Metastatic Squamous Non-small Cell Lung Research Articles

Cost-effectiveness of additional serplulimab to chemotherapy in metastatic squamous non-small cell lung cancer patients.

To estimate the cost-effectiveness of adding serplulimab to chemotherapy for metastatic squamous non-small cell lung cancer (NSCLC) patients in a first-line setting from a Chinese perspective. A three-health state partitioned survival model was constructed to simulate disease development. The clinical data used in the model were derived from the ASTRUM-004 clinical trial. Only direct medical costs were included, and the utilities were derived from published literature. The quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were employed to evaluate health outcomes. Additionally, a sensitivity analysis was performed to verify the robustness of the results. Compared with chemotherapy alone, the addition of serplulimab resulted in an increase of 0.63 QALYs with an incremental cost of $5,372.73, leading to an ICER of $8,528.14 per QALY. This ICER was significantly lower than 3 times China's per capita GDP. The one-way sensitivity analysis suggested that the utility of PFS was the most sensitive factor on ICERs, followed by the price of serplulimab. The combination of serplulimab and chemotherapy has been shown to be a cost-effective initial treatment option for patients with metastatic squamous NSCLC with the commonly accepted willingness-to-pay threshold of 3 times the GDP per capita per QALY in China.

Abstract C030: HARMONi-3: A randomized, controlled, multiregional Phase 3 study of ivonescimab combined with chemotherapy versus pembrolizumab combined with chemotherapy for the first-line treatment of metastatic squamous non-small cell lung cancer

Abstract BACKGROUND In the first-line metastatic squamous non-small cell lung cancer (NSCLC) setting, treatment with the combination of a PD-1 checkpoint inhibitor plus platinum doublet chemotherapy has become standard of care1,2. The addition of antiangiogenic agents to immunotherapy has emerged as a promising strategy for cancer treatment3,4,5. Therefore, a combined anti-angiogenesis and PD-1 blockade strategy with a bispecific PD-1 and VEGF antibody may improve clinical outcomes. Ivonescimab (SMT112/AK112) is a novel tetravalent bispecific antibody (2 binding sites for PD-1 and 2 binding sites for VEGF) with an engineered Fc-null region and a half-life of 6-7 days. In the presence of VEGF, binding affinity to PD-1 increases more than 10-fold6. Given the correlation between VEGF and PD-1 expression in the tumor microenvironment6,7,8, simultaneous blockade of these 2 targets by ivonescimab drives antitumor activity9,10. Additionally, the engineered Fc-null region and shorter half-life could potentially lead to reduced adverse events​, compared to co-administration of individual anti-PD-(L)1 and anti-VEGF agents7,8,10. At ASCO 2023, Zhang L, et al. (abstract# 9087) reported Phase 2 trial data, which included 63 first-line advanced or metastatic squamous NSCLC patients without EGFR/ALK alterations treated with ivonescimab plus paclitaxel and carboplatin. These patients had an objective response rate of 67%, a median duration of response of 15 months, 9-month overall survival (OS) estimate of 93% (median OS not reached). Furthermore, ivonescimab was well tolerated in combination with platinum doublet chemotherapy with a treatment emergent adverse event discontinuation rate of 11%. TRIAL DESIGN HARMONi-3 is a randomized, blinded, controlled, multiregional Phase 3 study of ivonescimab combined with chemotherapy versus pembrolizumab combined with chemotherapy for the first-line treatment of metastatic squamous NSCLC. Approximately 400 patients will be randomized 1:1 to receive ivonescimab (dual blockade of PD-1/VEGF) or pembrolizumab plus carboplatin-paclitaxel/nab-paclitaxel (Q3W, 4 cycles, 21 days per cycle) followed by single-agent ivonescimab or pembrolizumab maintenance therapy for up to 2 years, or until progression, or unacceptable toxicity. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, objective response rate and duration of response (RECIST v1.1), as well as incidence/severity of adverse events. Key eligibility criteria include treatment naïve metastatic squamous NSCLC, ECOG PS 0 or 1 and exclusion of patients with major blood vessel invasion or encasement by cancer or intratumor cavitation. Citation Format: Jonathan Riess, Shun Lu, Jarushka Naidoo, Sara Kuruvilla, Annie Hung, Ahmed Khaled, Deborah Doroshow. HARMONi-3: A randomized, controlled, multiregional Phase 3 study of ivonescimab combined with chemotherapy versus pembrolizumab combined with chemotherapy for the first-line treatment of metastatic squamous non-small cell lung cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C030.

64O Lenvatinib plus pembrolizumab, pemetrexed, and a platinum (len + pembro + chemo) as first-line therapy for metastatic non squamous non-small cell lung cancer (NSCLC): Phase III LEAP-006 study

64O Lenvatinib plus pembrolizumab, pemetrexed, and a platinum (len + pembro + chemo) as first-line therapy for metastatic non squamous non-small cell lung cancer (NSCLC): Phase III LEAP-006 study

Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy in Squamous Non-Small-Cell Lung Cancer in China.

The five-year update data from the KEYNOTE-407 study have unveiled noteworthy improvements in survival outcomes achieved with pembrolizumab plus chemotherapy (Pembro+Chemo) compared to placebo plus chemotherapy (Placebo+Chemo) for patients with previously untreated metastatic squamous non-small cell lung cancer (NSCLC). Building upon this finding, our study sought to evaluate the cost-effectiveness of Pembro+Chemo, utilizing the latest available data, from the perspective of the Chinese health care system. A Markov model was employed to compare the quality-adjusted life-year (QALY), life-year (LY), total cost, and incremental cost-effectiveness ratio (ICER) between Pembro+Chemo and Placebo+Chemo. The clinical and safety data were derived from the five-year update date of the KEYNOTE-407 study. Sensitivity analyses were conducted to assess the uncertainty of the model, and additional subgroup analyses were performed to explore specific subpopulations. For patients with previously untreated metastatic squamous NSCLC, the utilization of Pembro+Chemo resulted in a improvement of 0.61 quality-adjusted life years (QALYs) along with a cost reduction of $17,491.52 when compared to Placebo+Chemo. Notably, across various subgroups with different tumor proportion scores (TPS), Pembro+Chemo demonstrated enhanced QALYs and lower total costs. From the perspective of the Chinese health care system, first-line Pembro+Chemo emerges as a dominant treatment option over Placebo+Chemo for the treatment of metastatic squamous NSCLC.

The Cost-Effectiveness of Sugemalimab Plus Chemotherapy as First-Line Treatment for Metastatic Squamous and Non-squamous NSCLC in China.

Sugemalimab is the first China-developed programmed death-ligand 1 inhibitor that has proved to be effective as a first-line treatment for both metastatic squamous and non-squamous non-small cell lung cancer (NSCLC) when used in combination with chemotherapy. This study compared the cost-effectiveness of sugemalimab plus chemotherapy (sugema + chemo) with placebo plus chemotherapy (placebo + chemo) among metastatic squamous and nonsquamous NSCLC, respectively. Separate Markov models were constructed to generate the cumulative healthcare costs and quality-adjusted life-years (QALYs) associated with two treatment strategies over a 20-year time horizon. Transition probabilities were estimated using survival data reported in the GEMSTONE-302 trial. Health state utilities and costs were derived from published literature, national databases, and local general hospitals. Sensitivity analyses were performed to test the robustness of our conclusions. Compared with first-line placebo + chem, sugema + chemo achieved an incremental cost-effectiveness ratio (ICER) of $57,842/QALY for patients with metastatic squamous NSCLC and achieved an ICER of $78,249/QALY for patients with metastatic non-squamous NSCLC. In our sensitivity analyses of a willingness-to-pay (WTP) threshold of $35,663 per QALY, the first-line sugema + chemo was only cost-effective for patient groups when the price of sugemalimab decreased. Sugema + chemo was not cost-effective as a first-line treatment for either metastatic squamous or metastatic nonsquamous NSCLC in Chinese patients compared with placebo + chemo. However, we found that sugema + chemo would be cost-effective in patients withmetastatic squamous and non-squamous NSCLC when sugemalimab's price was decreased by > 39.0% and 64.8%, respectively.

LUNG-IST-127: A pilot phase II study of maintenance cabozantinib plus pembrolizumab for patients with metastatic squamous non-small cell lung cancer (sqNSCLC) with disease control following induction therapy.

TPS9151 Background: First-line combination chemotherapy with pembrolizumab followed by maintenance pembrolizumab is the standard of care treatment for patients with metastatic sqNSCLC. This was established by the phase III KEYNOTE-407 trial, which demonstrated a median progression-free survival (PFS) of 6.4 months in the experimental arm. Despite these advances, there remains a need to continue to improve upon survival outcomes for these patients. Cabozantinib is a small-molecule inhibitor of multiple tyrosine kinsases including MET, VEGFRs, AXL, RET, and ROS, which are receptors involved in tumor cell-proliferation, angiogenesis, and immune cell regulation. Preclinical studies have demonstrated the ability of cabozantinib to modulate both adaptive and innate immune cells and to exhibit synergistic activity when used in combination with immune checkpoint inhibitors. We hypothesize that cabozantinib in combination with pembrolizumab in the maintenance phase of first-line treatment of metastatic sqNSCLC will prolong median PFS with a tolerable toxicity profile. Methods: LUNG-IST 127 is a pilot phase II, single-arm clinical trial of maintenance cabozantinib in combination with pembrolizumab for patients with metastatic sqNSCLC who achieved disease control following standard 1L induction therapy with chemotherapy and pembrolizumab. Thirty-six patients will be enrolled at 2 US sites to receive first-line induction therapy with carboplatin, nab-paclitaxel or paclitaxel, and pembrolizumab for four cycles. After induction therapy, those who have achieved disease control based on re-staging imaging will continue onto maintenance therapy with cabozantinib 40mg PO daily in combination with pembrolizumab 200mg IV every 3 weeks. The primary endpoint is PFS estimated by Kaplan-Meier methods with associated 95% confidence intervals. Based on an exploratory power analysis using an elevated one-sided alpha level of 0.40, we hypothesize that the proposed therapy will prolong median PFS from 6.4 to 9 months. Key secondary endpoints include overall survival (OS), overall response rate (ORR), and characterizing the safety and tolerability of cabozantinib in combination with pembrolizumab. Quality of life will also be measured with the EORTC QLQ-C30. Correlative endpoints include characterizing cfDNA from biofluids and assessing the change in circulating immune cells in different phases of treatment in association with PFS and OS. This trial would be the first to address whether there is clinical benefit in utilizing combination cabozantinib and pembrolizumab in the maintenance phase of treatment in metastatic sqNSCLC. Clinical trial information: NCT05613413 .

Cost-effectiveness of first-line versus second-line use of domestic anti-PD-1 antibody sintilimab in Chinese patients with advanced or metastatic squamous non-small cell lung cancer.

Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/L1) inhibitor is a promising therapeutic option that can be used as either a first-line or second-line treatment for driver-negative advanced or metastatic squamous non-small cell lung cancers (sqNSCLC). However, reuse of PD-1/L1 inhibitor in second-line beyond progression after the first-line is generally not recommended. Therefore, oncologists face challenges in making a proper decision of using PD-1/L1 inhibitor. This analysis aimed to determine whether it is more cost-effective to use sintilimab, a domestic anti-PD-1 drug in China, as a first-line treatment than reserving it until second-line. We conducted a cost-effectiveness analysis to compare the use of sintilimab in the first-line setting with reserving its use until the second-line for driver-negative advanced or metastatic sqNSCLC from the perspective of the Chinese healthcare system. A Markov model composed of five main mutually independent health states and three temporary health states was established to simulate patients' clinical trajectory. Transition probabilities, including disease progression, survival, and adverse events-related treatment discontinuation, were estimated using data from the ORIENT-12, ORIENT-3, and ALTER0303 clinical trials. The robustness of the model was assessed using deterministic sensitivity analysis (DSA) and probabilistic sensitivity analyses. Reserving the use of sintilimab until the second-line was associated with a greater effectiveness (1.52 vs. 1.37 quality-adjusted life-years [QALYs]) and a higher healthcare cost ($12,203 vs. $14,045) compared with the first-line sintilimab, resulting in an incremental cost-effectiveness ratio (ICER) of $12,693 per QALY. The results of DSA suggested that variations in all parameters did not result in the ICERs surpassing the willingness-to-pay threshold of $35,663/QALY. For Chinese patients with driver-negative advanced or metastatic sqNSCLC, reserving the use of sintilimab until the second-line represents a cost-effective treatment strategy compared with the first-line treatment. Thisfindingis useful to inform Chinese healthcare policymakers regarding the optimized treatment strategies of use of domestic PD-1/L1 inhibitors sintilimab.

328P Long-term follow-up of pembrolizumab plus chemotherapy in Chinese patients with metastatic squamous non-small cell lung cancer (NSCLC) from KEYNOTE-407

First-line pembrolizumab (pembro) + paclitaxel and carboplatin (chemo) improved outcomes vs placebo (pbo) + chemo in Chinese patients (pts) with metastatic squamous NSCLC enrolled in the KEYNOTE-407 global and China extension studies, consistent with the global study population. We report long-term outcomes in Chinese pts from these studies.

1017P AdvanTIG-105: Phase Ib dose-expansion study of ociperlimab (OCI) + tislelizumab (TIS) with chemotherapy (chemo) in patients (pts) with metastatic squamous (sq) and non-squamous (non-sq) non-small cell lung cancer (NSCLC)

T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) inhibitor + an anti-programmed cell death protein 1 (PD-1) antibody is a promising combination which shows potent efficacy in solid tumors. AdvanTIG-105 is a Phase 1/1b open-label study designed to assess the safety and preliminary antitumor activity of OCI, an anti-TIGIT monoclonal antibody (mAb), + TIS, an anti-PD-1 mAb, in pts with metastatic unresectable solid tumors (NCT04047862). In the dose-escalation part, OCI + TIS was well tolerated, preliminary efficacy was observed, and the recommended Phase 2 dose (RP2D) of OCI 900 mg intravenous (IV) every three weeks (Q3W) + TIS 200 mg IV Q3W was established. We report results from the dose-expansion (Cohorts 1 [C1] & 2 [C2]) of the AdvanTIG-105 study. Treatment-naïve adult pts with histologically/cytologically confirmed metastatic sq (C1) or non-sq with EGFR/ALK/ROS-1 wild-type tumors (C2) NSCLC were enrolled. Pts in C1 received the RP2D of OCI + TIS with paclitaxel/nab-paclitaxel + carboplatin and pts in C2 received the RP2D of OCI + TIS with pemetrexed + cisplatin/carboplatin, both until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included safety. As of March 18, 2022, 84 pts were enrolled (C1: n=41; C2: n=43). The median study follow-up was 17.7 weeks (range 1.1–42.6) in C1 and 15.0 weeks (3.0–51.1) in C2. Of the 76 efficacy-evaluable pts, the confirmed ORR in C1 was 45.9% (95% confidence interval [CI]: 0.3, 0.6) and 25.6% (95% CI: 0.1, 0.4) in C2. In total, 81 pts (96.4%) experienced ≥ 1 treatment-emergent adverse event (TEAE), and 48 pts (57.1%) had ≥ Grade 3 TEAEs. Serious TEAEs occurred in 26 pts (31.0%). The most common TEAEs were anemia (41.7%), neutrophil count decreased (33.3%), and white blood cell count decreased (33.3%). The RP2D of OCI 900 mg IV Q3W and TIS 200 mg IV Q3W + chemo was generally well tolerated and showed antitumor activity in pts with treatment-naïve metastatic sq/non-sq NSCLC. Prof. Y. Yu and Prof. D. Huang have contributed equally to the study.

Economic evaluation of sintilimab plus chemotherapy vs. pembrolizumab plus chemotherapy for the treatment of first-line advanced or metastatic squamous NSCLC.

Background and objectiveSintilimab has superior efficacy and safety in patients with advanced or metastatic squamous non-small cell lung cancer (NSCLC), but its cost-effectiveness in China is unclear. This study is to evaluate the cost-effectiveness of sintilimab plus chemotherapy vs. pembrolizumab plus chemotherapy for locally advanced or metastatic squamous NSCLC in China.MethodsFrom the perspective of the Chinese health system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime time horizon. The two-stage method was used to estimate the overall survival hazard ratios to avoid the bias by crossover design in ORIENT-12 and KEYNOTE-407 studies. The anchored matching adjusted indirect comparison method (MAIC) was used for indirect comparison based on the individual patient data from ORIENT-12 and the publicly published KEYNOTE-407 study due to the lack of head-to-head clinical trials. Only direct medical costs were included, and utilities were derived from the published literature in the base case analysis. Sensitivity analysis was also performed to verify the robustness of the model results. In addition, the scenario analysis where the utilities were derived from the Quality of Life Questionnaire-Core 30 (QLQ-C30) scale in the ORIENT-12 by mapping to the EuroQol-5-dimension 5-level (EQ-5D-5L) was carried out to explore the uncertainty of the results.ResultsCompared with pembrolizumab + chemotherapy, sintilimab + chemotherapy incurred a lower lifetime cost ($12,321 vs. 36,371) and yielded fewer quality-adjusted life-years (QALYs) (0.9902 vs. 1.0085), which resulted in an incremental cost-effectiveness ratio (ICER) of $1,314,208/QALY. A sintilimab strategy is a cost-effectiveness option under the WTP of 1–3 times the GDP per capita in China ($11,250/QALY~$33,749/QALY). The utility value of the post-progression, the unit cost of albumin paclitaxel, and the utility value of the progression-free state were the main drivers in the deterministic sensitivity analysis (DSA). According to the probabilistic sensitivity analysis (PSA), sintilimab + chemotherapy was 100% cost-effective when the WTP was 1–3 times China's per capita GDP. The results of the scenario analysis showed that sintilimab + chemotherapy obtained more QALYs (1.2319 vs. 1.1815) and lower costs ($12,321 vs. 36,371), which implied that sintilimab + chemotherapy may dominate the pembrolizumab + chemotherapy.ConclusionCompared with pembrolizumab + chemotherapy, sintilimab + chemotherapy is more cost-effective for first-line treatment in Chinese patients with locally advanced or metastatic squamous NSCLC.

150P Subgroup analysis of ORIENT12: Efficacy of sintilimab in combination with gemcitabine and platinum-based chemotherapy in patients with advanced or metastatic squamous non-small cell lung cancer

Sintilimab in combination with gemcitabine and platinum-based chemotherapy has shown good efficacy in a randomized, double-blind, phase 3 study in Chinese patients with squamous NSCLC (ORIENT 12). This subgroup analysis assessed the efficacy of sintilimab combination stratified by key baseline patient characteristics (PD-L1 expression level and disease staging).

168TiP KEYNOTE-A86: Phase III, randomized, open-label study of first-line subcutaneous (SC) vs intravenous (IV) pembrolizumab with platinum doublet chemotherapy in metastatic squamous or nonsquamous non-small cell lung cancer (NSCLC)

IV pembrolizumab is approved for several tumor types, including squamous and nonsquamous NSCLC. Because most patients prefer SC vs IV dosing, a SC formulation of pembrolizumab was developed, and was found to have similar pharmacokinetics (PK) to the IV formulation in the phase 1 KEYNOTE-555 study. The phase 3, randomized, multicenter, open-label KEYNOTE-A86 study (NCT04956692) evaluates the PK, safety, and efficacy of first-line SC vs IV pembrolizumab plus chemotherapy in metastatic squamous or nonsquamous NSCLC.

CLO21-020: Pembrolizumab in Metastatic Non-Squamous and Squamous Non-Small Cell Lung Cancer (NSCLC): Real World Data Results

CLO21-020: Pembrolizumab in Metastatic Non-Squamous and Squamous Non-Small Cell Lung Cancer (NSCLC): Real World Data Results

Nivolumab-Induced Thyroid Dysfunction

Nivolumab is one of human IgG4 monoclonal antibody belonging to the family of immune checkpoint inhibitors which acts by blocking ligand activation of programmed Cell death 1 receptor on T cells. Nivolumab has been approved for the management of patients with metastatic melanoma, metastatic squamous nonsmall cell lung carcinoma, renal cell carcinoma, and metastatic urothelial carcinoma. Associated side effects include increased risk of severe immune-mediated reactions involving the respiratory and gastrointestinal tracts, liver, kidney, and thyroid gland. Its effects on thyroid gland can result in hypothyroidism (7%), hyperthyroidism (1%), and thyroiditis (

PCN64 Cost-Effectiveness of Pembrolizumab (KEYTRUDA®) in Combination with Chemotherapy for First-LINE Treatment of Metastatic Squamous NON-SMALL Cell LUNG Cancer (NSCLC) in France

PCN64 Cost-Effectiveness of Pembrolizumab (KEYTRUDA®) in Combination with Chemotherapy for First-LINE Treatment of Metastatic Squamous NON-SMALL Cell LUNG Cancer (NSCLC) in France

1418TiP Randomized, placebo-controlled phase III study of 1L pembrolizumab (Pembro) plus carboplatin/taxane followed by pembro with or without maintenance olaparib in patients (Pts) with metastatic squamous non-small cell lung cancer (sqNSCLC): KEYLYNK-008

In KEYNOTE-407, 1L pembro + carboplatin-(nab)paclitaxel (chemo) significantly improved OS in metastatic sqNSCLC. The poly(ADP-ribose) polymerase inhibitor olaparib improved outcomes as maintenance therapy vs placebo in platinum-sensitive, newly diagnosed BRCA1/BRCA2–mutated (BRCAm) ovarian cancer and relapsed/recurrent BRCAm/BRCA wild-type ovarian cancer, suggesting efficacy in tumors with homologous recombination repair deficiency (HRD) regardless of BRCAm. High HRD scores in NSCLC suggest potential benefit with olaparib maintenance in pts with NSCLC.

A phase I study of ADXS-503 alone and in combination with pembrolizumab in subjects with metastatic squamous or non-squamous non-small cell lung cancer (NSCLC).

e21682 Background: ADXS-503 (A503) is an off-the-shelf, attenuated Listeria monocytogenes (Lm)-based immunotherapy bioengineered to elicit potent T cell responses against 22 tumor antigens commonly found in NSCLC (i.e., 11 hotspot mutations and 11 tumor-associated antigens, TAAs). Pembrolizumab (Pembro) is a programed death receptor-1 (PD-1)- blocking antibody with proven efficacy in NSCLC. A503 and Pembro have complementary mechanisms of immune activation and reversal of immune tolerance. Methods: This is a phase I study of A503 ± Pembro in patients (pts) with metastatic squamous or non-squamous NSCLC. Dose escalation with A503 alone has been tested at two dose levels (i.e., 1 and 5 x108 CFU) in Part A in pts refractory or intolerant to prior systemic therapy. In dose escalation Part B, A503 is being evaluated at the same dose levels (DLs) in combination with Pembro in pts with disease progression on Pembro. Part C will be a dose expansion cohort with A503 + Pembro as first-line treatment in the metastatic setting. A503 ± Pembro (200 mg) will be infused intravenously every 3 weeks until disease progression or limiting toxicity. Main endpoints include safety, tolerability and immune-correlative data. Results: Nine patients have been treated: 7 with A503-alone in Part A and two pts with A503+ Pembro in Part B-DL1. No pts in Part A experienced dose-limiting toxicities at the 2 DLs tested. Two Grade 3 adverse events occurred in one pt related to the infusion: hypertension and flu-like syndrome. A transient and manageable SAE (Grade 2 acute kidney injury) was possibly related to A503 alone at 5 x108 CFU. A503+ Pembro have been well tolerated in 2 pts in Part B-DL1. Four pts achieved a best overall response of stable disease, three in Part A and one in Part B. A503 alone induced immune responses in pts so far evaluated in Part A. Conclusions: ADXS-503 alone has demonstrated a manageable safety profile and immune responses in Part A. The 1x108 CFU was identified as the recommended phase II dose. Dose escalation with A503+ Pembro is ongoing and dose expansion in first line treatment is due to start shortly. Clinical trial information: NCT03847519.

CCTG BR.34: A randomized trial of durvalumab and tremelimumab +/- platinum-based chemotherapy in patients with metastatic (Stage IV) squamous or nonsquamous non-small cell lung cancer (NSCLC).

9502 Background: First-line therapy for advanced NSCLC includes PD-1 checkpoint inhibitor (ICI) monotherapy, and in combination with chemotherapy. Combination ICI have also demonstrated better survival compared to chemotherapy (CM-227). In CCTG BR.34, we compared overall survival (OS) in patients with advanced NSCLC receiving first-line durvalumab plus tremelimumab (DT) with or without platinum doublet chemotherapy (CT). Methods: This international, open-label, randomized trial accrued 301 participants from Canada and Australia, with stage IV NSCLC, EGFR/ALK wildtype, ECOG PS 0/1. Patients were randomized to DT for 4 cycles or DT+CT (pemetrexed- or gemcitabine-platinum), with ongoing D or D + pemetrexed (non-squamous) maintenance until disease progression. Stratification factors included histology, stage IVA v. IVB and smoking status. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR = CR + PR) and adverse events (AEs). Results: At a median follow up of 16.6 months, no significant difference in OS was seen between the two treatment arms, with a median OS of 16.6 months with DT+CT v. 14.1 months with DT, (estimated HR 0.88, 90% CI 0.67-1.16). PFS was significantly improved in the DT+CT arm (stratified HR 0.67, 95% CI 0.52-0.88; medians 7.7 v. 3.2 months). ORR was higher in the DT+CT arm, 28% v. 14%, (odds ratio 2.1, p=0.001). Preplanned subgroup analysis demonstrated no significant differences in treatment outcomes by plasma TMB (<20 v. ≥20 mut/Mb, Guardant OMNI), age, sex, or smoking status. There was a trend to improved OS with DT+CT in the subgroup with PD-L1 TPS≥50%, (HR 0.64, 95% CI 0.40-1.04, p=0.07). Plasma TMB<20 mut/Mb was associated with shorter survival in both treatment groups (HR 1.99, 95% 1.3-3.1). Toxicity was greater in the DT+CT arm, with grade≥3 adverse events in 82% v. 70%, (p=0.02), most commonly dyspnea, nausea and cough. The incidence of immune-related adverse events was similar between arms (colitis 11%, pneumonitis 6%, endocrinopathy 21%). Grade 5 events occurred in 2.7%, (5 with DT+CT, 3 with DT). Conclusions: The addition of CT to first-line DT did not improve OS in advanced NSCLC. CT+DT improved ORR and PFS, and was associated with greater toxicity. No differential effects were seen by PD-L1 TPS nor bTMB. These data suggest that adding chemotherapy to ICI may be beneficial in those with PD-L1 TPS >=50%, and warrant further analysis in independent datasets. Clinical trial information: NCT03057106 .

SAT-LB112 An Unusual Case of Ipilimumab/Nivolumab Induced Fulminant Diabetic Ketoacidosis (DKA) in a Non Diabetic Patient - a Case Report

SAT-LB112 An Unusual Case of Ipilimumab/Nivolumab Induced Fulminant Diabetic Ketoacidosis (DKA) in a Non Diabetic Patient - a Case Report

PCN194 COST-EFFECTIVENESS ANALYSIS OF PEMBROLIZUMAB IN COMBINATION WITH CARBOPLATIN AND PACLITAXEL FOR PREVIOUSLY UNTREATED PATIENTS WITH METASTATIC SQUAMOUS NON-SMALL CELL LUNG CANCER IN ENGLAND

To assess cost-effectiveness of pembrolizumab with carboplatin and paclitaxel (pembrolizumab combination) versus carboplatin plus paclitaxel (chemotherapy) or pembrolizumab monotherapy (in PDL1 ≥50% expressors) in previously untreated metastatic squamous non-small cell lung cancer (NSCLC). A three-state partitioned survival model was developed with a 30-year time horizon. The KEYNOTE-407(data cut off: April, 2018) trial informed the efficacy and adverse event parameters of pembrolizumab combination and chemotherapy. Overall survival (OS) was extrapolated using a piece-wise approach, utilising trial Kaplan-Meier data until week 52, and extrapolating overall survival beyond the trial using mortality risks for the chemotherapy group derived from an external real-world database (SEER) for the remainder of the time horizon, with a relative risk applied for pembrolizumab combination based on within-trial treatment efficacy. An indirect treatment comparison provided comparative effectiveness estimates of pembrolizumab combination versus pembrolizumab in PDL1 ≥50% expressors. Quality-adjusted life years (QALYs) were estimated using utilities derived from trial EQ-5D data. Resource use and unit costs were applied from an NHS perspective. The model demonstrated that pembrolizumab combination increases the life expectancy of patients from 1.76 to 3.29 discounted years, and from 1.27 to 2.42 discounted QALYs relative to chemotherapy use. The base case incremental cost-effectiveness ratio (ICER) versus paclitaxel plus carboplatin is £33,075, with a dominant result observed versus pembrolizumab monotherapy in PDL1 ≥50% expressors. The latter result should be interpreted with caution, as the hazard ratio for mortality is not statistically different between comparators and incremental QALYs are close to zero. Model results are most sensitive to assumptions around the extrapolation of overall survival data. The results of this cost-effectiveness analysis demonstrated that pembrolizumab combination is a cost-effective choice compared to standard of care therapies in the UK when considering a willingness to pay threshold of £50,000 per QALY, as per NICE end-of-life criteria.