A Phase 2 Study of Docetaxel, Ramucirumab, and Pembrolizumab for Patients With Metastatic or Recurrent Non-Small-Cell Lung Cancer (NSCLC) who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade.

BACKGROUND: There is an urgent and unmet need for more effective treatment options for patients with metastatic and recurrent non-small-cell lung cancer (NSCLC) who progressed on platinum-based therapy, immune checkpoint inhibitors (ICI), and targeted therapies. Currently, the combination of docetaxel (D) and ramucirumab (R) is the next best salvage therapy with a modest historical progression free survival (PFS) of 4.5 months and 6-month PFS rate of 37% predating the era of ICI use. Anecdotal reports in patients who progressed on ICI suggest a higher response rate to docetaxel compared to historical experience. Furthermore, tumor related angiogenesis promotes tumor growth and may contribute to immune escape in patients treated with ICI. Therapeutic combination with anti-angiogenic, ICI, and chemotherapy have independently demonstrated clinical efficacy without additive toxicities in NSCLC patients. PATIENTS AND METHODS: This multicenter, single arm, open label, phase 2 study will evaluate the safety and preliminary efficacy of the combination of docetaxel 75 mg/m2, ramucirumab 10 mg/kg, and pembrolizumab 200 mg in up to 41 patients with metastatic or recurrent NSCLC after progression on concomitant or sequential platinum-based chemotherapy and ICI. This treatment will be given intravenously on the same day every 3 weeks until disease progression, occurrence of severe side effects, or no clinical benefit. The primary endpoint is 6-month PFS rate. CONCLUSIONS: This is the first study to evaluate the safety and efficacy of ICI combined with docetaxel and ramucirumab. The findings could provide valuable information for developing new treatment strategies for NSCLC patients.

RET Fusion: Joining the Ranks of Targetable Molecular Drivers in NSCLC.

The era of precision medicine has resulted in the identification of a number of genomic alterations that can be targeted with novel therapies. In lung adenocarcinomas, a histology structure that accounts for nearly 50% of all cases of lung cancer, and a number of genomic targets have been linked with effective targeted therapies. For patients with advanced-stage lung adenocarcinomas, molecular testing is now a standard part of diagnostic workup; for patients that have specific driver molecular events, targeted therapies have resulted in substantial improvement in efficacy without excessive toxicity. RET gene fusions are present in approximately 1% to 2% of NSCLC. It is emerging as a new targetable driver for this population. Despite sensitivity to platinum-based chemotherapy and conflicting small reports regarding the efficacy of immune checkpoint inhibitors, there have been limited treatment approaches for this subset of patients. Multiple nonselective RET tyrosine kinase inhibitors exhibited modest anti-RET activity with an increased off-target toxicity profile that often required dose interruption, reduction, or treatment cessation. Recently, novel selective RET inhibitors pralsetinib (BLU-667) and selpercatinib (LOXO-292) have exhibited promising clinical activity with low adverse effect profile in early clinical trials. These new agents are poised to represent a new hope for this special subgroup with unmet needs.

Interval between first palliative care consult and death in patients diagnosed with advanced cancer at a comprehensive cancer center.

PURPOSE: Most referrals to palliative care and hospice occur late in the trajectory of the disease although an earlier intervention could decrease patients' symptom distress. The purpose of this study was to determine the interval between first palliative care consult (PC1) and death (D) in patients diagnosed with advanced cancer (aCA) at our comprehensive cancer center and if such interval has increased over time. METHODS: The study group was 2868 consecutive patients who had their PC1 during a 30-month period. We reviewed the charts for information about demographics, cancer type, date of cancer (CA) diagnosis, aCA diagnosis, PC1, and D. aCA was defined as locally recurrent or metastatic. RESULTS: One thousand four hundred four patients (49%) were female, 1791 (62%) were less than 65 years old, 2563 (89%) had solid tumors, and 2004 (70%) were white. The median PC1-D, aCA-PC1, aCA-D, and CA-D intervals were 42, 147, 250, and 570 days, respectively. The median PC1-D interval was longer in patients with solid tumors (p < 0.0001), less than 65 years old (p = 0.002), and females (p = 0.004). PC1-D was not affected by ethnicity (p = 0.42). The median PC1-D interval in 5 consecutive half-years was 46, 56, 42, 41, and 34 days, respectively (p = 0.02). The number of PC1 in this period increased from 544 to 654 (20%). The ratio of PC involvement in the aCA-D period (PC1-D/aCA-D) decreased from 0.30 to 0.26 over the 5 half-year periods (p = 0.0004). CONCLUSIONS: The first palliative care consultation to death interval has decreased over time at our center. Education is needed among our referring physicians for earlier access to palliative care. Prospective studies are needed to establish the appropriate timing of the first palliative care consultation.