Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer.

OBJECTIVE: To evaluate adverse events (AEs) of combination lenvatinib plus pembrolizumab for the treatment of recurrent endometrial cancer (EC) and to assess outcomes by lenvatinib starting dose. METHODS: We retrospectively reviewed patients with recurrent EC treated with lenvatinib plus pembrolizumab at our institution between 10/1/2019-11/30/2021. Starting dose of lenvatinib was defined as standard (20 mg) or reduced (10 mg/14 mg). AEs were manually extracted through chart review and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. PFS, overall survival (OS), and duration of response (DOR) were analyzed. RESULTS: Forty-three patients were identified; median age was 67 years (range, 54-85). The most common histologies were serous (35%), endometrioid (23%), and carcinosarcoma (21%). Starting lenvatinib doses were 10 mg (n = 10), 14 mg (n = 10), and 20 mg (n = 23). Median number of cycles received was 8 (range, 1-42). Twenty-four patients (56%) required ≥1 lenvatinib dose reduction; 3 (7%) discontinued lenvatinib, and 1 (2%) discontinued pembrolizumab for intolerance or AE. Thirty-six patients (84%) experienced grade ≥ 3 AEs; hypertension, weight loss, anemia, fatigue, and thrombocytopenia were most common. The standard dose group experienced significantly shorter observed PFS vs the reduced dose group (P = .02). There was no difference in DOR (P = .09) or OS (P = .27) between the groups. CONCLUSION: In clinical practice, AEs associated with combination lenvatinib plus pembrolizumab were common and comparable to Study 309/KEYNOTE-775 findings. AEs were similar regardless of starting lenvatinib dose. Further dose optimization studies of lenvatinib plus pembrolizumab may be indicated in recurrent EC. Clinical trial data remain the gold standard to guide starting lenvatinib dosing.

Current Evidence-Based Systemic Therapy for Advanced and Recurrent Endometrial Cancer.

Endometrial cancer (EC) is the most common gynecologic malignancy, with worldwide increasing incidence and disease-associated mortality. Although most patients with EC are diagnosed with early-stage disease, systemic treatment options for patients with advanced or recurrent EC have historically been limited. EC-focused clinical trials and the ensuing therapeutic landscape have expanded since The Cancer Genome Atlas (TCGA) identified 4 distinct EC subgroups associated with differential survival. This endeavor revolutionized our understanding of the genomic characterization of EC as well as molecular drivers of this heterogeneous malignancy, leading to precision oncology approaches to therapeutics and advancement in treatment options. This review describes the current status of and recent advancements in therapeutic options for patients with advanced and recurrent EC. The NCCN Guidelines for Uterine Neoplasms provide detailed recommendations regarding the diagnosis, workup, and management of EC.

Clinical Trial Participation Among Older Adult Medicare Fee-for-Service Beneficiaries With Cancer.

Importance: Clinical trials play a critical role in the development of novel cancer therapies, and precise estimates of the frequency with which older adult patients with cancer participate in clinical trials are lacking. Objective: To estimate the proportion of older adult Medicare Fee-for-Service (FFS) beneficiaries with cancer who participate in interventional cancer clinical trials, using a novel population-based methodology. Design, Setting, and Participants: In this retrospective cohort study evaluating clinical trial participation among older adult patients with cancer from January 1, 2014, through June 30, 2020, claims data from Medicare FFS were linked with the ClinicalTrials.gov to determine trial participation through the unique National Clinical Trial (NCT) identifier. The proportion of patients with newly diagnosed or newly recurrent cancer in 2015 participating in an interventional clinical trial and receiving active cancer treatment from January 2014 to June 2020 was estimated. Data analysis was performed from November 18, 2020, to November 1, 2021. Exposures: Patients with cancer aged 65 years or older with Medicare FFS insurance, with and without active cancer treatment. Main Outcomes and Measures: Enrollment in clinical trials among all patients with cancer 65 years and older and among patients receiving active cancer treatments as defined by the presence of at least 1 NCT identifier corresponding to an interventional cancer clinical trial in Medicare claims. Results: Among 1 150 978 patients (mean [SD] age, 75.7 [8.4] years; 49.9% men and 50.1% women) with newly diagnosed or newly recurrent cancer in 2015, 12 028 (1.0%) patients had a billing claim with an NCT identifier indicating enrollment in an interventional cancer clinical trial between January 2014 and June 2020. In a subset of 429 343 patients with active cancer treatment, 8360 (1.9%) were enrolled in 1 or more interventional trials. Patients enrolled in a trial tended to be younger, male, a race other than Black, and residing in zip codes with high median incomes. Conclusions and Relevance: Findings of this cohort study show that clinical trial enrollment among older adult patients with cancer remains low, with only 1.0% to 1.9% of patients with newly diagnosed or recurrent cancer in 2015 participating in an interventional cancer clinical trial as measured by the presence of NCT identifiers in Medicare claims. These data provide a contemporary estimate of trial enrollment, persistent disparities in trial participation, and only limited progress in trial access over the past 2 decades.

Despite The FDA's Five-Year Plan, Black Patients Remain Inadequately Represented In Clinical Trials For Drugs.

For decades Black patients have been underrepresented in clinical trials of new treatments. In response, in 2015 the Food and Drug Administration (FDA) launched a five-year action plan aimed at improving diversity in and transparency of pivotal clinical trials for newly approved drugs. The plan contained many action steps that were aimed at improving the racial representativeness of clinical trials and enhancing the reporting of new drug side effects and benefits across diverse populations. Yet, relying on the FDA's Drug Trials Snapshots website, we failed to find evidence that the action plan improved representation of Black trial participants. Black patients remained inadequately represented in clinical trials for drugs, with a median of one-third the enrollment that would be required, whether the trials were started before, during, or after the action plan. Fewer than 20 percent of drugs had data regarding treatment benefits or side effects reported for Black patients; neither measure improved during the action plan period.

Validation of a Population-Based Data Source to Examine National Cancer Clinical Trial Participation.

Importance: The Centers for Medicare & Medicaid Services requires health care organizations to report the National Clinical Trial (NCT) identifier on claims for items and services related to clinical trials that qualify for coverage. This same NCT identifier is used to identify clinical trials in the ClinicalTrials.gov registry. If linked, this information could facilitate population-based analyses of clinical trial participation and outcomes. Objective: To evaluate the validity of a linkage between fee-for-service (FFS) Medicare claims and ClinicalTrials.gov through the NCT identifier for patients with cancer enrolled in clinical trials. Design, Setting, and Participants: This cohort study included 2 complementary retrospective analyses for a validation assessment. First, billing data from 3 health care institutions were used to estimate the missingness of the NCT identifier in claims by calculating the proportion of known participants in cancer clinical trials with no NCT identifier on any submitted Medicare claims. Second, the Surveillance Epidemiology and End Results-Medicare data set, which includes a subset of all FFS Medicare beneficiaries for whom health insurance claims are linked with cancer registry data, was used to identify adult patients diagnosed with cancer between 2006 and 2015 with an NCT identifier in claims corresponding to an interventional cancer clinical trial. To estimate the accuracy of the NCT identifier when present, the proportion of NCT identifiers that corresponded to trials that were aligned with the patients' known primary or secondary diagnoses was calculated. Data were analyzed from March 2020 to March 2021. Exposures: An NCT identifier present in Medicare claims. Main Outcomes and Measures: The main outcome was participating in a clinical trial relevant to patient's cancer diagnosis. Results: A total of 1 171 816 patients were included in analyses. Across the 3 participating institutions, there were 5061 Medicare patients enrolled in a clinical trial, including 3797 patients (75.0%) with an NCT identifier on at least 1 billing claim that matched the clinical trial on which the patient was participating. Among 1 171 816 SEER-Medicare patients, 29 138 patients (2.5%) had at least 1 claim with a value entered in the NCT identifier field corresponding to 32 950 unique patient-NCT identifier pairs. There were 26 694 pairs (81.0%) with an NCT identifier corresponding to a clinical trial registered in ClinicalTrials.gov, of which 10 170 pairs (38.1%) were interventional cancer clinical trials. Among these, 9805 pairs (96.4%) were considered appropriate. Conclusions and Relevance: In this cohort study, this data linkage provided a novel data source to study clinical trial enrollment patterns among Medicare patients with cancer on a population level. The presence of the NCT identifiers in claims for Medicare patients participating in clinical trials is likely to improve over time with increasing adherence with the Centers for Medicare & Medicaid Services mandate.

Virtual Mind-Body Programming for Patients With Cancer During the COVID-19 Pandemic: Qualitative Study.

BACKGROUND: Patients with cancer are particularly vulnerable to stress and anxiety during the COVID-19 pandemic. Social distancing is critical for patients with cancer; however, it can also reduce their access to psychosocial coping resources. OBJECTIVE: The aim of this study was to explore patient experiences to generate a model of how virtual mind-body programs can support the psychosocial well-being of patients with cancer. METHODS: We conducted a qualitative study among patients (aged ≥18 years) who participated in a virtual mind-body program offered by a National Cancer Institute-designated Comprehensive Cancer Center during the COVID-19 pandemic. The program consisted of mind-body group therapy sessions of fitness, yoga, tai chi, dance therapy, music therapy, and meditation. Live integrative medicine clinicians held each session via Zoom videoconferencing for 30-45 minutes. In semistructured phone interviews (n=30), patients were asked about their overall impressions and perceptions of the benefits of the sessions, including impacts on stress and anxiety. Interviews were analyzed using grounded theory. RESULTS: Among the 30 participants (average age 64.5 years, SD 9.36, range 40-80, 29 female), three major themes were identified relating to experiences in the virtual mind-body program: (1) the sessions helped the patients maintain structured routines and motivated them to adhere to healthy behaviors; (2) the sessions enhanced coping with COVID-19-related-stressors, allowing patients to "refocus" and "re-energize"; and (3) the sessions allowed patients to connect, fostering social relationships during a time of isolation. These themes informed the constructs of a novel behavioral-psychological-social coping model for patients with cancer. CONCLUSIONS: Virtual mind-body programming supported patients with cancer during the COVID-19 pandemic through a behavioral-psychological-social coping model by enhancing psychological coping for external stressors, supporting adherence to motivation and health behaviors, and increasing social connection and camaraderie. These programs have potential to address the behavioral, psychological, and social challenges faced by patients with cancer during and beyond the COVID-19 pandemic. The constructs of the conceptual model proposed in this study can inform future interventions to support isolated patients with cancer. Further clinical trials are needed to confirm the specific benefits of virtual mind-body programming for the psychosocial well-being and healthy behaviors of patients with cancer.

Assessment of Outcomes Associated With the Use of Newly Approved Oncology Drugs in Medicare Beneficiaries.

Importance: A lack of generalizability of pivotal cancer clinical trial data to treatment of older adults with Medicare could affect therapeutic decision-making in clinical practice. Objective: To evaluate the differences in survival, duration of therapy, and treatment patterns between clinical trial patients and older adults with Medicare receiving cancer drugs for metastatic solid cancers in usual practice. Design, Setting, and Participants: This retrospective cohort study, performed from May 1, 2018, to August 30, 2020, used the linked Surveillance, Epidemiology, and End Results (SEER) program and Medicare database to examine sequential US Food and Drug Administration (FDA)-approved cancer drug indications (2008-2013) for locally advanced or metastatic solid tumors to assess whether pivotal trials reflect the outcomes of Medicare patients with cancer treated in usual practice. Exposures: Treatment with FDA-approved cancer drugs for metastatic solid cancers in pivotal clinical trials and in the SEER-Medicare database. Main Outcomes and Measures: Overall survival, duration of treatment, and dose reductions among trial participants and treated Medicare patients. Results: A total of 11 828 trial participants (mean age, 61.8 years; 6718 [56.8%] male; and 7605 [64.3%] White) and 9178 SEER-Medicare patients (mean age, 72.7 years; 4800 [52.3%] male; and 7437 [81.0% White]) were compared. Twenty-nine indications for 22 cancer drugs were included. Median overall survival among Medicare patients was shorter than among patients in the clinical trial intervention arm for 28 of 29 indications (median difference, -6.3 months; range, -28.7 to 2.7 months). Median duration of therapy among Medicare patients was shorter for 23 of the 27 indications with data available (median difference, -1.9 months; range, -12.4 to 1.4 months). For 9 indications, there was information available regarding dose reductions in the package insert or trial publication. In all but 1 instance, dose reductions or single prescriptions were more common in the Medicare population compared with dose reductions among the clinical trial patients; for example, in the Medicare patients, 600 of 1032 (58.1%) received dose reduction or a single prescription and 172 of 1032 (16.7%) received a single prescription vs 734 of 3416 (21.5%) in the trial intervention arm. The exception was afatinib for non-small cell lung cancer: 34 of 71 (47.9%) received dose reduction or a single prescription and 15 of 71 (21.1%) received a single prescription among the Medicare patients vs 120 of 230 (52.2%) receiving dose reductions among the trial intervention group. Conclusions and Relevance: In this cohort study, patients receiving Medicare who were treated with FDA-approved cancer drugs did not live as long as treated clinical trial participants and commonly received treatment modifications. This study suggests that cancer clinical data relevant to newly approved drugs lack generalizability to Medicare beneficiaries with cancer; therefore, these agents should be used with caution.

Impact of provider volume on front-line chemotherapy guideline compliance and overall survival in elderly patients with advanced ovarian cancer.

PURPOSE: We sought to evaluate whether provider volume or other factors are associated with chemotherapy guideline compliance in elderly patients with epithelial ovarian cancer (EOC). METHODS: We queried the SEER-Medicare database for patients ≥66 years, diagnosed with FIGO stage II-IV EOC from 2004 to 2013 who underwent surgery and received chemotherapy within 7 months of diagnosis. We compared NCCN guideline compliance (6 cycles of platinum-based doublet) and chemotherapy-related toxicities across provider volume tertiles. Factors associated with guideline compliance and chemotherapy-related toxicities were assessed using logistic regression. Overall survival (OS) was compared across volume tertiles and Cox proportional-hazards model was created to adjust for case-mix. RESULTS: 1924 patients met inclusion criteria. The overall rate of guideline compliance was 70.3% with a significant association between provider volume and compliance (64.5% for low-volume, 72.2% for medium-volume, 71.7% for high-volume, p = .02). In the multivariate model, treatment by low-volume providers and patient age ≥ 80 years were independently associated with worse chemotherapy-guideline compliance. In the survival analysis, there was a significant difference in median OS across provider volume tertiles with median survival of 32.8 months (95%CI 29.6, 36.4) low-volume, 41.9 months (95%CI 37.5, 46.7) medium-volume, 42.1 months (95%CI 38.8, 44.2) high-volume providers, respectively (p < .01). After adjusting for case-mix, low-volume providers were independently associated with higher rates of mortality (aHR 1.25, 95%CI: 1.08, 1.43). CONCLUSIONS: In a modern cohort of elderly Medicare patients with advanced EOC, we found higher rates of non-compliant care and worse survival associated with treatment by low-volume Medicare providers. Urgent efforts are needed to address this volume-outcomes disparity.

Trends in Female Representation on NCCN Guideline Panels.

BACKGROUND: NCCN produces highly influential disease-specific oncology clinical practice guidelines. Because the number of women in academic oncology has increased, we assessed whether the composition of NCCN Guidelines Panels reflected this trend. METHODS: Using historical guidelines requested from NCCN, we investigated time trends for female representation on 21 NCCN Guidelines Panels and analyzed the trends for female-predominant cancers (breast, ovarian, uterine, and cervical) compared with all cancers. RESULTS: From 2013 to 2019, there was an increase from 123 women of 541 total panelists (22.7%) to 175 women of 542 panelists (32.3%). Within the 4 female-predominant cancers, the increase was more rapid: from 30 of 101 total panelists (29.7%) to 66 of 118 panelists (56.4%). Excluding female-predominant cancers, increases were minimal. CONCLUSIONS: There could be multiple explanations for these differing trends, including the possibility of more rapid increases in the underlying pool of female physician-scientists in female-predominant specialties or more efforts to increase the representation of women in decisions about the standard of care in cancers predominantly affecting women.

Short Peripheral Catheter Dwell Time and Associated Complications: A Systematic Review.

There is evidence that the risk of complications caused by short peripheral catheters (SPCs) does not increase when SPCs are replaced due to clinical indication versus at a specific time frame. In the studies, however, the dwell time does not typically exceed an average of 3.5 days. It is uncertain how long SPCs may stay in place before there is an increased risk for complications or if there is an increased risk. This systematic review was conducted to explore the current state of the science regarding SPC dwell time as a predictor of SPC complications in adult inpatients.

Impact of Provider Imaging Practices on Survival Outcomes in Advanced Ovarian Cancer.

BACKGROUND: This study sought to describe how high- versus low-frequency surveillance imaging practices among providers at Memorial Sloan Kettering Cancer Center (MSKCC) impact overall survival (OS) and time to recurrence of patients with advanced epithelial ovarian cancer in first remission. METHODS: The study cohort included patients with stage II-IV high-grade epithelial ovarian cancer diagnosed in January 2001 through January 2017 who experienced recurrence after initial platinum-based chemotherapy. To determine usual imaging practices for providers at MSKCC, median frequency of CT or MRI of the abdomen/pelvis was calculated among patients with a long-term remission (defined as at least 1 year) treated by each provider. Cox proportional hazards models were used to examine differences in OS and time to recurrence among patients treated by providers with high versus low imaging frequency practices, with additional subgroup analysis among patients with elevated CA-125 levels >35 U/mL at diagnosis. Chi-square tests were used to examine differences in the proportion of patients who enrolled in clinical trials or underwent secondary cytoreductive surgery (SCS) by imaging frequency. RESULTS: A total of 543 patients were treated by providers with high imaging frequency (>1 scan every 12 months) and 141 were treated by providers with low imaging frequency (≤1 scan every 12 months). Time to recurrence was shorter among patients treated by providers with high versus low imaging frequency (18.0 vs 19.2 months; hazard ratio, 1.33; P=.003). Results were similar when restricted to patients with elevated CA-125 levels at diagnosis. There was no significant difference in OS, clinical trial enrollment, or SCS by imaging practice. CONCLUSIONS: Within the limitations of this retrospective analysis, patients with advanced ovarian cancer treated by high-frequency-imaging providers had earlier detection of recurrence. Future analyses in a larger population are warranted to elucidate the risks versus benefits of surveillance imaging.

A Review of Immune Checkpoint Blockade Therapy in Endometrial Cancer.

Approximately 30% of primary endometrial cancers are microsatellite instability high/hypermutated (MSI-H), and 13% to 30% of recurrent endometrial cancers are MSI-H or mismatch repair deficient (dMMR). Given the presence of immune dysregulation in endometrial cancer as described, immune checkpoint blockade (ICB) has been explored as a therapeutic mechanism, both as monotherapy and in combination with cytotoxic chemotherapy, other immunotherapy, or targeted agents. In MSI-H or dMMR advanced endometrial cancers, PD-1 inhibitors dostarlimab and pembrolizumab have shown response rates of 49% and 57%, respectively, whereas PD-L1 inhibitors avelumab and durvalumab have shown response rates of 27% and 43%, respectively. In microsatellite stable (MSS) or PD-L1-positive advanced endometrial cancers, modest activity of PD-1 inhibitors nivolumab and dostarlimab and PD-L1 inhibitors atezolizumab, avelumab, and durvalumab has been seen, with response rates ranging from 3% to 23%. Based on substantial activity in a phase Ib/II study, the U.S. Food and Drug Administration (FDA) granted lenvatinib and pembrolizumab combination therapy accelerated approval in 2019 for the treatment of advanced endometrial cancer that is not MSI-H or dMMR and has progressed following prior therapy. Although these developments have been highly impactful, a more robust understanding of the molecular and immunologic drivers of response and resistance will be critical to optimally design next-generation studies in endometrial cancer.

Racial disparities in chemotherapy administration for early-stage breast cancer: a systematic review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis to measure the extent to which race is associated with delayed initiation or receipt of inadequate chemotherapy among women with early-stage breast cancer. METHODS: We performed a systematic search of all articles published from January 1987 until June 2017 within four databases: PubMed/Medline, EMBASE, CINAHL, and Cochrane CENTRAL. Eligible studies were US-based and examined the influence of race on chemotherapy delays, cessation, or dose reductions among women with stage I, II, or III breast cancer. Data were pooled using a random effects model. RESULTS: A total of twelve studies were included in the quantitative analysis. Blacks were significantly more likely than whites to have delays to initiation of adjuvant therapy of 90 days or more (OR 1.41, 95% CI 1.06-1.87; X² = 31.05, p < 0.00001; I² = 90%). There was no significant association between race and chemotherapy dosing. Due to overlap between studies assessing the relationship between race and completion of chemotherapy, we conducted two separate analyses. Black patients were significantly more likely to discontinue chemotherapy, however, this was no longer statistically significant when larger numbers of patients with more advanced (stage III) breast cancer were included. CONCLUSIONS: These results suggest that black breast cancer patients experience clinically relevant delays in the initiation of adjuvant chemotherapy more often than white patients, which may in part explain the increased mortality observed among black patients.

New therapies for advanced, recurrent, and metastatic endometrial cancers.

Endometrial cancer is the most common gynecologic malignancy in the United States, accounting for 6% of cancers in women. In 2017, an estimated 61,380 women were diagnosed with endometrial cancer, and approximately 11,000 died from this disease. From 1987 to 2008, there was a 50% increase in the incidence of endometrial cancer, with an approximate 300% increase in the number of associated deaths. Although there are many chemotherapeutic and targeted therapy agents approved for ovarian, fallopian tube and primary peritoneal cancers, since the 1971 approval of megestrol acetate for the palliative treatment of advanced endometrial cancer, only pembrolizumab has been Food and Drug Administration (FDA)-approved for high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR) endometrial cancer; this highlights the need for new therapies to treat advanced, recurrent, metastatic endometrial cancer. In this review, we discuss current and emerging treatment options for endometrial cancer, including chemotherapy, targeted therapy, and immunotherapy. The National Cancer Institute (NCI) and others are now focusing their efforts on the design of scientifically rational targeted therapy and immunotherapy trials for specific molecular phenotypes of endometrial cancer. This is essential for the advancement of cancer care for women, which is threatened by a severe enrollment decline of approximately 80% for gynecologic oncology clinical trials.