Because of socioeconomic factors, many patients with advanced non-small cell lung cancer (NSCLC) do not receive immunotherapy in the first-line setting. It is unknown if the combination of immunotherapy with chemotherapy can provide clinical benefits in immunotherapy-naive patients with disease progression after treatment with platinum-based chemotherapy.OBJECTIVE To evaluate the safety and efficacy of the combination of pembrolizumab plus docetaxel in patients with previously treated advanced NSCLC following platinum-based chemotherapy regardless of EGFR variants or programmed cell death ligand 1 status. DESIGN, SETTING, AND PARTICIPANTSThe Pembrolizumab Plus Docetaxel for Advanced Non-Small Cell Lung Cancer (PROLUNG) trial randomized 78 patients with histologically confirmed advanced NSCLC in a 1:1 ratio to receive either pembrolizumab plus docetaxel or docetaxel alone from December 2016 through May 2019. INTERVENTIONSThe experimental arm received docetaxel on day 1 (75 mg/m 2 ) plus pembrolizumab on day 8 (200 mg) every 3 weeks for up to 6 cycles followed by pembrolizumab maintenance until progression or unacceptable toxic effects. The control arm received docetaxel monotherapy. MAIN OUTCOMES AND MEASURESThe primary end point was overall response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival, and safety. RESULTS Among 78 recruited patients, 32 (41%) were men, 34 (44%) were never smokers, and 25 (32%) had an EGFR/ALK alteration. Forty patients were allocated to receive pembrolizumab plus docetaxel, and 38 were allocated to receive docetaxel. A statistically significant difference in ORR, assessed by an independent reviewer, was found in patients receiving pembrolizumab plus docetaxel vs patients receiving docetaxel (42.5% vs 15.8%; odds ratio, 3.94; 95% CI, 1.34-11.54; P = .01). Patients without EGFR variations had a considerable difference in ORR of 35.7% vs 12.0% (P = .06), whereas patients with EGFR variations had an ORR of 58.3% vs 23.1% (P = .14). Overall, PFS was longer in patients who received pembrolizumab plus docetaxel (9.5 months; 95% CI, 4.2-not reached) than in patients who received docetaxel (3.9 months; 95% CI, 3.2-5.7) (hazard ratio, 0.24; 95% CI, 0.13-0.46; P < .001). For patients without variations, PFS was 9.5 months (95% CI, 3.9-not reached) vs 4.1 months (95% CI, 3.5-5.3) (P < .001), whereas in patients with EGFR variations, PFS was 6.8 months (95% CI, 6.2-not reached) vs 3.5 months (95% CI, 2.3-6.2) (P = .04). In terms of safety, 23% (9 of 40) vs 5% (2 of 38) of patients experienced grade 1 to 2 pneumonitis in the pembrolizumab plus docetaxel and docetaxel arms, respectively (P = .03), while 28% (11 of 40) vs 3% (1 of 38) experienced any-grade hypothyroidism (P = .002). No new safety signals were identified. CONCLUSIONS AND RELEVANCEIn this phase 2 study, the combination of pembrolizumab plus docetaxel was well tolerated and substantially improved ORR and PFS in patients with advanced NSCLC who had previous progression after platinum-based chem...

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CYP2D6 activity derive inferior therapeutic benefit from tamoxifen, and may alternatively be treated with newer aromatase inhibitors (AIs). However, the high costs of AIs provide incentive for identifying patients who will benefit from tamoxifen prior to treatment. We estimated the cost-effectiveness of genetic testing in combination with hormone therapy for early breast cancer in Canada. METHODS: We performed a cost-effectiveness analysis using a Markov model from a societal perspective and a lifetime horizon. The base case assumed 40-year-old ERϩ hormone sensitive women with early breast cancer. We evaluated: genetic testing with subsequent treatment based on genetic status (tamoxifen for CYP2D6 extensive metabolizers and AIs for decreased metabolizers) vs. no testing (tamoxifen for all patients). Probabilistic sensitivity analysis was used to incorporate parameter uncertainties. Expected value of perfect information was performed to identify future research directions. Outcomes were quality-adjusted life years (QALYs) and costs. RESULTS: The genetic testing and treatment combination strategy resulted in a 2.87 QALY gain when compared to no testing. The incremental cost was CAD $25,661 compared to standard care, and the incremental cost-effectiveness ratio (ICER) for the base case was $8,927 per QALY. The ICER was sensitive to disease progression among intermediate metabolizers, and costs of terminal care and aromatase inhibitors. CONCLUSIONS: CYP2D6 Genetic testing in combination with hormone treatment for early breast cancer patients may be economically attractive in the current setting. Future research is required to determine efficacy of extended tamoxifen (more than 5 years) treatment, the rate of progression to a more advanced cancer health state and adverse events by CYP2D6 polymorphism. OBJECTIVES:To develop a cost-effectiveness analysis of LC versus TC in the treatment of metastatic breast cancer ErBb2ϩ after progression to one regime of trastuzumab. METHODS: A Markov model was designed with one week length cycles, two years time horizon and two stages: Free of Progression and Progression. The analysis was conducted from the perspective of the Mexican public Health System for patients who had progressed to the first scheme of trastuzumab (around 900 patients). Efficacy data for this specific population was based on and ad-hoc sub analysis reported by Cameron 2010 for LC: 0.50, pϭ0.001 and per protocol population reported by Minckwitz 2009 for TC: 0.69, pϭ0.034. Baseline analysis used time to progression for monotherapy reported by Minckwitz and an univariate sensitivity analysis was run with monotherapy results by Cameron. Government prices were used for capecitabine (2000 mg/m2/day), lapatinib (1250 mg/day) and trastuzumab (2 mg/kg/week). One chemotherapy session cost was added every three weeks in the trastuzumab arm. Results are reported in US dollars. RESULTS: Cost-effectiveness ratio for LC and TC was $650.82 and $756.86 respectively. LC group had an average incremental effectiveness of 7.47 weeks...

Conclusion: Pembrolizumab monotherapy improved OS with a favorable safety profile vs platinum-based chemotherapy as first-line therapy in Chinese patients with locally advanced/metastatic NSCLC without sensitizing EGFR/ALK aberrations and a PD-L1 TPS 1%. Findings are consistent with the global study primary endpoints, supporting first-line use of pembrolizumab for PD-L1eexpressing advanced/metastatic NSCLC in China.