Metastatic Non-squamous Non-small Cell Lung Research Articles

Cost-efficiency and budget-neutral expanded access modeling of pembrolizumab versus the novel PD-1 inhibitor toripalimab in locally advanced or metastatic nonsquamous non-small cell lung cancer

Aims To estimate in a panel of patients with locally advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with a programmed death receptor-1 inhibitor in the US in 2024 (1) the cost-efficiency of toripalimab regimens compared to pembrolizumab regimens; and (2) the budget-neutral expanded access to additional toripalimab cycles and regimens from accrued savings. Methods Simulation modeling of toripalimab + pemetrexed + carboplatin in nonsquamous NSCLC to a similar pembrolizumab regimen in a panel of 49,647 patients; utilizing two cost inputs (wholesale acquisition cost (WAC) at market entry and an estimated ex ante toripalimab price point of 80% of pembrolizumab average sales price (ASP)) plus administration costs over one and two years of treatment with treatment rates from 1%-10%. Scenario analyses with treatment durations equivalent to toripalimab and pembrolizumab trials’ median PFS were also conducted. Results In the WAC-based models, toripalimab saves $2,223 per patient per cycle and $40,014 over 1 year of treatment ($77,805 over 2 years). Extrapolated to the 49,647-patient panel, estimated 1-year savings range from $19,865,840 (1% treatment rate) to $198,658,399 (10% rate). Reallocating these savings permits budget-neutral expanded access to an additional 1,753 (1% rate) to 17,533 (10% rate) toripalimab maintenance cycles or to an additional 97 (1% rate) to 972 (10%) full 1-year toripalimab regimens with all agents. Two-year savings range from $38,628,022 (1% rate) to $386,280,221 (10%). Reallocating these efficiencies provides expanded access ranging from 3,409 (1% rate) to 34,093 (10%) additional toripalimab cycles or to 97 to 973 full 2-year regimens. The ex ante ASP model showed similar results as did the scenario analyses but at a lower magnitude than the base case. Conclusion Toripalimab generates significant savings that enable budget-neutral funding for up to 17,533 [34,093] additional maintenance cycles over one year [two years] with toripalimab + pemetrexed in nonsquamous NSCLC, or 972 [973] full one-year [two-year] regimens.

Real world results of locally advanced and metastatic lung cancer patients treated with platinum doublet chemotherapy in first line: Moroccan cohort

BackgroundDoublet platin-chemotherapy was the old standard treatment for different histology types of advanced and metastatic lung cancer (LC) and is still an option for patients who are not eligible for immune checkpoint inhibitors. However, in low- and middle-income countries, chemotherapy, either in monotherapy or in combination with platinum, is still the only accessible option in public institutions. The efficacy of different platin-based chemotherapy in patients with LC who are treatment-naïve is unknown. MethodsIn this retrospective study, we selected patients with advanced and metastatic (IIIB-IVB) non-squamous non-small cell LC (NSCLC), squamous NSCLC, and lung neuroendocrine tumours (small cell LC (SCLC), large cell neuroendocrine, and atypical carcinoid) aged beyond 18 years who received first-line chemotherapy (docetaxel, gemcitabine, etoposide, paclitaxel, pemetrexed, and vinorelbine) combined with platinum between January 1, 2013, and December 31, 2022. Within the population with non-squamous NSCLC, squamous NSCLC, and neuroendocrine tumours, progression-free survival (PFS) and overall survival (OS) were the primary assessed endpoints. Hematologic safety was the secondary endpoint. ResultsOverall, 611 patients were included. In the group of patients with non-squamous NSCLC (n = 390), there was no statistical difference between subgroups of patients who received first-line platin-chemotherapy. The median PFS was 182 (95 % confidence interval [CI], 167–208) days (hazard ratio for progression: NR [Not Reached]; p = 0.37), and the median OS was 446 (95 % CI, 405–559) days (hazard ratio for death: 1.31; 95 % CI, 0.94 - 1.82; p = 0.1). In the group of patients with squamous NSCLC (n = 149), we note the absence of statistical significance between subgroups of patients who received platin-based chemotherapy. The median PFS was 195 (95 % CI, 142–238; hazard ratio for progression: 1.21, 95 % CI, 0.29–5.02; p = 0.27), while the median OS was 428 (95 % CI, 324–940) days (hazard ratio for death: 1.76; 95 % CI, 0.93 to 3.3; p = 0.32). The absence of significance has been noticed in the neuroendocrine subgroup of patients who received first etoposide-platinum, vinorelbine-platinum, or paclitaxel-platinum (n = 72). The median PFS was 216 (95 % CI, 193–277) days; hazard ratio for progression: 1.74, 95 % CI, 0.41–7.27; p = 0.69, while the median OS was 273 (95 % CI, 241–459) days (hazard ratio for death: 2.95; 95 % CI, 0.4–21.7; p = 0.51). Grade 3–4 neutropenia grade was the predominant adverse event associated with chemotherapy in almost 11 % of patients. ConclusionMoving forward, treatment strategies must be refined for patients, with an emphasis on increasing the number of patients who can benefit from emergent approaches in order to guarantee a wider, deeper, and longer-lasting outcome.

PP01.53 Patient-Reported Outcomes (PROs) in Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC): PERLA Trial Comparing First-Line Chemotherapy Plus Dostarlimab or Pembrolizumab

PP01.53 Patient-Reported Outcomes (PROs) in Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC): PERLA Trial Comparing First-Line Chemotherapy Plus Dostarlimab or Pembrolizumab

Impact of maintenance pemetrexed cessation on clinical outcomes of patients with metastatic non-squamous NSCLC.

8568 Background: Combination chemoimmunotherapy including pemetrexed and a PD(L)1 inhibitor is a common first line systemic approach for patients with metastatic non-squamous non-small cell lung cancer (NSCLC). Patients often discontinue maintenance pemetrexed due to adverse effects, and little is known about the impact of maintenance pemetrexed cessation on progression free survival (PFS) and overall survival (OS). Methods: 121 patients with stage IV or recurrent, metastatic non-squamous NSCLC treated at VUMC were included in this retrospective analysis. Patients diagnosed between 7/2017- 9/2023 were included if they received maintenance pemetrexed and pembrolizumab. Patients were divided into two groups: those who stopped pemetrexed due to toxicity and those who did not. PFS and OS were measured from time of stage IV or metastatic diagnosis to the date of radiographic progression or death, respectively, and compared with the Kaplan Meier method. Results: Among patients with stage IV or recurrent, metastatic NSCLC (n = 121), who remained on maintenance pemetrexed and pembrolizumab (n=68), the median PFS was 11.7 months (95% CI, 7.47-NA) compared to 24.3 months (95% CI, 19.4-NA) among patients who stopped maintenance pemetrexed (n=53; p=0.1). The median OS in the same patient groups was 25.8 months (95% CI, 13.8-NA) compared to 36.4 months (95% CI, 26.9-NA) (p=0.15), respectively. Among patients with stage IV disease at diagnosis (n = 97), the median PFS among patients who did not stop pemetrexed was 8.7 months (95% CI, 7.2–NA) compared to 24.3 months (95% CI, 17.3-NA) for patients who stopped pemetrexed (p=0.089). The median OS in these groups were 21 months (95% CI, 13.6-NA) and 38.6 months (95%, 28.0-NA) (p=0.054), respectively. Conclusions: In this study of patients with metastatic non-squamous NSCLC who received maintenance pemetrexed and pembrolizumab, patients who stopped pemetrexed due to toxicity experienced similar outcomes to those who continued with pemetrexed. The necessity of continuation of maintenance chemotherapy should be further evaluated in the immunotherapy era. [Table: see text]

Cost-efficiency and expanded access modeling of toripalimab versus pembrolizumab in locally advanced or metastatic nonsquamous non-small cell lung cancer.

e20590 Background: Toripalimab, a novel anti-PD-1 antibody, demonstrated significant PFS and OS benefit in combination with pemetrexed and platinum (toripalimab+PemPlat) in advanced nonsquamous non-small cell lung cancer (nsNSCLC) over placebo+PemPlat in the CHOICE-01 trial (median PFS: 9.7 vs 5.5 months; median OS: NE vs 17.0 months), though not currently approved for this indication. FDA-approved pembrolizumab+PemPlat was similarly found to extend PFS and OS over placebo+PemPlat in metastatic nsNSCLC patients in KEYNOTE-189 (median PFS: 9.0 vs 4.9 months; median OS: 22.0 vs 10.7 months). The current wholesale acquisition cost (WAC) of pembrolizumab is $11,115 per dose. The WAC of toripalimab, recently approved for nasopharyngeal carcinoma, is 80% of pembrolizumab. In this simulation we modeled the cost-efficiency of the toripalimab regimen versus pembrolizumab in nsNSCLC and the budget-neutral expanded access to additional toripalimab enabled by savings. Methods: Utilizing WAC drug costs and treatment administration costs, we estimated the cost-efficiency of the toripalimab regimen for the median PFS 9.7 months observed in CHOICE-01 versus the pembrolizumab regimen for the median PFS 9.0 months observed in KEYNOTE-189. We assumed that 14 cycles of toripalimab+Pem (with carboplatin in cycles 1-4) are administered over 9.7 months and 13 cycles of pembrolizumab+Pem (with carboplatin in cycles 1-4) are administered over 9.0 months. From the differential, we estimated the potential expanded access to additional toripalimab treatment on a budget-neutral basis. The model was replicated utilizing an ex ante toripalimab average sales price (ASP) of 80% of pembrolizumab ASP. Results: The pembrolizumab regimen costs $176,705 over 9.0 months (13 cycles) while the toripalimab regimen costs $159,136 over 9.7 months (14 cycles) at the respective WACs, for savings of $17,569 per patient. This would enable the purchase of 1.6 additional toripalimab+pemetrexed maintenance cycles on a budget-neutral basis for every patient treated. For every 9 patients treated with toripalimab instead of pembrolizumab, one additional patient could be treated with the full toripalimab regimen (all agents) for 9.7 months. Extrapolated to the US incident nsNSCLC population of 49,647 patients, if only 5% of patients are treated with toripalimab instead of pembrolizumab estimated savings of $43,611,849 provide access to 3,849 additional toripalimab+pemetrexed maintenance cycles or 274 full toripalimab regimens (all agents for 9.7 months) budget-neutrally. Similar results were seen in the ex ante ASP model. Conclusions: If approved for use in advanced nsNSCLC, toripalimab is estimated, at its market-entry WAC, to save $17.6 thousand per patient over a median PFS 9.7 months treatment duration compared to the pembrolizumab regimen over a median PFS 9.0 months of treatment.

Pharmacoeconomic evaluation of first-line combination therapy with immunotherapy drugs and platinum-containing chemotherapy in adult patients with metastatic non-squamous non-small cell lung cancer

Objective: to evaluate the pharmacoeconomic efficacy of “atezolizumab + bevacizumab + paclitaxel + carboplatin” drug combination compared to “pembrolizumab + pemetrexed + carboplatin” combination in adult patients with non-small cell lung cancer (NSCLC) in the first line of therapy.Material and methods. The modeling was applied for cost minimization analyzis of using compared therapy regimens with comparable efficacy, and to estimate the impact on the healthcare budget when increasing the proportion of patients in the target population receiving “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination. Published adjusted indirect comparison data were used in modeling. The calculations were based on the registered prices according to the state register of maximum selling prices.Results. The use of “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination instead of “pembrolizumab + pemetrexed + carboplatin” combination will decrease the direct medical costs of therapy per 1 patient for 2 years by 28,165.00 rubles (–0.4%). The budget impact analysis showed that an increase in the proportion of patients receiving “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination from 50% (current therapy practice) to 100% (considered therapy practice) will reduce the budget load for the population of 6,240 patients over 2 years by 256.1 million rubles (–0.64%).Conclusion. The results of pharmacoeconomic analysis demonstrated that the use of “atezolizumab + bevacizumab + paclitaxel + carboplatin” combination in first-line therapy for metastatic NSCLC is economically feasible and reduces the load on the budget compared to “pembrolizu- mab + pemetrexed + carboplatin” scheme.

Abstract LB107: Association of circulating free DNA (cfDNA) maximum variant allele frequency (mVAF) levels with clinical outcomes in patients (pts) with metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with pembrolizumab (pembro) + chemotherapy (chemo) in the phase 2 KEYNOTE-782 trial

Abstract Background: The phase 2 KEYNOTE-782 trial (NCT03664024) was designed to prospectively evaluate plasma-derived biomarkers of response to first-line pembro + chemo in pts with metastatic nonsquamous NSCLC. This exploratory analysis of KEYNOTE-782 evaluated the association of cfDNA mVAF levels with clinical outcomes. Methods: Adults with untreated stage IV nonsquamous NSCLC received pembro 200 mg Q3W + chemo (pemetrexed + carboplatin or cisplatin). cfDNA was isolated from plasma samples collected at baseline (BL) and cycle 2 (C2) and sequenced using a targeted NGS-based assay previously used to assess blood tumor mutational burden from cfDNA for the primary analysis. cfDNA mVAF was quantified for each patient. The associations of BL cfDNA mVAF (all pts) and change in cfDNA mVAF from BL at C2 (pts with ≥1 detectable variant at BL; cfDNA+) as continuous variables with ORR, PFS, and OS were evaluated; 1-sided α was prespecified at 0.05 after multiplicity adjustment. ORR, PFS, and OS were also descriptively evaluated by cfDNA bins (BL mVAF, >0 vs 0; mVAF change from BL, ≥median vs <median). Results: Of 101 pts with evaluable cfDNA samples at BL, 83 (82.2%) were cfDNA+; 74 of these 83 pts had evaluable cfDNA samples at C2. Low BL mVAF was associated with improved ORR, PFS, and OS (P <0.01, each). The area under the receiver operating characteristic curve (AUROC) for discriminating response was 0.61 (95% CI, 0.50-0.72). Among pts with BL mVAF >0 (n = 83) vs 0 (n = 18), ORR (95% CI) was 38.6% (28.1-49.9) vs 55.6% (30.8-78.5), median PFS (95% CI) was 6.6 mo (4.9-9.0) vs 19.7 mo (9.8-not reached [NR]), and median OS (95% CI) was 13.6 mo (9.4-22.5) vs 31.6 mo (20.1-NR). Larger reductions in mVAF from BL at C2 were associated with improved ORR, PFS, and OS (P <0.05, each). The AUROC for discriminating response was 0.69 (95% CI, 0.57-0.82). After adjustment for best overall response, change in mVAF from BL at C2 was not associated with PFS or OS (P >0.05). In a descriptive evaluation for pts with a mVAF change from BL at C2 ≥median of 0.15 (n = 37) vs <median (n="37)," orr="" (95%="" ci)="" was="" 18.9%="" (8.0-35.2)="" vs="" 64.9%="" (47.5-79.8),="" median="" pfs="" 5.1="" mo="" (4.2-11.1)="" 7.2="" (6.2-21.7),="" and="" os="" 12.8="" (7.9-18.1)="" 25.9="" (15.3-nr).="" conclusions:="" in="" pts="" with metastatic nonsquamous NSCLC treated with pembro + chemo, low cfDNA mVAF levels at BL and larger reductions in cfDNA mVAF levels were associated with improved clinical outcomes. However, after correction for clinical response, the prognostic value of cfDNA mVAF reduction was not significant. Further studies are warranted to elucidate the utility of cfDNA for disease monitoring in this setting. Citation Format: Jair Bar, Emilio Esteban, Delvys Rodríguez-Abreu, Santiago Ponce-Aix, Zsuzsanna Szalai, Enriqueta Felip, Maya Gottfried, Mariano Provencio Pulla, Andrew Robinson, Andrea Fülöp, Suman Bannur Rao, D. Ross Camidge, Giovanna Speranza, Nathan Hunkapiller, Robert McDaniel, Byoungsok Jung, David Burkhardt, Ruth Mauntz, Cai Chen, Carol Pena, Razvan Cristescu, Elisha J. Dettman, Steven M. Townson, Julie Kobie, Tibor Csőszi. Association of circulating free DNA (cfDNA) maximum variant allele frequency (mVAF) levels with clinical outcomes in patients (pts) with metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with pembrolizumab (pembro) + chemotherapy (chemo) in the phase 2 KEYNOTE-782 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB107.

Abstract CT284: A phase 3 randomized controlled trial of zongertinib (BI 1810631) compared with standard of care in patients with locally advanced or metastatic nonsquamous non-small cell lung cancer harboring HER2 tyrosine kinase domain mutations: Beamion LUNG-2

Abstract Background: First-line (1L) standard of care for patients with HER2 mutation-positive (HER2m+) non-small cell lung cancer (NSCLC) is platinum-based chemotherapy ± immunotherapy. To date, no targeted 1L treatments have been approved. Zongertinib is a HER2-selective tyrosine kinase inhibitor that binds to wild-type and mutated HER2, and spares EGFR. In Phase Ia of Beamion LUNG-1 (NCT04886804), zongertinib conferred objective response/disease control rates of 49/91% in patients with pretreated HER2 aberration-positive solid tumors, and 58/97% in those patients with HERm+ NSCLC, with manageable safety with few EGFR-associated adverse events. Purpose: Here we describe Beamion LUNG-2 (NCT06151574), a phase 3, randomized, controlled, open-label trial that will compare the efficacy and safety of 1L zongertinib with standard of care in patients with HER2m+, locally advanced/metastatic nonsquamous NSCLC. Experimental design: Approximately 270 patients will be randomized 1:1 to receive either zongertinib or standard of care. Key inclusion criteria: histologically/cytologically diagnosed advanced/metastatic nonsquamous NSCLC; no prior systemic treatment for locally advanced/metastatic disease; HER2 mutation in the tyrosine kinase domain; ≥1 measurable lesion (RECIST 1.1). Key exclusion criteria: tumors that have alterations with available therapy, and radiotherapy/major surgery ≤4 weeks prior to randomization. In the experimental arm, oral zongertinib 120 mg once daily will be given in 21-day cycles. In the comparator arm, intravenous pemetrexed 500 mg/m2 chemotherapy plus either cisplatin 75 mg/m2 or carboplatin area under the curve 5, plus pembrolizumab 200 mg will be given on day 1 every 3 weeks for 4 cycles, followed by pemetrexed 500 mg/m2 plus pembrolizumab 200 mg every 3 weeks for ≤35 cycles. In both arms, treatment will continue until progressive disease (RECIST 1.1), undue toxicity, or other criteria are met. Primary endpoint: progression-free survival (RECIST 1.1). Secondary endpoints: overall response (defined as best overall response of complete or partial response, RECIST 1.1), patient-reported outcomes (changes from baseline to Week 25), overall survival, and adverse events during the on-treatment period (CTCAE 5.0). Citation Format: Yi-Long Wu, Melissa Johnson, Ross Soo, Navid Baktash, Daniela Maier, Sabina Eigenbrod-Giese, Tatsuya Yoshida. A phase 3 randomized controlled trial of zongertinib (BI 1810631) compared with standard of care in patients with locally advanced or metastatic nonsquamous non-small cell lung cancer harboring HER2 tyrosine kinase domain mutations: Beamion LUNG-2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT284.

A real-world retrospective, observational study of first-line pembrolizumab plus chemotherapy for metastatic non-squamous non-small cell lung cancer with PD-L1 tumor proportion score < 50% (PEMBROREAL).

The phase III Keynote-189 trial established a first-line treatment combining pembrolizumab with pemetrexed and platinum as a standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) without known EGFR and ALK driver mutations and independent of programmed cell death ligand 1 (PD-L1) expression. However, in Italy, eligibility for the National Health Service payment program is limited to patients with PD-L1 <50%. The PEMBROREAL study assesses the real-world effectiveness and safety of pembrolizumab in patients eligible for the National Health Service payment program. PEMBROREAL is a retrospective, observational study on patients with NSCLC who started pembrolizumab combined with pemetrexed and platinum within the reimbursability time window, considered as December 2019 to December 2020. The primary endpoints were to assess progression-free survival (PFS) and overall survival (OS; using the Kaplan-Meier method), response to therapy, and tolerability. Until February 2022, 279 patients (median follow-up: 19.7 months) have been observed. The median PFS was 8.0 months (95% confidence interval: 6.5-9.2). OS was not reached, but we can estimate a 12- to 24-month survival rate for the combined treatment: 66.1% and 52.5%, respectively. PD-L1 expression and Eastern Cooperative Group (ECOG) Performance Status were both associated with PFS and OS. Overall, only 44.4% of patients reported an adverse event, whereas toxicity led to a 5.4% discontinuation rate. The results of the PEMBROREAL study have shown that the combined treatment of pembrolizumab with pemetrexed and platinum is effective for metastatic non-squamous NSCLC, even for patients with PD-L1 levels below 50%, despite the differences in patient demographics and pathological features compared to the Keynote-189 study. The adverse events reported during the study were more typical of chemotherapy treatment rather than immunotherapy, and physicians were able to manage them easily.

102TiP A phase III randomised controlled trial of zongertinib (BI 1810631) compared with standard of care (SoC) in patients (pts) with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harbouring HER2 tyrosine kinase domain (TKD) mutations: Beamion LUNG-2

102TiP A phase III randomised controlled trial of zongertinib (BI 1810631) compared with standard of care (SoC) in patients (pts) with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harbouring HER2 tyrosine kinase domain (TKD) mutations: Beamion LUNG-2

Cost-Effectiveness Analysis of Sintilimab Plus Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer: A Societal Perspective.

The updated ORIENT-11 study demonstrated that sintilimab, when combined with chemotherapy, had promising survival advantage compared to standard chemotherapy alone in the first-line treatment for previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer (nsNSCLC). This study aims to evaluate the cost-effectiveness of sintilimab plus chemotherapy for advanced nsNSCLC from a Chinese societal perspective. A partitioned survival model with aembedded decision tree was developed to assess the economic value of sintilimab plus chemotherapy over a lifetime horizon. Clinical data was captured from the updated ORIENT-11 study, while costs, health productivity losses, and utility values were collected from a nationwide cross-sectional survey in tertiary hospitals across multiple provinces in China. The primary outcomes were measured using the metrics of quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER). Costs and health outcomes were discounted at an annual rate of 5% per annum. Sensitivity analyses, including one-way and probabilistic sensitivity analyses, subgroup analyses, and scenario analyses, were performed. Compared to standard chemotherapy, treatment with sintilimab plus chemotherapy incurred a mean total cost of $23,979 and gained 0.98QALYs over the lifetime horizon, resulting in an ICER of $24,568 per QALY gained. The use of sintilimab accumulated direct non-medical costs of $9262 and indirect costs of $6780 over 16years. Probabilistic sensitivity analyses showed an 84.2% probability of sintilimab plus chemotherapy being cost-effective at a threshold of three times China's per capita gross domestic product in 2022 ($38,201). The model was most sensitive to the discount rate of QALYs and costs, as well as the costs of pemetrexed, sintilimab, and subsequent therapy in progressive disease state. Subgroup analyses indicated favorable incremental net monetary benefits in all subgroups. Sintilimab plus chemotherapy is a cost-effective first-line treatment therapy for advanced nsNSCLC in China when compared to standard chemotherapy. These findings, along with the improved progression-free survival and overall survival (OS)observed in ORIENT-11, support the use of this regimen in eligible candidates for advanced nsNSCLC.

Prevalence of asymptomatic brain metastases in metastatic nonsquamous nonsmall cell lung cancer: Treatment implications for resource-constrained settings

Abstract Background: Brain metastases (BM) are common in metastatic nonsmall cell lung cancer (NSCLC). However, routine neuroimaging in asymptomatic patients with metastatic NSCLC is controversial as there is no conclusive evidence of benefit from the detection and treatment of asymptomatic BM. Herein, we evaluated the prevalence of asymptomatic BM and its treatment implications in a resource-limited setting. Methods: Consecutive patients with newly diagnosed, treatment-naïve, metastatic, nonsquamous NSCLC (NS-NSCLC) were included. Subjects who already had clinical or radiological features suggestive of BM were excluded from the study. All eligible subjects underwent contrast-enhanced magnetic resonance imaging (MRI) of the brain. Management of the detected BM was at the discretion of the treating clinicians. Results: Among 809 subjects who were screened, 100 (12.4%) were included in the study and underwent MRI. BM was present in 30 (30%) of the subjects and absent in the remaining 70 subjects. A majority of BM were multiple (70%), involved the frontal lobe commonly (73.3%), and had a mean (standard deviation) size of 13.2 (7.3) mm. Detection of BM resulted in a treatment alteration in 17 (17%) of the study subjects (brain irradiation, n = 17, change in targeted therapy, n = 3) with BM. There was no difference in survival of patients who underwent treatment alteration for management of BM compared to those who did not (P = 0.132). Conclusions: About one-third of patients with metastatic NS-NSCLC had BM in MRI despite the absence of symptoms. Despite treatment of the majority of the patients with BM with brain irradiation, there was no demonstrable survival benefit. Hence, we conclude that although routine neuroimaging of asymptomatic patients with newly diagnosed metastatic NSCLC may result in treatment alteration (primarily brain irradiation) in a small proportion of patients, it may not influence outcomes in resource-constrained settings.

OP11 Cost-Effectiveness Of Atezolizumab Plus Chemotherapy As A First-Line Treatment For Metastatic Non-Squamous Non-Small Cell Lung Cancer

IntroductionTreatment with atezolizumab plus standard chemotherapy can prolong the overall survival of patients with metastatic non-squamous non-small cell lung cancer (NSCLC). However, the economic value of this treatment regimen is unknown. This study aimed to estimate the cost effectiveness of atezolizumab plus chemotherapy in the first-line treatment of metastatic non-squamous NSCLC from a healthcare system perspective in China.MethodsA partitioned survival model consisting of three discrete health states was developed to estimate the cost and effectiveness of atezolizumab plus carboplatin or cisplatin plus pemetrexed (APP) versus carboplatin or cisplatin plus pemetrexed (PP) in the first-line treatment of metastatic non-squamous NSCLC over a 12-year lifetime horizon. Key clinical data were generated from the IMpower132 trial. Local direct medical and non-medical costs were used and health preference data were collected from patients with NSCLC in 13 tertiary hospitals across five provinces in China. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the model.ResultsCompared with the PP regimen, APP therapy yielded a gain of 0.21 QALYs at an increased cost of CNY145,602 (USD22,574), resulting in an ICER of CNY684,894 (USD106,185) per QALY gained. The ICER was significantly higher than three times the gross domestic product per capita for China in 2021 (USD37,663). One-way sensitivity analyses revealed that one of the most influential factors in this model was the cost of atezolizumab. Probabilistic sensitivity analysis showed that there was 14.7% probability that atezolizumab plus chemotherapy was cost effective at a willingness-to-pay value of CNY242,928 (USD37,663) per QALY gained.ConclusionsThe APP regimen could prolong survival and improve health benefits over standard chemotherapy in the first-line treatment of patients with metastatic non-squamous NSCLC, but it is unlikely to be a cost-effective treatment option in China.

81P Real-world experience with docetaxel regimens in metastatic non-squamous (mNSq) non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy (PCT) and an immune checkpoint inhibitor (ICI) in the United States (US)

81P Real-world experience with docetaxel regimens in metastatic non-squamous (mNSq) non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy (PCT) and an immune checkpoint inhibitor (ICI) in the United States (US)

Dostarlimab or pembrolizumab plus chemotherapy in previously untreated metastatic non-squamous non-small cell lung cancer: the randomized PERLA phase II trial

PERLA is a global, double-blind, parallel phase II trial (NCT04581824) comparing efficacy and safety of anti–PD-1 antibodies dostarlimab and pembrolizumab, plus chemotherapy (DCT and PCT, respectively) as first-line treatment in patients with metastatic non-squamous NSCLC without known targetable genomic aberrations. Patients stratified by PD-L1 tumor proportion score and smoking status were randomized 1:1, receiving ≤35 cycles 500 mg dostarlimab or 200 mg pembrolizumab, ≤35 cycles 500 mg/m2 pemetrexed and ≤4 cycles cisplatin (75 mg/m2) or carboplatin (AUC 5 mg/ml/min) Q3W. Primary endpoint was overall response rate (ORR) (blinded independent central review). Secondary endpoints include progression-free survival (PFS) based on investigator assessment, overall survival (OS) and safety. Exploratory endpoints include ORR by PD-L1 subgroup and duration of response. PERLA met its pre-specified endpoint. ORR (n/N; 95% CI) is 45% (55/121; 36.4–54.8) for DCT and 39% (48/122; 30.6–48.6) for PCT (data cut-off: 07 July 23), numerically favoring dostarlimab in PD-L1-positive subgroups. Median PFS (months [95% CI]) is 8.8 (6.7–10.4) for DCT and 6.7 (4.9–7.1) for PCT (HR 0.70 [95% CI: 0.50–0.98]; data cut-off: 04 August 22). Median OS (months [95% CI]) is 19.4 (14.5–NR) for DCT and 15.9 (11.6–19.3) for PCT (HR 0.75 [95% CI: 0.53–1.05]) (data cut-off: 07 July 23). Safety profiles are similar between groups. In this study, DCT shows similar efficacy to PCT and demonstrates clinical efficacy as first-line treatment for patients with metastatic non-squamous NSCLC.

LBA13 Dostarlimab + chemotherapy (CT) vs pembrolizumab + CT in metastatic non-squamous non-small cell lung cancer (NSCLC): Updated Asian subgroup analyses of the PERLA trial

LBA13 Dostarlimab + chemotherapy (CT) vs pembrolizumab + CT in metastatic non-squamous non-small cell lung cancer (NSCLC): Updated Asian subgroup analyses of the PERLA trial

1507TiP Phase Ib multicenter study of trastuzumab deruxtecan (T-DXd) and immunotherapy with or without chemotherapy in first-line treatment of patients (pts) with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) and HER2 overexpression (OE): DESTINY-Lung03

1507TiP Phase Ib multicenter study of trastuzumab deruxtecan (T-DXd) and immunotherapy with or without chemotherapy in first-line treatment of patients (pts) with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) and HER2 overexpression (OE): DESTINY-Lung03

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.

Phase 1b/2a safety and tolerability study of bemcentinib (BEM) with pembrolizumab/carboplatin/pemetrexed in first line (1L) advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) without/with a STK11 mutation.

TPS9154 Background: The combination of platinum, pemetrexed, and pembrolizumab (CIT) has become the standard of care in 1L non–oncogene addicted NSCLC. Despite an initial improvement in response rate and survival, the 5-year survival of NSCLC remains approximately 20-30%, due to the emergence of primary and acquired resistance. Additionally, the presence of brain metastases occurs in ˜30-50% of NSCLC patients and confers a poor prognosis. Among the currently non-actionable mutations, STK11/LKB1 mutations (STK11m) are common (˜20%) in NSCLC. Recent evidence suggests that STK11m NSCLC patients have a minimal response to checkpoint inhibitors and to chemo-immunotherapy in the first line setting. STK11m tumors are characterized by an immune-suppressed phenotype which is highly associated with AXL signalling. BEM, a first-in-class, oral, selective AXL inhibitor, has demonstrated the ability to prevent chemoresistance, re-sensitize STK11m NSCLC tumors to pembrolizumab, and enhance efficacy of CIT in preclinical lung models. Moreover, following oral administration, BEM readily distributes in brain tumour tissue in recurrent glioblastoma patients, with a 25.9 mean ratio of drug concentration in brain tissue to plasma. Therefore, the addition of BEM to CIT has the potential to improve 1L treatment outcomes in NSCLC overall and particularly in STK11m tumors. Methods: This is an open-label, multi-center, phase 1b/2a study to assess the safety, tolerability, and preliminary anti-tumor activity of BEM + CIT as 1L treatment in patients with advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC without actionable mutations. Patients with stable brain metastases are eligible to participate. Phase 1b follows a 3+3 design and will explore CIT in combination with one of 3 BEM dose levels: Cohort 1 = 75mg; Cohort 2 = 100 mg; or Cohort 3 = 150 mg. BEM is administered orally once/day on Day 1 of each 21-day treatment cycle. After 4 cycles of CIT + BEM, maintenance with BEM + pemetrexed + pembrolizumab is administered for up to 2 years. An independent data safety monitoring board will assess the safety data at the end of the dose-limiting toxicity period (the first 21 days of treatment for each patient, i.e. cycle 1) of each cohort and will recommend the BEM dose for the phase 2a expansion. In the phase 2a, up to 40 patients harboring a STK11m (regardless of their co-mutational status), in the absence of driver mutations will be enrolled. The study will include extensive co-mutational analyses via next-generation sequencing to identify potential sub-groups of patients deriving particular benefit. The trial is open to patient enrolment in phase1b in the US; recruitment for phase 2a is planned to open in Q2 2023 in Europe and US. EudraCT 2019‐003806‐28/NA/124645. Clinical trial information: NCT05469178 .

Patient-reported outcomes in patients with metastatic non-squamous non-small cell lung cancer from the PERLA trial comparing first-line chemotherapy plus dostarlimab or pembrolizumab.

9099 Background: PERLA (NCT04581824) is a global, randomized, Phase II, double-blind study assessing the efficacy and safety of chemotherapy (CT) combined with programmed death 1 (PD-1) inhibitors dostarlimab (dostCT) and pembrolizumab (pembCT) as first-line (1L) treatment (tx) for patients (pts) with metastatic non-oncogene-driven, non-squamous, NSCLC. DostCT had similar efficacy and safety to pembCT [1]. Exploratory analyses of patient-reported outcomes (PROs) from PERLA have been conducted. Methods: In PERLA, pts with ECOG status 0–1 were randomized 1:1 to receive ≤35 cycles (C) of dostCT or pembCT Q3W (CT was ≤35 cycles [C] of 500 mg/m2 pemetrexed every 3 weeks [Q3W] and ≤4C of cisplatin or carboplatin). PROs were collected at baseline (BL), Q3W until C4, Q9W until C16, Q12W until end of tx and at 30-day safety follow-up. Change from BL in EORTC QLQ-C30 &amp; QLQ-LC13 were analyzed using a longitudinal mixed model, with a ≥10-point change from BL considered clinically meaningful; scores were categorized as improved, stable, or worsened. Time to deterioration (TTD) in QLQ-C30 and selected QLQ-LC13 symptoms were estimated using Kaplan–Meier methods. Results: Analysis populations for dostCT/pembCT included 102/99 pts for QLQ-C30 and 96/90 pts for QLQ-LC13. Completion rates for QLQ-C30 and QLQ-LC13 were &gt;80% up to C4 in both tx arms, decreasing after C7. At C13, 55.0% [n=33/60] and 54.2% [n=32/59] of dostCT pts, and 37.1% [n=23/62] and 35.7% [n=20/56] of pembCT pts completed QLQ-C30 and QLQ-LC13, respectively. Overall, least squares (LS) mean QLQ-C30 and QLQ-LC13 scores remained stable up to C13. Relative to BL, average pt functioning (e.g., physical, role) and cancer symptoms (e.g., pain, cough, dyspnea) were stable through C13 (~1 yr on tx); no clinically meaningful difference in LS mean QLQ-C30 or QLQ-LC13 scores were observed between tx arms. Across most QLQ-C30 and QLQ-LC13 subscales, &gt;60% pts in both tx arms had stable or improved responses up to C13. At C13, meaningful improvements in chest pain and dyspnea were reported in a higher % of dostCT pts (34.4% [n=11/32] and 40.6% [n=13/32], respectively) than pembCT pts (10.0% [n=2/20] and 25.0% [n=5/20], respectively). TTD for QLQ-C30 and QLQ-LC13 subscales were comparable between tx arms, except for longer median TTD in dyspnea in dostCT pts (N=96) than pembCT pts (N=90) (4.24 vs 1.54 months; HR 0.64 [95% CI: 0.44–0.93]). Conclusions: HRQoL was similar and stable through C13 in both tx arms. These results supplement efficacy and safety data reported in PERLA and support further investigation of dostarlimab as an appropriate PD-1 inhibitor for use in combination with standard of care and novel therapies in metastatic NSCLC.