BACKGROUNDFirst-line chemotherapy for advanced esophageal squamous-cell carcinoma results in poor outcomes. The monoclonal antibody nivolumab has shown an overall survival benefit over chemotherapy in previously treated patients with advanced esophageal squamous-cell carcinoma. METHODSIn this open-label, phase 3 trial, we randomly assigned adults with previously untreated, unresectable advanced, recurrent, or metastatic esophageal squamouscell carcinoma in a 1:1:1 ratio to receive nivolumab plus chemotherapy, nivolumab plus the monoclonal antibody ipilimumab, or chemotherapy. The primary end points were overall survival and progression-free survival, as determined by blinded independent central review. Hierarchical testing was performed first in patients with tumor-cell programmed death ligand 1 (PD-L1) expression of 1% or greater and then in the overall population (all randomly assigned patients). RESULTSA total of 970 patients underwent randomization. At a 13-month minimum followup, overall survival was significantly longer with nivolumab plus chemotherapy than with chemotherapy alone, both among patients with tumor-cell PD-L1 expression of 1% or greater (median, 15.4 vs. 9.1 months; hazard ratio, 0.54; 99.5% confidence interval [CI], 0.37 to 0.80; P<0.001) and in the overall population (median, 13.2 vs. 10.7 months; hazard ratio, 0.74; 99.1% CI, 0.58 to 0.96; P = 0.002). Overall survival was also significantly longer with nivolumab plus ipilimumab than with chemotherapy among patients with tumor-cell PD-L1 expression of 1% or greater (median, 13.7 vs. 9.1 months; hazard ratio, 0.64; 98.6% CI, 0.46 to 0.90; P = 0.001) and in the overall population (median, 12.7 vs. 10.7 months; hazard ratio, 0.78; 98.2% CI, 0.62 to 0.98; P = 0.01). Among patients with tumor-cell PD-L1 expression of 1% or greater, a significant progression-free survival benefit was also seen with nivolumab plus chemotherapy over chemotherapy alone (hazard ratio for disease progression or death, 0.65; 98.5% CI, 0.46 to 0.92; P = 0.002) but not with nivolumab plus ipilimumab as compared with chemotherapy. The incidence of treatment-related adverse events of grade 3 or 4 was 47% with nivolumab plus chemotherapy, 32% with nivolumab plus ipilimumab, and 36% with chemotherapy alone. CONCLUSIONSBoth first-line treatment with nivolumab plus chemotherapy and first-line treatment with nivolumab plus ipilimumab resulted in significantly longer overall survival than chemotherapy alone in patients with advanced esophageal squamous-cell carcinoma, with no new safety signals identified. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 648 ClinicalTrials.gov number, NCT03143153.

Background The study was conducted to estimate the relative cost effectiveness of contraceptives in the United States from a payer’s perspective. Methods A Markov model was constructed to simulate costs for 16 contraceptive methods and no method over a 5-year period. Failure rates, adverse event rates, and resource utilization were derived from the literature. Sensitivity analyses were performed on costs and failure rates. Results Any contraceptive method is superior to “no method”. The three least expensive methods were the copper-T IUD ($647), vasectomy ($713) and LNG-20 IUS ($930). Results were sensitive to the cost of contraceptive methods, the cost of an unintended pregnancy, and plan disenrollment rates. Conclusion The copper-T IUD, vasectomy, and the LNG-20 IUS are the most cost-effective contraceptive methods available in the United States. Differences in method costs, the cost of an unintended pregnancy, and time horizon are influential factors that determine the overall value of a contraceptive method.

PURPOSE Nivolumab received US Food and Drug Administration approval as a single agent or in combination with ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on CheckMate 142. Presented are results of nivolumab plus low-dose ipilimumab in the first-line therapy cohort from the phase II CheckMate 142 study. PATIENTS AND METHODS Patients with no prior treatment in the metastatic setting for MSI-H/dMMR CRC were treated with nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks until disease progression. The primary end point was objective response rate (investigator assessment; RECIST v1.1). RESULTS Median age of treated patients was 66 years (N = 45). Median follow-up was 29.0 months. Objective response rate and disease control rate were 69% (95% CI, 53 to 82) and 84% (95% CI, 70.5 to 93.5), respectively, with 13% complete response rate. Median duration of response was not reached; 74% of responders had ongoing responses at data cutoff. Median progression-free survival and median overall survival were not reached with minimum follow-up of 24.2 months (24-month rates, 74% and 79%, respectively). Clinical benefit was observed regardless of baseline demographic and tumor characteristics, including BRAF or KRAS mutation status. In a post hoc analysis, of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 remained progression-free. Patient-reported outcomes were stable over the treatment period. Grade 3-4 treatment-related adverse events occurred in 22% of patients; 13% discontinued because of any-grade treatment-related adverse events. CONCLUSION Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated as a first-line treatment for MSI-H/dMMR mCRC. Based on these promising data, randomized studies are warranted.

Introduction: Currently available second-line (2L) therapies for advanced/metastatic esophageal squamous cell carcinoma (adv/met ESCC) include the taxanes paclitaxel and docetaxel. In clinical trials, such therapies have provided only modest improvements in survival. Few studies have assessed outcomes in routine clinical practice in the USA. We compared realworld clinical outcomes in the US for patients receiving taxane or non-taxane 2L therapy for adv/met ESCC. Methods: The Flatiron Health database was used to identify patients diagnosed with adv/ met ESCC (1 January 2011-31 January 2019) who received 2L therapy; index date was date of adv/met diagnosis. Baseline variables and treatment regimens received were identified. Overall survival (OS; 2L start until death or last recorded medical activity) and duration of therapy (DoT; start of 2L therapy until last administration date of 2L therapy) in patients receiving taxane vs. non-taxane-based therapies in the 2L setting were estimated by Kaplan-Meier method. Results: There were no clear differences in baseline characteristics between patients who received 2L taxane therapy (n = 37) and 2L nontaxane therapy (n = 49). Median (95% CI) 2L OS was significantly longer with 2L taxanes (7.3 [5.9-11.5] months) vs. 2L non-taxanes (5.1 [2.9-7.6] months); median (95% CI) 2L DoT was 2.1 (1.8-3.0) months vs. 3.3 (2.6-6.7) months, respectively. Conclusion: Survival was generally poor in patients receiving 2L therapy for adv/met ESCC and was longer in patients receiving 2L taxanes than 2L non-taxane therapy. Efficacious, tolerable therapies for ESCC in the 2L setting are urgently needed.

Contraceptive use in the United States is virtually universal among women of reproductive age. However, unplanned pregnancies continue to occur and can be largely attributed to the nonuse and misuse of contraception. Reducing unintended pregnancies constitutes a critical goal for managed care and the public. This can be achieved in part with intrauterine devices (IUDs), which are an effective method of contraception that require a one-time insertion and stay in place for 5-10 years. Therefore, compliance issues are largely mitigated, and actual use efficacy is the same as perfect use efficacy. The IUD is also reversible, unlike tubal ligation, and could potentially be the contraceptive of choice in today's environment. Unfortunately, safety concerns surrounding the use of older IUDs have precluded many women from recognizing the benefits of their use. Currently, the only approved IUDs in the United States are ParaGard, the copper IUD, and Mirena, the levonorgestrel-releasing intrauterine system (LNG-IUS). These devices offer superior safety profiles compared with those products that were withdrawn from the market in the 1970s. In addition to a favorable safety and tolerability profile, the LNG-IUS offers an advantage over copper IUDs, demonstrating improved efficacy in preventing intrauterine and ectopic pregnancies. Successful communication between patients and providers regarding the improved safety and efficacy of newer IUDs will ensure an appropriate place in therapy. Thus, greater numbers of women will recognize the IUD as a safe, cost-effective means to contraception, thereby reducing the economic and social burdens associated with unplanned pregnancies.

Aim: Study first-line (1L) treatment patterns and economic outcomes among patients with advanced metastatic gastric cancer (GC) and esophageal cancer (EC). Materials & methods: Newly diagnosed patients with systemic GC and EC treatments were identified between 1 January 2011 and 31 July 2017; costs were presented as per patient per month (PPPM) basis. Results: Study included 392 GC and 436 EC patients. Most frequently used 1L regimens were: 5-fluorouracil (5-FU) + oxaliplatin (22.5%) and epirubicin + cisplatin + 5-FU (ECF)/ECF modifications (21.9%) in patients with GC; and carboplatin + paclitaxel (29.6%) and 5-FU + oxaliplatin (11.5%) in EC patients. Mean all-cause costs were US$16,242 PPPM for GC, and $18,384 PPPM for EC during 1L treatment. Conclusion: GC and EC were resource intensive and costly. High costs and short treatment durations underscored a gap in care in 1L treatment.

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262 Background: This analysis evaluated HRQoL as exploratory endpoints in CheckMate 648, a randomized, open-label, global Phase 3 study, evaluating treatment with N+I, N+CT and CT alone in inoperable advanced, recurrent, or metastatic ESCC. Methods: The effects of N+I vs N+CT vs CT on HRQoL were assessed using the Functional Assessment of Cancer Therapy-Esophageal (FACT-E) (including the GP5 item to assess impact of side effects) and EQ-5D-3L. A mixed model for repeated measures was used to evaluate longitudinal changes from baseline (BL) and differences between treatment groups. Comparison of the risk of being bothered by the side effects of treatment was estimated for the GP5 using generalized estimating equation (GEE). Time to confirmed deterioration (TTCD) was assessed using Kaplan-Meier plots along with Cox proportional hazard models. Analyses were conducted on both the all-randomized population and the subset of patients with PD-L1 expression ≥1%. Results: 970 pts were randomized 1:1:1 to N+I (n=325), N+CT (n=321), or CT (n=324). 90% of pts completed both a BL and at least one on-treatment assessment and were included in the PRO analysis population. FACT-E (all randomized pts). Study showed similar BL scores across all 3 treatment groups. Changes from BL showed a trend towards better HRQoL for pts treated with N+I and N+CT compared to CT alone, however these results were not statistically significant. Patients treated with N+I had significantly decreased risk of experiencing bother associated with the side effects of treatment than patients treated with either N+CT or CT. TTCD analysis demonstrated delayed deterioration for pts treated with N+CT vs CT. Findings for PD-L1 ≥1% subpopulation were similar to all randomized pts. Conclusions: In pts with inoperable advanced, recurrent, or metastatic ESCC, HRQoL is maintained throughout treatment with N+I and N+CT. Trends towards better HRQoL and decreased risk of deterioration were observed with N+I and N+CT compared to CT alone. Clinical trial information: NCT03143153. [Table: see text]