scholarly journals Twelve years of European cancer drug approval—a systematic investigation of the ‘magnitude of clinical benefit’

ESMO Open ◽  
2021 ◽  
Vol 6 (3) ◽  
pp. 100166
Author(s):  
N. Grössmann ◽  
S. Wolf ◽  
E. Rothschedl ◽  
C. Wild
Keyword(s):  
Clinical Benefit ◽  
Drug Approval ◽  
Systematic Investigation ◽  
Cancer Drug ◽  
European Cancer

Factors associated with change in the magnitude of clinical benefit of anti-cancer drugs in the post-marketing period.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7052-7052
Author(s):  
Aida Bujosa Rodríguez ◽  
Consolacion Molto ◽  
Thomas J Hwang ◽  
Kerstin Noëlle Vokinger ◽  
Jose Carlos Tapia ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Multivariable Analysis ◽  
Drug Approval ◽  
Cancer Drug ◽  
Marketing Approval ◽  
Cancer Drugs ◽  
Companion Diagnostics ◽  
Substantial Clinical Benefit ◽  
Post Marketing

7052 Background: Initial drug approval is often based on surrogate endpoints. Definitive outcomes like Overall Survival (OS) or Quality of life (QoL) may not be available. Here, we evaluate changes in the magnitude of clinical benefit using the American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) comparing the time of approval to the most recent available data for cancer drugs approved by the US Food and Drug Administration (FDA) between 2006 and 2015. Methods: We examined data on trials supporting FDA accelerated (AA) and regular (RA) cancer drug approvals between January 2006 and December 2015. We performed a systematic search of Pubmed and ClinicalTrials.gov to identify updated OS and/or QoL data, with follow up through April 2019. For AA drugs we analysed initial and confirmatory trials as follow-up. ASCO-VF and ESMO-MCBS grades were applied for trials at approval and after marketing. We explored variables associated with improved clinical benefit scores using multivariable logistic regression. Results: We identified 102 trials supporting the approval of 59 drugs for 96 solid tumour indications. Of these indications, 22 (23%) were granted AA and 21 (95%) were converted to RA. At time of approval, 38% of trials showed improved OS and 17% improved QoL. Substantial clinical benefit was observed in 26% of initial approval trials using ESMO-MCSB and in 34% using ASCO-VF. After a median post-marketing period of 3.3 years, updated results changed substantial clinical benefit in 20 trials with ESMO-MCBS (19 upgrades, 1 downgrade) and in 23 trials using ASCO-VF (19 upgrades, 4 downgrades). For 25% of trials no updated information was found. In the palliative setting, multivariable analysis showed association between improved ASCO-VF scores and initial approvals based on single-arm trials (OR 9.21, 95%CI 1.36-62.29, P=0.023), drugs with companion diagnostics (OR 4.95, 95%CI 1.01-24.22, P=0.049) and second or later lines (OR 7.80, 95%CI 1.35-45.02, P=0.022) while for ESMO-MCBS, drugs with companion diagnostics (OR 6.86, 95%CI 1.82-25.86, P=0.004) and immunotherapy drugs (OR 6.42, 95%CI 1.27-32.59, P=0.025) were associated with greater clinical benefit. Conclusions: Drugs with companion diagnostic tests, immunotherapy as well as approved based on single-arm trials were associated with increased clinical benefit after marketing approval. For a quarter of trials there were no updated data in the post-marketing period.

scholarly journals Progress and Trends for Cancer Drug Approval – an Analysis of FDA Advisory Committee

2012 ◽  
Vol 23 ◽  
pp. ix460
Author(s):  
J.K. Chan ◽  
I. Amanam ◽  
T.K. Kiet ◽  
N. Young-Lin ◽  
D. Hoth ◽  
...  
Keyword(s):  
Advisory Committee ◽  
Drug Approval ◽  
Cancer Drug

scholarly journals Activism and Cancer Drug Approval

2007 ◽  
Vol 3 (5) ◽  
pp. 237-237
Keyword(s):  
Drug Approval ◽  
Cancer Drug

Cancer drug approval criticised

1994 ◽  
Vol &NA; (485) ◽  
pp. 2
Author(s):  
&NA;
Keyword(s):  
Drug Approval ◽  
Cancer Drug

scholarly journals Breast Cancer Drug Approvals Issued by EMA: A Review of Clinical Trials

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5198
Author(s):  
Simona Duranti ◽  
Alessandra Fabi ◽  
Marco Filetti ◽  
Rosa Falcone ◽  
Pasquale Lombardi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Clinical Benefit ◽  
Triple Negative ◽  
Locally Advanced ◽  
Cancer Drug ◽  
European Medicines Agency ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Brca 1

Breast cancer represents the first cause of cancer worldwide and the leading cause of cancer mortality for women. Therefore, new therapies are needed to improve the prognosis of women diagnosed with this disease. In this review, we summarize the new drug indications for the treatment of breast cancer approved by European Medicines Agency between January 2015 and June 2021. In particular, we analyzed the clinical trials results leading to approvals and their update (when available), according to setting (localized and locally advanced or metastatic) and clinical features (hormone receptor positive, HER2 positive, triple negative, BRCA 1/2 mutation). The aim of this paper is to describe the clinical benefit obtained with the new indications.

Fastidious Anatomization of Biota Procured Compounds on Cancer Drug Discovery

2020 ◽  
Vol 21 (5) ◽  
pp. 354-363
Author(s):  
Anand Thirupathi ◽  
Chandra M. Shanmugavadivelu ◽  
Sampathkumar Natarajan
Keyword(s):  
Natural Products ◽  
Side Effects ◽  
Cancer Therapy ◽  
Biological Activities ◽  
Drug Approval ◽  
Current Treatment ◽  
New Drugs ◽  
Cancer Drug ◽  
Synthetic Drugs ◽  
Wide Range

Background: Natural products are the rootstock for identifying new drugs since ancient times. In comparison with synthetic drugs, they have abounding beneficial effects in bestowing protection against many diseases, including cancer. Cancer has been observed as a major threat in recent decades, and its prevalence is expected to increase over the next decades. Also, current treatment methods in cancer therapy such as radiation therapy and chemotherapy cause severe adverse side effects among the cancer population. Therefore, it is exigent to find a remedy without any side effects. Methods: In recent years, research has focused on obtaining naturally derived products to encounter this complication. The current pace of investigations, such as gene identification and advancement in combinatorial chemistry, leads to the aberrant access to a wide range of new synthetic drugs. In fact, natural products act as templates in structure predictions and synthesis of new compounds with enhanced biological activities. Results: Recent developments in genomics have established the importance of polymorphism, which implies that patients require different drugs for their treatment. This demands the discovery of a large number of drugs, but limited sources restrict the pharmaceutical industry to overcome these major obstacles. The use of natural products and their semisynthetic and synthetic analogues could alleviate these problems. However, the lack of standardization in terms of developing methods for evaluating the chemical composition, efficacy, isolation and international approval is still a major limitation in this field. In the past few years, several drug-approval authorities, including the FDA and WHO have allowed using these naturally derived compounds in humans. Conclusion: In this review, we described the use of some natural products from plant and marine sources in cancer treatment and shed some light on semi-synthetic and synthetic compounds derived from natural sources used in cancer therapy.

Overall survival, quality of life and magnitude of clinical benefit of breast cancer drugs over the last 25 years.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6571-6571
Author(s):  
J. Carlos Tapia ◽  
Aida Bujosa Rodríguez ◽  
Consolacion Molto ◽  
Arnoud J. Templeton ◽  
Daniel Shepshelovich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Benefit ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Curative Intent ◽  
Substantial Clinical Benefit ◽  
Breast Cancer Drugs ◽  
Palliative Setting ◽  
Over Time

6571 Background: The American Society of Clinical Oncology Cancer Research Committee (ASCO-CRC), the ASCO Value Framework Net Health Benefit score version 2 (ASCO-VF), and the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) are validated tools quantifying the clinical benefit for cancer drugs. Here, we assess the overall survival (OS), quality of life (QoL) and magnitude of clinical benefit of trials supporting breast cancer drug approval by the US Food and Drug Administration (FDA) in the last 25 years. Methods: We searched Drugs@FDA website for all breast cancer drug approvals from January 1, 1995 to December 30, 2020. Drug labels and reports of registration trials were reviewed. We collected data on trial characteristics, efficacy, toxicity and QoL. When more than one study supported a single indication, we preferred efficacy-oriented endpoints (typically OS) to QoL. We excluded trials supporting accelerated-approval indications if these were converted to regular approval during the study period. We scored clinical benefit using the ASCO-CRC in palliative setting, and ASCO-VF and ESMO-MCBS in both curative and palliative setting. Substantial clinical benefit was defined as: OS gains ≥2.5 months and progression-free survival gains ≥ 3 months for ASCO-CRC criteria; ASCO-VF scores ≥ 45 and grade of A or B for trials of curative intent and 4 or 5 for those of non-curative intent using ESMO-MCBS. Trends over time were assessed using Chi-squared test for trend. Results: We identified 51 trials supporting the approval of 32 individual drugs for 51 indications; 12 (24%) were in the curative setting and 39 (76%) in the palliative setting. At the time of approval, 8 (16%) trials reported significant improvement in OS. QoL was reported in 22 trials (43%). Among these, 8 (36%) showed improvement in QoL. For curative intent, we applied ASCO-VF and ESMO-MCBS score to 11 (92%) trials, finding clinical benefit in 10 (91%) and 2 (18%) trials, respectively. In the palliative setting, we used ASCO-CRC, ASCO-VF and ESMO-MCBS scores to rate 32 (82%), 33 (85%) and 38 (97%) trials. Substantial clinical benefit was observed in 20 (63%), 12 (36%) and 7 (19%) trials, respectively. Over time, there has been a decrease in the number of trials supporting approval based on OS (1996-2003 50% vs 2004-12 38% vs 2013-20 13%, P trend = 0.033). There were no statistically significant changes over time in QoL, ASCO-CRC, ASCO-VF and ESMO-MCBS scores. Conclusions: For palliative intent, most trials supporting FDA approval of breast cancer drugs do not meet the ASCO-VF or ESMO-MCBS criteria for substantial clinical benefit. There is substantial inter-framework variability in the assessment of clinical benefit in the curative setting. Over time, there has been a substantial shift towards use of surrogate endpoints as the basis for approval without a clear improvement in substantial clinical benefit.

Use of single-arm trials to support malignant hematology and oncology drug and biologic approvals: A 20-year FDA experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13572-e13572
Author(s):  
Sundeep Agrawal ◽  
Shaily Arora ◽  
Jonathon Joseph Vallejo ◽  
Thomas Gwise ◽  
Meredith Kathleen Chuk ◽  
...  
Keyword(s):  
Drug Development ◽  
Clinical Benefit ◽  
Randomized Clinical Trials ◽  
Kinase Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Oncology Drug

e13572 Background: Improved understanding of the underlying biology of cancer has led to a paradigm shift in cancer drug development and has paved the way for many products to receive accelerated or regular approval based on non-randomized/single arm trials (SATs). Given the high unmet medical need of cancer patients, challenges with lengthy and confounded survival endpoints, and difficulty enrolling rare biomarker-defined subsets of disease, SATs have been used to evaluate a variety of cancer therapies. Unlike time to event endpoints, the objective and clinically relevant endpoint of response rate (RR) and duration of response is interpretable in SATs, as spontaneous tumor shrinkage is not expected. Methods: A search of FDA databases identified all drugs and biologics approved for malignant hematology and oncology indications from January 1, 2001, to December 31, 2020 based on SATs. Data sources included approval letters, U.S. prescribing information, and clinical review documents. The definition of response varied by setting and time period (e.g. RECIST, WHO, IWG, etc.). Results: Between January 1, 2001 and December 31, 2020, FDA granted 153 new indications based on SATs, including 102 accelerated approvals (AAs) and 51 regular approvals (RAs). Overall, 69 approvals (45%) were for new molecular entities and 84 (55%) were expanded indications. Response rate was the most common endpoint used in the trial providing substantial evidence of efficacy to support approval [120/153, (78%)]. The durability of response was also considered to support evidence of clinical benefit. Of the 102 AAs, 38 (37%) have fulfilled their post-marketing requirement (PMR) to verify clinical benefit, 59 (58%) are pending verification of benefit, and 5 (5%) have been withdrawn from the market. Of note, 88% (52/59) of AAs pending verification of benefit occurred in the last 5 years alone (22 AAs in 2020, 8 in 2019, 8 in 2018, 12 in 2017, and 2 in 2016). Between 2001-2020, 58 (38%) new indications were granted for kinase inhibitors, 34 (22%) for immune checkpoint inhibitors (CPIs), and 61 (40%) for drugs with other mechanisms of action including but not limited to antibody-drug conjugates, cytotoxic drugs, and non-CPI monoclonal antibodies. Conclusions: In the last two decades, SATs have been effectively used to study anti-cancer therapies in well-defined patient populations using durable RR as an objective and interpretable clinical endpoint. Although randomized clinical trials remain the gold standard in clinical research, SATs have allowed for rapid advancements in oncology drug development and will continue to serve an important role in bringing new therapies to patients with unmet need.

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