Inclusion of Racial and Ethnic Minorities in Cancer Clinical Trials: 30 Years After the NIH Revitalization Act, Where Are We?

The lack of diversity in cancer trials is a multifaceted, decades-old problem that has remained persistent despite efforts to increase the number of participants from underrepresented racial and ethnic backgrounds. This lack of meaningful improvement is a problem that continues to perpetuate inequities in cancer care. For optimal generalizability of clinical trial results, populations that are likely to be treated must be adequately represented. Beyond consensus statements, policy enactments, and federal mandates, strategic collaboration with at-risk underrepresented communities is critically necessary to improve the accrual of minorities to cancer clinical trials. As such, the clarion call is for advanced practitioners in oncology to take a keen interest in this issue and seek to develop population-specific strategies to bridge and eliminate the disparity gap and improve outcomes in these groups.

Pembrolizumab After Completion of Locally Ablative Therapy for Oligometastatic Non-Small Cell Lung Cancer: A Phase 2 Trial.

IMPORTANCE: Patients with oligometastatic non-small cell lung cancer (NSCLC) may benefit from locally ablative therapy (LAT) such as surgery or stereotactic radiotherapy. Prior studies were conducted before the advent of immunotherapy, and a strong biological rationale for the use of immunotherapy exists in a minimal residual disease state. OBJECTIVE: To evaluate whether the addition of pembrolizumab after LAT improves outcomes for patients with oligometastatic NSCLC. DESIGN, SETTING, AND PARTICIPANTS: This single-arm phase 2 trial of pembrolizumab therapy was performed from February 1, 2015, through September 30, 2017, at an academic referral cancer center. The 51 eligible patients enrolled had oligometastatic NSCLC (≤4 metastatic sites) and had completed LAT to all known sites of disease. Data were analyzed from February 1, 2015, to August 23, 2018. INTERVENTIONS: Within 4 to 12 weeks of completing LAT, patients began intravenous pembrolizumab therapy, 200 mg every 21 days, for 8 cycles, with provision to continue to 16 cycles in the absence of progressive disease or untoward toxic effects. MAIN OUTCOMES AND MEASURES: The 2 primary efficacy end points were progression-free survival (PFS) from the start of LAT (PFS-L), which preceded enrollment in the trial, and PFS from the start of pembrolizumab therapy (PFS-P). The study was powered for comparison with historical data on the first efficacy end point. Secondary outcomes included overall survival, safety, and quality of life as measured by the Functional Assessment of Cancer Therapy-Lung instrument. RESULTS: Of 51 patients enrolled, 45 (24 men [53%]; median age, 64 years [range, 46-82 years]) received pembrolizumab. At the time of analysis, 24 patients had progressive disease or had died. Median PFS-L was 19.1 months (95% CI, 9.4-28.7 months), significantly greater than the historical median of 6.6 months (P = .005). Median PFS-P was 18.7 months (95% CI, 10.1-27.1 months). Eleven patients died. Overall mean (SE) survival rate at 12 months was 90.9% (4.3%); at 24 months, 77.5% (6.7%). Neither programmed death ligand 1 expression nor CD8 T-cell tumor infiltration was associated with PFS-L. Pembrolizumab after LAT yielded no new safety signals and no reduction in quality of life. CONCLUSIONS AND RELEVANCE: Pembrolizumab after LAT for oligometastatic NSCLC appears to improve PFS with no reduction in quality of life. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02316002.

Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer.

OBJECTIVES: Efficient use of nivolumab in non-small-cell lung cancer (NSCLC) has been limited by the lack of a definitive predictive biomarker. In patients with metastatic melanoma treated with ipilimumab, a pretreatment neutrophil-to-lymphocyte ratio (NLR)<5 has been associated with improved survival. This retrospective cohort study aimed to determine whether the pretreatment NLR was associated with outcomes in NSCLC patients treated with nivolumab. METHODS: We reviewed the medical records of all patients with previously treated advanced NSCLC who received nivolumab between March 2015 and March 2016 outside of a clinical trial at the University of Pennsylvania. Patients were dichotomized according to pretreatment NLR<5 vs. ≥5. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment NLR on overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). RESULTS: 175 patients were treated. Median age was 68 (range, 33-88); 54% were female. Twenty-five percent of patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2; 46% had received ≥2 prior systemic therapies. In multivariate analyses, pretreatment neutrophil-to-lymphocyte ratio (NLR) ≥5 was independently associated with inferior OS (median 5.5 vs. 8.4 months; HR 2.07, 95% CI 1.3-3.3; p=0.002) and inferior PFS (median 1.9 vs. 2.8 months; HR 1.43, 95% CI 1.02-2.0; p=0.04). CONCLUSIONS: In a cohort of patients with NSCLC treated with nivolumab in routine practice, pretreatment NLR≥5 was associated with inferior outcomes. It is unclear whether this marker is predictive or prognostic. Prospective studies are warranted to determine the utility of NLR in the context of other biomarkers of programmed death-1 (PD-1) therapy.

Induction chemotherapy with cetuximab, carboplatin and paclitaxel for the treatment of locally advanced squamous cell carcinoma of the head and neck.

Although controversy exists in the management of locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), clinicians often use induction chemotherapy for treatment of the most advanced cases. One promising regimen combines weekly cetuximab (400 mg/m2 loading dose followed by 250 mg/m2) with carboplatin (AUC of 2) and paclitaxel (90 mg/m2). We retrospectively evaluated patients treated with this regimen prior to definitive chemoradiation or surgery between May 2008 and December 2011. The primary endpoint used for this retrospective analysis was feasibility. Thirty consecutive, unselected patients were included. Median follow-up was 13.7 months (range, 5.0-38.7 months). All but one patient had stage IV SCCHN. Dose intensity was high for carboplatin (92%), paclitaxel (93%) and cetuximab (85%). Grade 3-4 toxicities occurred in <7% of the study population and were limited to rash, neutropenia and infusion reactions. Response rate (RR) to induction chemotherapy was 97% (30% complete response, 67% partial response). All patients completed subsequent chemoradiotherapy or surgery. Nineteen patients (63%) demonstrated a complete response and 11 patients (37%) demonstrated a partial response. Median overall survival and progression-free survival data are not yet mature. The RR to therapy in our off-protocol experience is at least comparable to that observed in the two phase II studies of this regimen and appears superior to that observed with docetaxel, cisplatin and fluorouracil (TPF).

Proton and phosphorous MR spectroscopy in squamous cell carcinomas of the head and neck.

RATIONALE AND OBJECTIVES: Phosphorous magnetic resonance spectroscopy ((31)P MRS) has been used to evaluate and predict treatment response in squamous cell carcinoma of the head and neck (HNSCC). Several studies have also shown the potential of proton MRS ((1)H MRS) in assessing response in HNSCC. In view of the inherent limitations associated with performing (31)P MRS in clinical settings, the current study was performed to explore whether (1)H MRS could provide similar or complementary metabolic information in HNSCC. MATERIALS AND METHODS: Fifteen patients with HNSCC underwent pretreatment magnetic resonance imaging. Both (1)H MRS and (31)P MRS were performed on viable solid parts of the metastatic lymph nodes of these patients. Peak areas of total choline (tCho) and unsuppressed water as observed on (1)H MRS and phosphomonoester (PME) and beta-nucleotide triphosphate (beta-NTP) on (31)P MRS were computed. Pearson's correlation coefficient was used to correlate the tCho/water and PME/beta-NTP ratios. RESULTS: In all patients, the metastatic nodes appeared hyperintense on T2-weighted images and hypointense on T1-weighted images with variable signal intensity. A prominent resonance of tCho on (1)H MRS and a resonance of PME on (31)P MRS from the metastatic nodes of all patients were observed. A moderate correlation of 0.31 was observed between tCho/water and PME/beta-NTP (P > .05). CONCLUSIONS: The biochemical pathways involved in (1)H MRS of tCho may be different from the phospholipid metabolites seen on (31)P MRS of head and neck cancers, and thus the two MRS techniques may be complementary to each other.

Effects of caregiving demand, mutuality, and preparedness on family caregiver outcomes during cancer treatment.

PURPOSE/OBJECTIVES: To test a model of family caregiving derived from the interactionist approach to role theory that hypothesized that three caregiving role implementation variables (caregiving demand, mutuality between caregivers and patients, and preparedness for caregiving) would predict multiple caregiving-specific and generic outcomes with different patterns of association across outcomes. DESIGN: Descriptive, correlational. SETTING: Surgical, radiation, and medical oncology settings. SAMPLE: 87 family caregivers of adults receiving treatment for solid tumors or lymphoma. METHODS: Caregivers completed the Demand and Difficulty subscales of the Caregiving Burden Scale; the Mutuality, Preparedness, and Global Strain scales of the Family Care Inventory; and the 30-item short form of the Profile of Mood States. Data were analyzed with simultaneous multiple regression. MAIN RESEARCH VARIABLES: Caregiving demand, mutuality, preparedness, caregiving difficulty, global caregiver strain, tension, depression, anger, fatigue, vigor, confusion, and total mood disturbance. FINDINGS: The model explained statistically significant proportions of variance in each outcome, with different patterns of association across outcomes. Demand was associated most strongly with caregiving difficulty and global strain. Mutuality was associated most strongly with caregiver anger. Unexpectedly, preparedness was associated more strongly with mood disturbance outcomes than with the caregiving-specific variables of difficulty and strain. CONCLUSIONS: Further research should explore models that address implementation of the caregiving role to better elucidate how family caregivers learn and carry out the important role. IMPLICATIONS FOR NURSING: Clinical assessment should include caregiving demand, the quality of the relationship between caregiver and patient, and preparedness for caregiving. Interventions could be tailored to meet caregiver needs in each area.