Abstract: Immune-checkpoint inhibitors have become valuable therapies in the treatment of patients with non-small-cell lung cancer (NSCLC). Recent clinical trials have shown promising results with regard to efficacy and toxicity profiles of these agents compared to cytotoxic chemotherapy. Nivolumab was one of the first immune-checkpoint inhibitors to demonstrate clinical activity in patients with NSCLC, and is currently approved in the US for treatment of patients with advanced squamous and nonsquamous NSCLC who have progressed on or after platinum-based chemotherapy. This review provides an update on nivolumab’s pharmacology, safety, and efficacy, as established by the CheckMate trials. We also discuss specific applications and strategies for the use of nivolumab in NSCLC patients, as well as predictive biomarkers and their role in treatment selection. Keywords: nivolumab, non-small-cell lung cancer, immune-checkpoint inhibitor, PD1
Background Natural language processing (NLP) offers significantly faster variable extraction compared to traditional human extraction but cannot interpret complicated notes as well as humans can. Thus, we hypothesized that an “NLP-assisted” extraction system, which uses humans for complicated notes and NLP for uncomplicated notes, could produce faster extraction without compromising accuracy. Objective The aim of this study was to develop and pilot an NLP-assisted extraction system to leverage the strengths of both human and NLP extraction of prostate cancer Gleason scores. Methods We collected all available clinical and pathology notes for prostate cancer patients in an unselected academic biobank cohort. We developed an NLP system to extract prostate cancer Gleason scores from both clinical and pathology notes. Next, we designed and implemented the NLP-assisted extraction system algorithm to categorize notes into “uncomplicated” and “complicated” notes. Uncomplicated notes were assigned to NLP extraction and complicated notes were assigned to human extraction. We randomly reviewed 200 patients to assess the accuracy and speed of our NLP-assisted extraction system and compared it to NLP extraction alone and human extraction alone. Results Of the 2051 patients in our cohort, the NLP system extracted a prostate surgery Gleason score from 1147 (55.92%) patients and a prostate biopsy Gleason score from 1624 (79.18%) patients. Our NLP-assisted extraction system had an overall accuracy rate of 98.7%, which was similar to the accuracy of human extraction alone (97.5%; P=.17) and significantly higher than the accuracy of NLP extraction alone (95.3%; P<.001). Moreover, our NLP-assisted extraction system reduced the workload of human extractors by approximately 95%, resulting in an average extraction time of 12.7 seconds per patient (vs 256.1 seconds per patient for human extraction alone). Conclusions We demonstrated that an NLP-assisted extraction system was able to achieve much faster Gleason score extraction compared to traditional human extraction without sacrificing accuracy.
108 Background: Early implementation of palliative care has shown to improve quality of life and prolong survival in pts with metastatic NSCLC. We sought to investigate the attitudes and referral practices among medical oncologists treating pts with metastatic NSCLC. Methods: Participants were identified through the IASLC 2015 membership directory. All participants were contacted via email to complete an 18-question online survey that included demographic variables as well as questions on referral practice and attitudes regarding the role of palliative care in the treatment of metastatic NSCLC pts. Results: The response rate was 31% (93/303). The majority of participants (94%) practice in an academic setting and 57% had no prior palliative care training. 88% of oncologists report easy access to palliative care providers and 94% have an affiliated palliative care practice within their institution. 83% believe there is definitive evidence in the literature supporting the benefit of early palliative care; however, 40% feel this evidence supports only improved quality of life, not prolonged survival. 58% of oncologists agree that metastatic NSCLC pts should be referred to palliative care early in their disease course. In practice, however, they refer 19% of pts to palliative care at the time of first treatment initiation and this only increases to 38% when considering all referrals made when pts are actively receiving chemotherapy. Reasons for not referring pts include lack of symptoms (56%), belief that oncologists can manage palliative care needs independently (46%), not wanting to burden pts with appointments (41%), concern that referral may not be well received by pts (38%), and long wait times (20%). Reasons for referral include inadequately managed pain (97%), no further treatment options (70%), weak support network (71%), depression/anxiety (68%), other cancer-related symptoms (69%), dwindling treatment options (66%), and lack of time to address palliative care needs (58%). Conclusions: While most oncologists acknowledge the benefit of early palliative care consultation for metastatic NSCLC pts, a minority of pts are referred and strategies to improve referrals are needed.
Novel agents targeting immune checkpoint molecules or mutated BRAF are active therapeutic options for patients with BRAF V600 -mutant melanoma. However, the most effective first-line treatment and the optimal sequencing of these agents have not been well characterized. To explore this, we retrospectively assessed 114 patients from 4 centers with advanced, BRAF V600 -mutant melanoma who received anti-programmed cell death-1 (PD-1)/PD-L1 antibodies. We evaluated clinical outcomes, including objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) to initial and subsequent therapies in patients that received anti-PD-1 first (n=56) versus those that received BRAF±MEK inhibitors (BRAFi) first (n=58). Median OS was similar between these groups (27.5 vs. 40.3 mo, P =0.71). Patients who progressed on anti-PD-1 during the study timeframe had worse outcomes after starting subsequent BRAFi than those who had not received prior anti-PD-1 (median PFS 5 vs. 7.4 mo, median OS 10.6 vs. 40.3 mo). Similarly, patients who previously progressed on BRAFi had seemingly inferior outcomes after starting anti-PD-1 compared with those without prior BRAFi, including ORR (25% vs. 41%), median PFS (2.8 vs. 10.6 mo) and median OS (8.2 vs. 27.6 mo). Notably, patients who benefited >6 months from BRAFi had superior ORR to subsequent anti-PD-1 compared with those with more rapid progression (<6 mo) on BRAFi (34% vs. 15%, P =0.04). We conclude that either BRAFi or anti-PD-1 may be effective regardless of treatment sequence in patients with BRAF V600 -mutant melanoma, but clinical outcomes to front-line therapy are superior. In addition, we suggest a shared “responder phenotype” between BRAFi and anti-PD-1.
e16003 Background: There are limited data comparing first-line (1L) C versus IO in cisplatin-ineligible mUC patients. The primary evidence guiding treatment decisions was a May 2018 Food and Drug Administration (FDA) safety alert based on early review of two ongoing phase III trials, reporting shorter survival in PD-L1 negative patients receiving IO relative to chemotherapy. Final results from these trials are unknown and may not be applicable to a real-world cohort. Methods: We conducted a retrospective cohort study of mUC patients receiving 1L C or IO from January 1, 2011 to May 18, 2018 using the Flatiron Health electronic health record-derived database. The primary outcome was overall survival (OS) from start of 1L treatment to date of death. We compared 12- and 36-month OS, and hazard ratios before and after 12 months. Propensity score-based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier (KM) and Cox multivariable regression model estimates of comparative-effectiveness. Results: Of 2,243 patients, 562 received IO and 1,681 received C. Baseline characteristics were balanced between groups, with few exceptions (Table). In the first 12 months, IO was associated with an increased hazard of death compared to C (HR 1.38, 95% CI 1.16-1.66). Among patients who survived one year, survival was improved with IO compared to C (HR 0.50, 95% CI 0.27-0.92). Conclusions: In routine clinical practice, 1L IO was associated with inferior 12-month OS relative to C, but superior OS beyond 12 months. Clinicians and patients should carefully consider how to balance the early benefit of C against the late benefit of IO. Currently pending trial results will contribute additional evidence to inform treatment decision making. [Table: see text]
Immunotherapy has dramatically improved the prognosis for patients with melanoma and has become the cornerstone of treatment for those with advanced disease. The role of immunotherapy continues to expand with multiple new agents approved in the adjuvant as well as metastatic setting, as first-line therapy and beyond. We review the currently approved drugs for the treatment of melanoma, along with clinical trial data, adverse side effects, response assessment and future directions.
