...

Reintroduction of ipilimumab after recovery or hormonal substitution for hypophysitis should be carefully done especially in the presence of minor neurological symptoms or signs (such as tinnitus) which should be considered as red flags for subsequent severe central nervous immune attack.

Bioinformatics is essential in clinical oncology and research. Combining biology, computer science and mathematics, bioinformatics aims to derive useful information from clinical and biological data, often poorly structured, at a large scale. Bioinformatics approaches have reclassified certain cancers based on their molecular and biological present...

The French Sarcoma Group performed this retrospective analysis of the 'RetrospectYon' database with data of patients with recurrent advanced soft tissue sarcoma (STS) treated with trabectedin 1.5mg/m(2) as a 24-h infusion every three weeks. Patients who achieved non-progressive disease after six initial cycles could receive long-term trabectedin tr...

Purpose: The mainstay of first line treatment in metastatic sarcomas is chemotherapy with response rates of ≈25% but the optimal management of further events is debated. We assessed the benefit of local metastatic treatment in metastatic sarcomas. Results: Local control of local treatment strategies (≈85%) is excellent but highly institution-dep...

Background: Choroidal metastases (CM) are the most common malignant intraocular lesion observed in up to 4-12% of necropsy series of patients with solid cancer. The spectrum of presentations varies from prevalent CM in disseminated cancer to isolated CM. CM are responsible for visual deterioration. Depending on the primary cancer, estimated life e...

Aims Recent data suggest that patients with pulmonary metastases from sarcomas might benefit from ablation of their metastases. Some data are available regarding osteosarcomas/angiosarcomas and lung metastases. The purpose of this study was to assess the efficacy of local ablative treatment on the survival of patients with oligometastases (one to f...

Résumé Les métastases sont responsables de la majorité des décès de cancers solides. Le phénomène métastatique, complexe, comporte de multiples étapes où les interactions des cellules entre elles et avec le microenvironnement sont essentielles. Le tropisme d’organe, c’est-à-dire la propension d’un cancer à former des métastases dans tel ou tel orga...