Dataset Information

Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs.

ABSTRACT:

Importance

Immunotherapy checkpoint inhibitors have generated considerable interest because of durable responses in a number of hitherto intractable tumor types.

Objective

To estimate the percentage of patients with cancer in the United States who are eligible for and respond to checkpoint inhibitor drugs approved for oncology indications by the US Food and Drug Administration (FDA).

Design, setting, and participants

Retrospective cross-sectional study performed from June 2018 through October 2018 using publicly available data to determine (1) demographic characteristics of patients with advanced or metastatic cancer, (2) FDA data on checkpoint inhibitors approved from January 2011 through August 2018, (3) measures of response from drug labels, and (4) published reports estimating the frequency of various inclusion criteria.

Main outcomes and measures

The estimated percentages of US patients with cancer who are eligible for and who respond to immunotherapy checkpoint inhibitor drugs, by year.

Results

Six checkpoint inhibitor drugs were approved for 14 indications between March 25, 2011, and August 17, 2018. The estimated percentage of patients with cancer who were eligible for checkpoint inhibitor drugs increased from 1.54% (95% CI, 1.51%-1.57%) in 2011 to 43.63% (95% CI, 43.51%-43.75%) in 2018. The percentage of patients with cancer estimated to respond to checkpoint inhibitor drugs was 0.14% (95% CI, 0.13%-0.15%) in 2011 when ipilimumab was approved for unresectable or metastatic melanoma and increased to 5.86% (95% CI, 5.80%-5.92%) by 2015. By 2018, the estimated percentage of responders increased to 12.46% (95% CI, 12.37%-12.54%).

Conclusions and relevance

The estimated percentages of patients who are eligible for and who respond to checkpoint inhibitor drugs are higher than reported estimates for drugs approved for genome-driven oncology but remain modest. Future research should explore biomarkers to maximize the benefit of immunotherapy among patients receiving it.

SUBMITTER: Haslam A

PROVIDER: S-EPMC6503493 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ImportanceWhen a novel drug is granted accelerated approval, both its on-label and off-label uses must be taken into account.ObjectivesTo estimate the potential upper bound of off-label use of erdafitinib to treat advanced cancer with fibroblast growth factor receptor gene (FGFR) alterations, compare it to the upper bound of on-label use in urothelial cancer, and to review studies that may support off-label use.Design, setting, and participantsThis cross-sectional study used frequency data on FGFR alterations by cancer type and the estimated number of deaths from all cancers for 2019 in the United States. Mortality statistics were used as surrogates for patients with advanced cancer. Analysis was conducted in May 2019.ExposurePercentage of patients with an FGFR2 or FGFR3 alteration.Main outcomes and measuresEstimated number of patients with advanced cancer expressing an FGFR2 or FGFR3 alteration eligible for off-label use of erdafitinib by cancer type; number of studies investigating FGFR-targeting drugs for patients with cancer; and number of ongoing clinical trials on erdafitinib by cancer type.ResultsA total of 15 cancer types had reported FGFR alterations. Of 455 440 estimated patients who died of cancer in 2019, 17 019 (3.7%) were estimated to have FGFR2 or FGFR3 alterations. Of these patients, 12 955 (76.1%) could be eligible for off-label treatment with erdafitinib. A total of 29 completed studies evaluated FGFR-targeting drugs in 11 cancer types, and 10 ongoing studies are studying erdafitinib for different oncological indications.Conclusions and relevanceThis study indicates that the potential for off-label use of FGFR inhibitors such as erdafitinib spans a number of cancer types and a large patient population. Systematic trials exploring off-label uses may be desirable for drugs that target clear, identifiable molecular alterations because this may be more efficient than off-label use in identifying clinical scenarios where the agent has activity.

Project description:Background: Prostate cancer is usually considered as immune "cold" tumor with poor immunogenic response and low density of tumor-infiltrating immune cells, highlighting the need to explore clinically actionable strategies to sensitize prostate cancer to immunotherapy. In this study, we investigated whether docetaxel-based chemohormonal therapy induces immunologic changes and potentiates checkpoint blockade immunotherapy in prostate cancer. Methods: We performed transcriptome and histopathology analysis to characterize the changes of prostate cancer immune microenvironment before and after docetaxel-based chemohormonal therapy. Furthermore, we investigated the therapeutic benefits and underlying mechanisms of chemohormonal therapy combined with anti-PD1 blockade using cellular experiments and xenograft prostate cancer models. Finally, we performed a retrospective cohort analysis to evaluate the antitumor efficacy of anti-PD1 blockade alone or in combination with docetaxel-based chemotherapy. Results: Histopathology assessments on patient samples confirmed the enrichment of tumor-infiltrating T cells after chemohormonal therapy. Moreover, we found that docetaxel activated the cGAS/STING pathway in prostate cancer, subsequently induced IFN signaling, resulting in lymphocytes infiltration. In a xenograft mouse model, docetaxel-based chemohormonal therapy prompted the intratumoral infiltration of T cells and upregulated the abundance of PD1 and PD-L1, thereby sensitizing mouse tumors to the anti-PD1 blockade. To determine the clinical significance of these results, we retrospectively analyzed a cohort of 30 metastatic castration-resistant prostate cancer patients and found that docetaxel combined with anti-PD1 blockade resulted in better prostate-specific antigen progression-free survival when compared with anti-PD1 blockade alone. Conclusions: Our study demonstrates that docetaxel activates the antitumoral immune response and facilitates T cell infiltration in a cGAS/STING-dependent manner, providing a combination immunotherapy strategy that would improve the clinical benefits of immunotherapy.

Project description:Importance:To date, the benefit of genome-driven cancer therapy has not been quantified. Objective:We sought to estimate the annual percentage of patients in the United States with advanced or metastatic cancer who could be eligible for and benefit from US Food and Drug Administration (FDA)-approved genome-driven therapy from 2006 to 2018. Design, Setting, and Participants:Retrospective cross-sectional study using publically available data of (1) demographic characteristics of patients with advanced or metastatic cancer; (2) FDA data on cancer drugs approved from January 2006 through January 2018; (3) measures of response and duration of response from drug labels; and (4) published reports estimating the frequency of various genomic aberrations used to estimate what percentage of patients would have been eligible for and would have benefited from genome-driven therapy during the studied period. Main Outcomes and Measures:Estimated percentage of US patients with cancer eligible for and benefiting from genome-targeted and genome-informed therapy by year, response rate of genome-informed indications, and duration of response. Results:A total of 31 drugs with 38 FDA-approved indications met our inclusion criteria for genome-targeted or genome-informed therapy from January 1, 2006, through January 31, 2018. The estimated number of patients eligible for genome-targeted therapy in 2006 was 28 729 of a total 564 830 patients with metastatic cancer, or 5.09% (95% CI, 5.03%-5.14%). By 2018, this number had increased to 50 811 of 609 640, or 8.33% (95% CI, 8.26%-8.40%). For genome-informed therapy in 2006, the eligible number of patients was 59 301 of 564 830, or 10.50% (95% CI, 10.42%-10.58%). In 2018, genome-informed treatment could be offered to 94 157 of 609 640, or 15.44% (95% CI, 15.35%-15.53%) of patients with metastatic cancer. The percentage of patients with cancer estimated to benefit from genome-targeted therapy in 2006 was 0.70% (95% CI, 0.68%-0.72%), and in 2018, it had increased to 4.90% (95% CI, 4.85%-4.95%). For genome-informed treatment in 2006, the percentage estimated to benefit was 1.31% (95% CI, 1.28%-1.34%), and in 2018, it had increased to 6.62% (95% CI, 6.56%-6.68%). The median overall response rate for all genome-informed drugs through January 2018 was 54%, and the median duration of response was 29.5 months. Conclusions and Relevance:Although the number of patients eligible for genome-driven treatment has increased over time, these drugs have helped a minority of patients with advanced cancer. To accelerate progress in precision oncology, novel trial designs of genomic therapies should be developed, and broad portfolios of drug development, including immunotherapeutic and cytotoxic approaches, should be pursued.

Project description:Background Neoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM. Method Under an institutionally approved protocol, we identified adult MM patients with resectable disease who received neoadjuvant anti-PD1 +/- anti-CTLA4 between 2015 to 2019 at our institution. Clinical information include age, gender, presence of nodal involvement or satellitosis, functional status, pre-treatment LDH, tumor mutation status, and treatment data was collected. Outcomes include event free survival (EFS), overall survival (OS), objective response rate (ORR), pathologic response rate (PRR), and grade ≥3 toxicities. Results We identified 36 patients. Median age was 62; 58% were female. Seventy-eight percent of patients received anti-PD1 + anti-CTLA4. Node positive disease or satellite lesions was present at the time of treatment initiation in 47% of patients. Primary sites of disease were anorectal (53%), urogenital (25%), head and neck (17%), and esophageal (6%). A minority of patients did not undergo surgery due to complete response (n=3, 8%) and disease progression (n=6, 17%), respectively. With a median follow up of 37.9 months, the median EFS was 9.2 months with 3-year EFS rate of 29%. Median OS had not been reached and 3-year OS rate was 55%. ORR was 47% and PRR was 35%. EFS was significantly higher for patients with objective response and for patients with pathologic response. OS was significantly higher for patients with pathologic response. Grade 3 toxicities were reported in 39% of patients. Conclusion Neoadjuvant CPI for resectable MM is a feasible approach with signs of efficacy and an acceptable safety profile. As there is currently no standard approach for resectable MM, this study supports further investigations using neoadjuvant therapy for these patients.