FDA Approval Summary: Nadofaragene firadenovec-vncg for bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer.

On December 16, 2022, the FDA approved the adenoviral vector-based gene therapy nadofaragene firadenovec-vncg (brand name Adstiladrin) for the treatment of adult patients with high-risk bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The product represents the first approved adenoviral vector-based gene therapy and the first approved gene therapy for bladder cancer. Determination of efficacy was based on results from Study rAd-IFN-CS-003 (Study CS-003), a single-arm trial in 98 evaluable patients with BCG-unresponsive NMIBC with CIS who received intravesical instillations of the gene therapy product (75 mL of nadofaragene firadenovec at 3 × 1011 viral particles per mL) once every 3 months.

Review of Racial and Ethnic Representation of Participants Enrolled in Pediatric Clinical Trials of Oncology Drugs Conducted Through FDA Written Requests.

Importance: The Best Pharmaceuticals for Children Act states that in issuing a written request (WR), the US Food and Drug Administration (FDA) shall consider the adequate representation (eg, proportionate to the disease population) of children from racial and ethnic minority populations. If the terms of the WR are fulfilled, the FDA may grant an additional 6 months of exclusivity for any unexpired patents and exclusivities attached to approved indications.

Objective: To report on the race and ethnicity of participants enrolled in pediatric studies conducted in response to WRs for which pediatric exclusivity was granted between 2001 and 2021.

Highlights of FDA Oncology Approvals in 2023: Bispecific T-cell Engagers, Pediatric Indications, and Inclusive Drug Development.

Cancer drug development remained robust in 2023. Highlights of U.S.

State of Cancer Care in America: Achieving Cancer Health Equity Among Sexual and Gender Minority Communities.

In 2017, ASCO issued the position statement, Strategies for Reducing Cancer Health Disparities Among Sexual and Gender Minority Populations, outlining five areas of recommendations to address the needs of both sexual and gender minority (SGM, eg, LGBTQ+) populations affected by cancer and members of the oncology workforce who identify as SGM: (1) patient education and support; (2) workforce development and diversity; (3) quality improvement strategies; (4) policy solutions; and (5) research strategies. In 2019, ASCO convened the SGM Task Force to help actualize the recommendations of the 2017 position statement. The percentage of the US population who publicly identify as SGM has increased dramatically over the past few years.

FDA Approval Summary: Tremelimumab in Combination with Durvalumab for the Treatment of Patients with Unresectable Hepatocellular Carcinoma.

On October 21, 2022, the FDA approved tremelimumab (Imjudo) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma. The approval was based on the results from the HIMALAYA study, in which patients with unresectable hepatocellular carcinoma who were naïve to previous systemic treatment were randomly assigned to receive one of three study arms: tremelimumab in combination with durvalumab (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The primary objective of improvement in overall survival (OS) for tremelimumab in combination with durvalumab compared with sorafenib met statistical significance with a stratified HR of 0.

Researcher Experience and Comfort With Telemedicine and Remote Patient Monitoring in Cancer Treatment Trials.

Background: Since the onset of COVID-19, oncology practices across the US have integrated telemedicine (TM) and remote patient monitoring (RPM) into routine care and clinical trials. The extent of provider experience and comfort with TM/RPM in treatment trials, however, is unknown. We surveyed oncology researchers to assess experience and comfort with TM/RPM.

Driving Diversity and Inclusion in Cancer Drug Development - Industry and Regulatory Perspectives, Current Practices, Opportunities, and Challenges.

In April 2022, the FDA issued draft guidance to help industry develop strategies to improve diversity in clinical trials. Historically, clinical trial sponsors have not systematically incorporated efforts to promote diversity, equity, and inclusion (DEI), particularly during the early design stages of clinical development plans and operational strategies. Unfortunately, a retrospective approach to DEI often results in clinical trial participants not being reflective of the diversity of patients intended to be treated with new therapies.

FDA Approval Summary: Tucatinib with Trastuzumab for Advanced Unresectable or Metastatic, Chemotherapy Refractory, HER2-Positive RAS Wild-Type Colorectal Cancer.

On January 19, 2023, the FDA granted accelerated approval to tucatinib in combination with trastuzumab for the treatment of patients with unresectable or metastatic RAS wild-type, HER2-positive colorectal cancer who have received prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan. Approval was based on the pooled analysis of patients receiving tucatinib in combination with trastuzumab in MOUNTAINEER (NCT03043313), an open-label, multicenter trial. The primary endpoint was overall response rate (ORR) by RECIST 1.

FDA Approval Summary: Futibatinib for Unresectable Advanced or Metastatic, Chemotherapy Refractory Intrahepatic Cholangiocarcinoma with FGFR2 Fusions or Other Rearrangements.

On September 30, 2022, the FDA granted accelerated approval to futibatinib for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions or other rearrangements. Approval was based on Study TAS-120-101, a multicenter open-label, single-arm trial. Patients received futibatinib 20-mg orally once daily.

FDA Analysis of Ineligibility for Acute Myeloid Leukemia Clinical Trials by Race and Ethnicity.

Background: Patients of certain racial and ethnic groups have been underrepresented in clinical trials for treatment of malignancy. One potential barrier to participation is entry requirements that lead to patients in various racial and ethnic groups not meeting eligibility criteria for studies (ie, "screen failure"). The objective of this study was to analyze the rates and reasons for trial ineligibility by race and ethnicity in trials of acute myeloid leukemia (AML) submitted to the U.

FDA Approval Summary: Ripretinib for Advanced Gastrointestinal Stromal Tumor.

On May 15, 2020, the FDA approved ripretinib for adult patients with advanced gastrointestinal stromal tumor who have received prior treatment with three or more kinase inhibitors, including imatinib. The approval was based on results from INVICTUS (NCT03353753), an international, multi-center, double-blind, placebo-controlled trial. Patients were randomly allocated (2:1) to receive either ripretinib 150 mg once daily (n = 85) or matching placebo (n = 44).

FDA Approval Summary: Pemigatinib for Previously Treated, Unresectable Locally Advanced or Metastatic Cholangiocarcinoma with FGFR2 Fusion or Other Rearrangement.

On April 17, 2020, the FDA granted accelerated approval to pemigatinib (PEMAZYRE, Incyte Corporation) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement as detected by an FDA-approved test. Approval was based on FIGHT-202 (NCT02924376), a multicenter open-label single-arm trial. Efficacy was based on 107 patients with locally advanced unresectable or metastatic cholangiocarcinoma whose disease had progressed on or after at least one prior therapy and had an FGFR2 gene fusion or rearrangement.

FDA Approval Summary: Nivolumab for the Adjuvant Treatment of Adults with Completely Resected Esophageal/Gastroesophageal Junction Cancer and Residual Pathologic Disease.

The FDA approved nivolumab on May 20, 2021, for the adjuvant treatment of completely resected (negative margins) esophageal or gastroesophageal junction cancer (EC/GEJC) in patients who had residual pathologic disease following chemoradiotherapy. The approval was based on data from the double-blind CheckMate 577 trial, which randomly allocated patients to receive nivolumab or placebo. Disease-free survival (DFS) was the primary endpoint.

Exploring racial disparities in treatment patterns and outcomes for patients with multiple myeloma using real world data.

This retrospective observational study evaluated racial disparities among Black and White patients with multiple myeloma (MM). We included patients from a longitudinal de-identified EHR-derived database who had ≥2 visits recorded on or after 1/1/2011, documented treatment, and race listed as White or Black. Black patients (n = 1172) were more likely female (54.

FDA Approval Summary: Ivosidenib for the Treatment of Patients with Advanced Unresectable or Metastatic, Chemotherapy Refractory Cholangiocarcinoma with an IDH1 Mutation.

On August 25, 2021, the FDA approved ivosidenib for the treatment of adult patients with unresectable locally advanced or metastatic hepatocellular isocitrate dehydrogenase 1 (IDH1) mutated cholangiocarcinoma (CCA) as detected by an FDA-approved test with disease progression after 1 to 2 prior lines of systemic therapy for advanced disease. The approval was based on data from Study AG120-C-005 (ClarIDHy), a double-blind placebo-controlled trial that randomly allocated (2:1) patients to receive either ivosidenib or placebo. Independently assessed progression-free survival (PFS) was the primary endpoint.

Analysis of racial and ethnic disparities in multiple myeloma US FDA drug approval trials.

African Americans (AAs) have a higher incidence of multiple myeloma (MM) than White patients. Mortality is also higher in AAs compared with White patients. AAs more commonly have immunoglobulin H translocations t(11;14) and t(14;16) compared with White patients.

Subgroup Analyses in Oncology Trials: Regulatory Considerations and Case Examples.

Subgroup analyses are assessments of treatment effects based on certain patient characteristics out of the total study population and are important for interpretation of pivotal oncology trials. However, appropriate use of subgroup analyses results for regulatory decision-making and product labeling is challenging. Typically, drugs approved by the FDA are indicated for use in the total patient population studied; however, there are examples of restriction to a subgroup of patients despite positive study results in the entire study population and also extension of an indication to the entire study population despite positive results appearing primarily in one or more subgroups.

FDA Approval Summary: Pembrolizumab for the Treatment of Tumor Mutational Burden-High Solid Tumors.

The FDA approved pembrolizumab on June 16, 2020, for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high [TMB-H; ≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. FDA granted the approval based on a clinically important overall response rate (29%; 95% confidence interval, 21-39) and duration of response (57% of responses lasting ≥ 12 months) in the subset of patients with TMB-H solid tumors ( = 102) spanning nine different tumor types enrolled in a multicenter single-arm trial (KEYNOTE-158). The efficacy of pembrolizumab was supported by the results of whole-exome sequencing (WES) analyses of TMB in additional patients enrolled across multiple pembrolizumab clinical trials, and a scientific understanding of the effects of PD-1 inhibition.

New patient-centered care standards from the commission on cancer: opportunities and challenges.

The Commission on Cancer of the American College of Surgeons publishes accreditation standards that hospitals and cancer treatment centers implement to ensure quality care to cancer patients. These standards address the full spectrum of cancer care, from cancer prevention to survivorship and end-of-life care. The most recent revisions of these standards included new standards in "patient-centered areas," including the provision of palliative care services, treatment and survivorship plans, psychological distress screening, and patient navigation programs.