FDA 2025 Cancer Drug Approvals: targeted therapy dominates.

This article provides an overview of FDA's regulatory processes for drug development and approval, and the estimated costs associated with the development of a drug, and also examines the issues and challenges facing the FDA in the near future. A literature search was performed using MEDLINE to summarize the current FDA drug approval processes and future directions. MEDLINE was further utilized to search for all cost analysis studies performed to evaluate the pharmaceutical industry R&D productivity and drug development cost estimates. While the drug approval process remains at high risk and spans over multiple years, the FDA drug review and approval process has improved, with the median approval time for new molecular drugs been reduced from 19 months to 10 months. The overall cost to development of a drug remains quite high and has been estimated to range from $868M to $1,241M USD. Several new laws have been enacted, including the FDA Safety and Innovation Act (FDASIA) of 2013, which is designed to improve the drug approval process and enhance access to new medicines. The FDA's improved processes for drug approval and post-market surveillance have achieved the goal of providing patients with timely access to effective drugs while minimizing the risk of drug-related harm. The FDA drug approval process is not without controversy, as a number of well-known gastroenterology drugs have been withdrawn from the US market over the past few years. With the approval of the new FDASIA law, the FDA will continue to improve their processes and, working together with the ACG through the FDA-Related Matters Committee, continue to develop safe and effective drugs for our patients.

INTRODUCTION: Historical migration patterns, systemic inequities, and biological factors such as genetic polymorphisms and microbiome diversity all contribute to varied treatment responses among different racial and ethnic groups. Dr. Yedjou’s “Health and Racial Disparity in Breast Cancer” reported that while there is only a 2.6% difference in the incidence rate of breast cancer between White and Black women, Black women are 42% more likely to die from breast cancer than White women. While there may be other factors that play a role in these statistics, current trial designs often fail to account for the differences present amongst race and ethnic groups, leading to regulatory approvals based on non-generalizable data. Generalizability refers to the ability to infer the average treatment effect from a sample to the entire target population. In order to further evaluate the generalizability of breast cancer drugs from the past decade (2015 to 2025), we reviewed the FDA’s “Oncology (Cancer) /Hematologic Malignancies Approval Notifications” webpage. METHODS: Between February 3, 2015 and January 27, 2025, we identified 33 breast cancer drug approvals and used the DRIVE calculator to evaluate the generalizability of drug approval for target populations for which they will be used. Each study was examined for the inclusion of demographic data and reporting of the racial/ethnic composition of its participants. Following this review, a DRIVE score, ranging from 0 to 5, was assigned to each study, with a designation of “0x” or “0*” given if the racial/ethnic data was not reported or was reported separately, respectively. We have previously defined a minimum DRIVE score of 3 as the benchmark for clinical excellence and relevance based on racial representation. Demographic information was recorded as it was available at the time of abstract submission, based on the NCI clinical trial results section. RESULTS: A total of 9 breast cancer clinical trials met the criteria for clinical trial excellence, revealing an overwhelming lack of generalizability within these FDA drug approvals. Over this ten year period, 24 clinical trials failed to meet the minimum requirements for clinical trial excellence. The full score breakdown is as follows: 3 received a score of 0x, 2 received a score of 0, 5 received a score of 0*, 13 received a score of 1, 1 received a score of 2, 8 received a score of 3, 1 received a score of 4, and 0 received a score of 5. CONCLUSION: Our findings reveal that 9 out of 33 of the clinical trials associated with FDA approvals met the minimum criteria for clinical trial excellence. Although all the breast cancer drugs evaluated have received FDA approval, 72.5% do not accurately represent the intended patient populations. This lack of representation exacerbates disparities, particularly among minoritized populations, and leaves critical gaps in understanding potential adverse reactions or side effects. The aim of this analysis is to emphasize the need to minimize therapeutic misconceptions, the assumption that approved drugs with promising clinical trial data have demonstrated effectiveness across all patient populations. A clear understanding of the DRIVE Score Ranking and its purpose can assist clinicians and patients identify which drugs are supported by generalizable and transportable data, ultimately guiding more inclusive and equitable clinical research practices. For these reasons, we advocate for the exclusive use of trials meeting the minimum standards for “clinical trial excellence” as the basis of FDA approvals ensuring equitable benefits for all patients. Citation Format: M. N. Birhiray, S. Ranger, R. E. Birhiray. The generalizability and transportability of FDA drug approvals in breast cancer from 2010 - 2025 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD1-03.

11030 Background: Drug regulators operate on their own timelines to assess the safety and efficacy of new drugs and/or extensions to existing indications, such that there are delays between regulators. During such a gap, patients in the “early” domain have access to the approved drug, while those in the “late” domain do not, outside of compassionate use. Our study aimed to quantify the “opportunity lost” for new therapies approved by FDA and EMA, assuming patients in the late domain receive standard-of-care (SOC) therapy – which is presumably inferior to the new drug – during the gap. Methods: Anticancer drugs approved by both FDA and EMA were identified through the HemOnc knowledgebase. Inclusion criteria included: 1) drugs approved in both domains based on the same randomized clinical trial (RCTs) for the same indication; 2) a primary time-to-event endpoint; and 3) a quantitated median time-to-event for the primary endpoint. For each included trial, the approval gap between FDA and EMA in days and the ratio of approval gap to median control arm time-to-event duration was calculated. A ratio ≥2 implies that, on average, no late domain patients starting treatment in the first half of the gap would be expected to have access to the new drug prior to an event. Results: Of 60 eligible RCTs, 59 had calculable median event durations. 25 (42%) had a primary overall survival endpoint; the most common surrogate endpoint was progression-free survival (PFS; 29/59; 49%). The median (interquartile range [IQR]) approval gap was 186 (124-271) days, with FDA being the first approver in 56/59 (95%) cases. The median (IQR) ratio of approval gap to median control arm event duration was 0.63 (0.35-1.11). Drugs with ratio ≥2 (Table) were targeted or immunotherapies; 7/8 (88%) were approved with PFS endpoint; 5/8 (62.5%) were approved for second line or later. Conclusions: Our study shows that FDA approves most drugs prior to EMA and a nontrivial number of patients may experience progression or death events while awaiting access to anticancer therapies already approved in another domain. The analysis does not take into consideration scenarios in which the new therapy is inferior to SOC or delays in patient access (due to slow uptake; regulatory barriers [in Europe/UK]; or patient affordability [in US]). Further regulatory collaboration (e.g., Project Orbis) between FDA and EMA could help to reduce and potentially ameliorate this differential in access to new cancer drugs in the future. [Table: see text]

11109 Background: scientific community and regulatory agencies have shown a growing interest on QoL, although the inclusion and reporting of QoL analysis in clinical trials is still suboptimal. Methods: we previously published a meta-research study of phase III randomized clinical trial (RCT) in patients with solid neoplasms treated with systemic therapy, published from 2012 to 2021 (BMJ Oncology 2023;2:e000021). For the present analysis, we selected the RCT conducted in the advanced setting, integrating the database with results of QoL and of primary endpoints, and with info about regulatory approval. The main outcome was the analysis of correlation of QoL results with study primary endpoint (EP1), namely overall survival (OS) or progression free survival (PFS). Among secondary outcomes, the availability of QoL results was reported for treatments approved by EMA/FDA, with description of time-trends. Results: 592phase III RCTpublished from 2012 to 2021 were included: 322 (54.4%) published in 2012-2016 and 270 (45.6%) in 2017-2021. 151 RCT (25.5%) were conducted in gastro-intestinal cancers, 138 (23.3%) in thoracic cancers, 71 (12%) in breast cancer, 79 (13.3%) in genito-urinary cancers. Experimental treatment was chemotherapy in 322 studies (54.4%), targeted therapies in 331 (55.9%), immunotherapy in 94 (15.9%) and hormone therapy in 52 (8.8%). OS was the EP1 in 298 clinical trials (50.3%) and PFS in 304 clinical trials (51.4%), with an overlap for 79 studies (13.3%) with multiple primary endpoints. 124 RCT (41.6%) with EP1 OS reported a positive result in EP1. Among these, QoL analysis was positive for experimental treatment in 62 studies (50%), without statistically significant difference or unfavourable in 30 (24.2%) and not available in 32 (25.8%). In the 182 studies (59.5%) with EP1 PFS and a positive result in EP1, QoL analysis was positive for experimental arm in 77 studies (42.3%), without statistically significant difference or unfavourable in 49 (26.9%) and not available in 56 (30.8%). FDA drug approvals were reported for 143 studies (24.2%). Among them, QoL results were positive for experimental arm in 101 studies (70.6%), negative in 19 (13.3%), absent in 23 (16.1%). Similarly, 142 studies (24%) were associated to EMA approval: positive QoL in 101 studies (71.1%), negative in 21 (14.8%) and absent in 20 (14.1%). The percentage of FDA and EMA approvals associated with the availability of positive QoL data increased from 2012-2016 to 2017-2021. Namely, the proportion of approvals with available QoL positive results increased from 56.5% to 81.5% (p<0.001) among FDA approvals, and from 55.4% to 84.4% (p<0.001) among EMA approvals. Conclusions: in many cases, a positivity in OS or PFS is not accompanied by the demonstration of QoL benefit. The temporal trend of positive QoL results among treatments approved by regulatory agencies is encouraging.

As the FDA's drug approval process comes under increasing scrutiny in the US, Health Canada moves closer to beginning concurrent drug reviews with the American regulator. ![Figure][1]</img> Figure. Vioxx was “a profound regulatory failure,” says an official at the FDA Office for Drug Safety

641 Background: Having standardized and high quality reporting of patient reported outcomes (PRO), especially in clinical trials that establish standards of care in oncology is important for patient centered care. This study assessed the status of reporting and quality of analysis of PROs in FDA approved drugs for genitourinary malignancies. Methods: We conducted a systematic review of the FDA archives to identify urological cancer drugs approved between 2007-2018. We retrieved the clinical trials that led to these drug approvals from ClinicalTrials.gov and PubMed. We systematically screened for PROs and reviewed their analytic tools and interpretation methods reported in their published manuscripts and study protocols. A clinical trial was considered to include PROs if they were reported in either the primary or a subsequent manuscript. Results: We identified 22 clinical trials leading to FDA approval of urological cancer drugs between 2007-2018. Only 63% of trials had published PROs. PROs were reported in the primary clinical trial manuscripts for two drugs (9%), and in a secondary PRO manuscript for 12 drugs (54%). The median time between the primary and secondary papers was 12 months (IQR:7.5-26 months). Among the 14 published PRO papers, the hypothesis was broad in 79%, and not reported in 21%. PROs were never included as a primary endpoint of a study. Instead, PROs were reported as secondary endpoints in 5 (36%) and as exploratory endpoints in 7 (50%) studies, while two papers (14%) did not mention PRO reporting in their endpoints. The most common PRO instruments were EQ-5D (64%) and FACT-P (50%). In 92% of PRO papers, statistical analyses were conducted to account for missing data. Control for type I error was needed but not done in 57% of the trials. Conclusions: Delays in publication of PROs occur regularly in trials leading to drug approval in GU malignancies. Our study highlights the need to enhance standardization of the analysis and interpretation of PROs to maximize the value of this data for drug development and approval.

Between 1980 and 2018, novel cancer drug approvals as a percentage share of all novel FDA drug approvals increased from 4.5% to 26.7%.

The legacy is not just with you: an interview with Stephen Baylin.

ImportanceIt is unknown whether and to what degree trials submitted to the US FDA to support drug approval adhere to NCCN guideline-recommended care in their baseline and surveillance CNS imaging protocols.ObjectiveWe sought to characterize the frequency with which the trials cited in US FDA drug approvals for first line advanced NSCLC between 2015 and 2020 deviated from NCCN guideline-recommended care for baseline and surveillance CNS imaging.Design, setting, and participantsRetrospective observational analysis using publicly available data of (1) list of trials cited by the FDA in drug approvals for first line advanced NSCLC from 2015 to 2020 (2) individual trial protocols (3) published trial data and supplementary appendices (4) archived versions of the NCCN guidelines for NSCLC from 2009 to 2018 (the years during which the trials were enrolling).Main outcomes and measuresEstimated percentage of trials for first line advanced NSCLC leading to FDA approval which deviated from NCCN guideline-recommended care with regards to CNS baseline and surveillance imaging.ResultsA total of 14 studies that had been cited in FDA drug approvals for first line advanced NSCLC met our inclusion criteria between January 1, 2015 and September 30, 2020. Of these trials, 8 (57.1%) deviated from NCCN guidelines in their baseline CNS imaging requirement. The frequency of re-assessment of CNS disease was variable amongst trials as well, with 9 (64.3%) deviating from NCCN recommendations.Conclusions and relevanceThe trials supporting US FDA drug approvals in first line advanced NSCLC often have CNS imaging requirements that do not adhere to NCCN guidelines. Many trials permit alternative, substandard methods and the proportion of patients undergoing each modality is uniformly not reported. Nonstandard CNS surveillance protocols are common. To best serve patients with advanced NSCLC in the US, drug approvals by the FDA must be based on trials that mirror clinical practice and have imaging requirements consistent with current US standard of care.

BackgroundSingle-arm clinical trials (SAT) are common in drug and biologic submissions for rare or life-threatening conditions, especially when no therapeutic options exist. External control arms (ECAs) improve interpretation of SATs but pose methodological and regulatory challenges.ObjectiveThrough narrative reviews and expert input, we developed a framework for considerations that might influence regulatory use and likelihood of regulatory acceptance of an SAT, identifying non-oncology first indication approvals as an area of interest. We systematically analyzed FDA and EMA approvals using SATs as pivotal evidence. The framework guided outcome abstraction on regulatory responses.MethodsWe examined all non-oncology FDA and EMA drug and biologic approvals for first indications from 2019 to 2022 to identify those with SAT as pivotal safety or efficacy evidence. We abstracted outcomes, key study design features, regulator responses to SAT and (where applicable) ECA design, and product label content.ResultsAmong 20 SAT-based FDA approvals and 17 SAT-based EMA approvals, most common indications were progressive rare diseases with high unmet need/limited therapeutic options and a natural history without spontaneous improvement. Of the types of comparators, most were natural history cohorts (45% FDA; 47% EMA) and baseline controls (40% FDA; 47% EMA). Common critiques were of non-contemporaneous ECAs, subjective endpoints, and baseline covariate imbalance between arms.ConclusionBased on recent FDA and EMA approvals, the likelihood of regulatory success for SATs with ECAs depends on many design, analytic, and data quality considerations. Our framework is useful in early drug development when considering SAT strategies for evidence generation.

Introduction:The discovery of novel drugs is critical for pharmaceutical research and development as well as for patient treatment. Repurposing existing drugs that may have anticipated effects as potential candidate is one way to meet this important goal. Systematic investigation and comprehensive analysis of approved drugs could provide valuable insights into trends in the discovery and may contribute to further discovery of newer drugs systematically. Food and drug administration (FDA's) Center for Drug Evaluation and Research (CDER) every year summarizes novel drugs, some of which are truly innovative and help in advancing clinical care. This study was conducted to find a trend in drug approvals by FDA in the last 2 decades. Awareness of these new drugs amongst the primary care physicians is also crucial as they have been prescribing these agents in the past.Methodology:In this cross-sectional study, we collected, surveyed, and analyzed drugs approved by U.S. Food and Drug Administration (USFDA) from the year 2000 till 2017 identified from ClinicalTrials.gov and online database of FDA. Drugs approved every year were assessed for total number, class of drug, indication, and category of approval. Type of accelerated regulatory pathways and reasons for speedy approvals every year were also studied. Microsoft Office Excel 2007 was used for tabulation and analysis.Results:Total 209 were approved from 2000 to 2008. Out of these 9.09% were indicated for cardiovascular disorders and 12.91% for neurological disorders. Antibiotics (5.26%) and antivirals (5.74%) were least contributed, whereas anticancer drugs (11.96%) and biologics (7.17%) approval remained constant. Whereas, out of three hundred and two drugs approved during 2009--2017, 5.29% were for cardiovascular disorders, 9.93% for neurological disorders. Antibiotics (5.29%) and antivirals (5.96%) were least in number, whereas anticancer drugs (17.54%) and biologics (15.56%) approval took a steep rise in these years. Also, a wide variation in the number and category of approval was observed over a period of years. The use of fast track, accelerated approval, and priority review programs have also been steadily increasing since 2000.Conclusion:There has been a steady rate of introduction of new drugs by CDER over the last two decades. Expedited approval of anticancer and biologics is seen as recent trend in drug development. Relatively, slow progress in approval of drugs for neurological disorders (depression, psychosis, multiple sclerosis, etc.) and lifestyle diseases like obesity, atherosclerosis, diabetes, etc., were seen. These findings reflect more emphasis being laid down in research for anticancer drugs and biologics.

It is challenging to elucidate the effects of changes in external influences (such as economic or policy) on the rate of US drug approvals. Here, a novel approach—termed the Chronological Hurst Exponent (CHE)—is proposed, which hypothesizes that changes in the long-range memory latent within the dynamics of time series data may be temporally associated with changes in such influences. Using the monthly number FDA’s Center for Drug Evaluation and Research (CDER) approvals from 1939 to 2019 as the data source, it is demonstrated that the CHE has a distinct S-shaped structure demarcated by an 8-year (1939–1947) Stagnation Period, a 27-year (1947–1974) Emergent Period, and a 45-year (1974–2019) Saturation Period. Further, dominant periodicities (resolved via wavelet analyses) are identified during the most recent 45-year CHE Saturation Period at 17, 8 and 4 years; thus, US drug approvals have been following a Juglar/Kuznet mid-term cycle with Kitchin-like bursts. As discussed, this work suggests that (1) changes in extrinsic factors (e.g., of economic and/or policy origin) during the Emergent Period may have led to persistent growth in US drug approvals enjoyed since 1974, (2) the CHE may be a valued method to explore influences on time series data, and (3) innovation-related economic cycles exist (as viewed via the proxy metric of US drug approvals).Supplementary InformationThe online version contains supplementary material available at 10.1007/s43441-021-00279-8.

ObjectivesTo develop and pilot a tool to measure and improve pharmaceutical companies’ clinical trial data sharing policies and practices.DesignCross sectional descriptive analysis.SettingLarge pharmaceutical companies with novel drugs approved by the...

Clinical trial evidence used to support drug approval is typically the only information on benefits and harms that patients and clinicians can use for decision-making when novel cancer therapies become available. Various evaluations have raised concern about the uncertainty surrounding these data, and a systematic investigation of the available information on treatment outcomes for cancer drugs approved by the US Food and Drug Administration (FDA) is warranted. To describe the clinical trial data available on treatment outcomes at the time of FDA approval of all novel cancer drugs approved for the first time between 2000 and 2016. This comparative effectiveness study analyzed randomized clinical trials and single-arm clinical trials of novel drugs approved for the first time to treat any type of cancer. Approval packages were obtained from drugs@FDA, a publicly available database containing information on drug and biologic products approved for human use in the US. Data from January 2000 to December 2016 were included in this study. Regulatory and clinical trial characteristics were described. For randomized clinical trials, summary treatment outcomes for overall survival, progression-free survival, and tumor response across all therapies were calculated, and median absolute survival increases were estimated. Tumor types and regulatory characteristics were assessed separately. Between 2000 and 2016, 92 novel cancer drugs were approved by the FDA for 100 indications based on data from 127 clinical trials. The 127 clinical trials included a median of 191 participants (interquartile range [IQR], 106-448 participants). Overall, 65 clinical trials (51.2%) were randomized, and 95 clinical trials (74.8%) were open label. Of 100 indications, 44 indications underwent accelerated approval, 42 indications were for hematological cancers, and 58 indications were for solid tumors. Novel drugs had mean hazard ratios of 0.77 (95% CI, 0.73-0.81; I2 = 46%) for overall survival and 0.52 (95% CI, 0.47-0.57; I2 = 88%) for progression-free survival. The median tumor response, expressed as relative risk, was 2.37 (95% CI, 2.00-2.80; I2 = 91%). The median absolute survival benefit was 2.40 months (IQR, 1.25-3.89 months). In this study, data available at the time of FDA drug approval indicated that novel cancer therapies were associated with substantial tumor responses but with prolonging median overall survival by only 2.40 months. Approval data from 17 years of clinical trials suggested that patients and clinicians typically had limited information available regarding the benefits of novel cancer treatments at market entry.

872 Background: There were 255 cancer drug approvals by the US Food and Drug Administration (FDA) between January 2020 and October 2024. Although genitourinary (GU) cancers (prostate, urothelial, renal and testicular) compromise some of the most prevalent malignancies, it is unclear how many of these drug approvals were intended for treatment of genitourinary cancers. Methods: Using the list of FDA cancer drug approvals, we identified approvals for GU cancer indications between January 2020 and October 2024. We collected data on tumor type, line of treatment, control arm, primary endpoint(s) as studied in the corresponding clinical trial, and phase of clinical trial. Results: We identified a total of total of 26 drug approvals for GU cancer indications (10.2%) among the total 255 drug approvals for all cancer types. Among these approvals, 12 were for urothelial, 9 for prostate, and 5 for renal. There was variation in the line of setting for each approval’s intended use as shown in the table. No cancer drug approvals were for testicular, penile or adrenal cancer. Most trials were phase III (n = 20), followed by phase II (n = 4) and then one each for phase IB/II and II/III. Overall survival was the most common endpoint (n = 10), followed by response rate and duration of response (n = 7), radiographic progression-free survival (n = 5), disease-free survival (n = 2), and one each for castration rate and metastasis-free survival. Conclusions: Drug approvals for GU cancers compromised approximately 10% of drug approvals by the FDA over the past five years. While OS continues to be the most commonly used endpoint in clinical trials, response rate and duration of response are commonly employed in BCG-refractory non-muscle invasive bladder cancer trials and radiographic progression-free survival in prostate cancer trials. Given the high incidence and mortality from GU cancers, continued drug development is warranted. Intended setting of use for genitourinary cancer drug approvals by tumor type, 2020-2024. Tumor Type Number Indication Urothelial 12 First line (n = 3), adjuvant (n = 1), maintenance (n = 1), BCG-refractory/UTUC (n = 4), second- or later-line (n = 3) Prostate 9 Hormone-sensitive (n = 2), hormone-resistant (n = 1), biochemical recurrence (n = 1), BRCA/HRD mutated (n =5) Renal 5 First-line (n = 2), adjuvant (n = 1), second- or later-line (n = 2) Testicular 0 No applicable Penile 0 Not applicable Adrenal 0 Not applicable 26