Advanced Squamous Non-small Cell Lung Research Articles

Immunological characteristics of peripheral T cells as prognostic markers for Camrelizumab and Apatinib combination therapy in advanced squamous non-small-cell lung cancer.

To determine the characteristic changes of peripheral blood T cells and identify potential biomarkers that associated with the clinical efficacy of combined immunotherapy and anti-angiogenic therapy in patients with advanced squamous non-small cell lung cancer (NSCLC). We performed a comprehensive immunological assessment of peripheral blood mononuclear cell samples from advanced squamous NSCLC patients before and after combination of immunotherapy (Camrelizumab) and anti-angiogenic therapy (Apatinib) using spectral flow cytometry. Correlations between these immunological features and clinical efficacy were analyzed. Our findings revealed that, following two treatment cycles, the concentration of type 1 T helper (Th1) cells in the peripheral circulation was significantly higher in the responder group than in the non-responder group, correlating with a statistically significant improvement in survival outcomes. Post-treatment, CD137 expression within Th1 cells in the responders, whereas TIM-3 expression was significantly reduced. In the validation cohort, elevated CD4+ CXCR3+ CD137+ cells in the peripheral blood were associated with a positive clinical reaction to the treatment and extended survival. Our findings suggest that peripheral blood circulating CD4+ CXCR3+ CD137+ cells serve as biomarkers of response to combined immunotherapy and anti-angiogenic therapy in patients with advanced squamous NSCLC, providing potential guidance for improving clinical outcomes.

An open-label, randomized phase III study of early switch maintenance vs delayed second-line nivolumab in advanced stage squamous non-small cell lung cancer (NSCLC) patients after standard first-line platinum-based chemotherapy-EDEN trial GOIRC 04-2016.

As for squamous (Sq)-NSCLC, Checkmate-017 trial showed a significant overall survival (OS) improvement in favor of Nivolumab (Nivo) over Docetaxel in 2nd-line. We hypothesized that anticipating Nivo use, as early switch maintenance after 1st-line chemotherapy (CHT), might have improved survival as compared to delayed 2nd-line treatment. EDEN was an open-label, 2-arm, phase III study which randomized (1:1) stage IIIB/IV Sq-NSCLC pts non-progressive after 1st-line platinum-based CHT, to receive early Nivo as switch maintenance (Arm A) or standard best supportive care followed by 2nd-line Nivo at disease progression (Arm B). In both arms, Nivo was administered at the dose of 240mg i.v. every 2weeks until progressive disease, intolerable toxicity, or for a maximum of 2years. The primary endpoint was OS. From Sep 2017 to Aug 2020 125 patients (62 Arm A vs 63 Arm B) were randomized from 32 Italian centers. Accrual was stopped early, before the planned sample size (388 pts) was reached, because of registration of ICPIs in 1st-line. Most patients were male (79.2%), current/former smokers (93.6%), had stage IV (74.4%), performance status 0-1 (98.4%). mOS (95% CI) was 14.9 (10.4-18.6) months in arm A vs 18.8 (14.4-21.1) months in arm B (HR 1.09, 95%CI 0.74-1.62, p=0.659). In advanced Sq-NSCLC, the use of Nivo as switch maintenance after 1st-line CHT, does not improve OS compared to its use as 2nd-line. Although the optimal use of ICPIs remains in 1st-line, its role as maintenance has to be better investigated. gov: registration number: NCT03542461.

P3.12D.09 Trial in Progress: A Phase Ib Study of HMBD-001, An Anti-HER3 Antibody, in Advanced Squamous Non-Small Cell Lung Cancer

P3.12D.09 Trial in Progress: A Phase Ib Study of HMBD-001, An Anti-HER3 Antibody, in Advanced Squamous Non-Small Cell Lung Cancer

Comparison of Nivolumab with Docetaxel in the Treatment of Advanced Squamous Cell Non-small Cell Lung Cancer

Lung squamous-cell carcinoma poses a significant global health challenge with limited treatment options available. Immune checkpoint inhibitors, particularly nivolumab, have revolutionized cancer therapy, especially in non-small cell lung cancer (NSCLC). Nivolumab, targeting the PD-1 protein, exhibits promise in treating advanced squamous-cell NSCLC. This article critically examines nivolumab’s development and compares its efficacy with docetaxel in this context. Nivolumab’s effectiveness lies in its ability to block the PD-1/PD-L1 immune checkpoint pathway, reinvigorating the immune response against cancer cells. Clinical trials reveal higher overall survival rates and fewer adverse events (AEs) with nivolumab compared to docetaxel, alongside improvements in patient-reported outcomes and mental well-being. However, limitations exist, primarily stemming from clinical trial data’s potential mismatch with real-world scenarios. Short trial durations hinder long-term outcome analysis and delay AE evaluations. Furthermore, the comparison is restricted to nivolumab and docetaxel, overlooking other Food and Drug Administration-approved monoclonal antibodies. Addressing these limitations are crucial for enhancing the utility of these evaluations in clinical decision-making and guiding future research in advanced squamous-cell NSCLC management. Nivolumab emerges as a promising treatment option, offering superior efficacy and safety over traditional chemotherapy, yet its real-world efficacy warrants further exploration.

Chemotherapy related changes in cfDNA levels in squamous non-small cell lung cancer: correlation with symptom scores and radiological responses.

There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses. Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC (n = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); n = 27] and healthy-controls (n = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy. At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days vs. 298 days and median PFS = 97 days vs. 197 days; P = 0.025; hazard ratio (HR) = 2.17]. Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.

Cost-effectiveness of immunotherapies for advanced squamous non-small cell lung cancer: a systematic review

BackgroundThere are differences in the pharmacoeconomics of Immune checkpoint blocking (ICB) therapies for the treatment of lung squamous cell carcinoma (LSCC). However, no corresponding review studies have fully discussed the cost-effectiveness of ICBs in treating LSCC. The aim of this paper is to systematically review and evaluate all available pharmacoeconomic studies of ICBs for LSCC.MethodThe inclusion criteria were based on the population, intervention, comparator, outcomes, and study designs. An electronic search was conducted by June 2023, and the following databases were used: PubMed, EMBASE, Cochrane Library, and Web of Science. Search keywords included ‘Carcinoma’, Non-Small-Cell Lung’, ‘Immunotherapy’, and ‘Economics, Medical’. The primary outcome was the cost-effectiveness analysis of ICB therapy in LSCC patients. Drummond Checklist was used to assess quality problems and possible bias in the study design of included pharmacoeconomic studies.ResultsThis review searched 15 articles on the economic evaluation of ICB treatment for LSCC. After a qualitative review of 15 studies, we concluded that nivolumab is more cost-effective as a monotherapy than chemotherapy alone. In the combination regimen, pembrolizumab combined with chemotherapy appears to be the most cost-effective option at present, but for Chinese payers with LSCC, locally developed treatments such as sintilimab or toripalimab in combination with chemotherapy are more cost-effective.DiscussionThe inclusion of economic evaluation has heterogeneity in research design and outcomes, which can only support qualitative synthesis. Therefore, The results of this paper need to be treated with caution. For the Chinese market, instead of imported drugs, the possible cost-effectiveness of locally developed ICB therapies should be the focus of future research.

62P First-line (1L) camrelizumab plus chemotherapy (chemo) for advanced squamous non-small cell lung cancer (sqNSCLC): 4-yr update from the phase III CameL-sq trial

62P First-line (1L) camrelizumab plus chemotherapy (chemo) for advanced squamous non-small cell lung cancer (sqNSCLC): 4-yr update from the phase III CameL-sq trial

539P Biomarker analysis of IBI110 (anti-LAG-3 mAb) in combination with sintilimab (anti-PD-1 mAb) and chemotherapy as 1L treatment for advanced squamous non-small cell lung cancer (sqNSCLC)

539P Biomarker analysis of IBI110 (anti-LAG-3 mAb) in combination with sintilimab (anti-PD-1 mAb) and chemotherapy as 1L treatment for advanced squamous non-small cell lung cancer (sqNSCLC)

540P Phase III study of serplulimab plus chemotherapy as first-line therapy for advanced squamous non-small cell lung cancer: ASTRUM-004 Asian subgroup

540P Phase III study of serplulimab plus chemotherapy as first-line therapy for advanced squamous non-small cell lung cancer: ASTRUM-004 Asian subgroup

Cost-effectiveness of camrelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer.

Objectives: A cost-effectivenessstudyof camrelizumab plus chemotherapy for advanced squamous non-small-cell lung cancerin China was conducted versus chemotherapy alone. Methods: Survival data were derived from CameL-Sq. Cost-effectiveness is indicated by an incremental cost-effectiveness ratio (ICER) less than the willingness-to-pay threshold. The partitioned survival model stability was assessed by sensitivity analyses. Results: With camrelizumab plus chemotherapy, quality-adjusted life years increased by 0.83, and cost increased by $21,259/patient versus chemotherapy. The ICER was $25,674/quality-adjusted life year. The probability of cost-effectiveness was >90% regardless of PD-L1 expression level. Regardless of the variation in each parameter across a wide range, the ICER never transcended the willingness to pay. Conclusion: Camrelizumab plus chemotherapy is a cost-effective first-line treatment for advanced squamous non-small cell lung cancer in China.

Cemiplimab + Chemo Shows Clinical Benefit in Advanced NSCLC

Cemiplimab + Chemo Shows Clinical Benefit in Advanced NSCLC

Phase 2 clinical trial of the proautophagic drug ABTL0812 combined with paclitaxel and carboplatin in first-line patients with advanced squamous non-small cell lung carcinoma.

9059 Background: ABTL0812 induces the inhibition of Akt/mTOR pathway by upregulation of TRIB3 protein, an endogenous Akt inhibitor, and promotes endoplasmic reticulum (ER) stress. As a result, ABTL0812 induces cytotoxic autophagy that leads to specific death of cancer cells, without affecting non-tumor cell viability. A Phase II clinical trial was designed where ABTL0812 was evaluated in combination with paclitaxel and carboplatin in first-line patients with advanced squamous non-small cell lung cancer (NSCLC). Methods: ABTL0812 was administered 1300 mg TID orally with 175 mg/m2 paclitaxel and AUC5 carboplatin every 3 weeks, for up to 8 cycles, followed by ABTL0812 as a maintenance until disease progression or unacceptable toxicity. The study enrolled patients with non-irradiable IIIb stage or stage IV squamous NSCLC. Primary endpoint was overall response rate (ORR) by RECIST criteria v.1.1. Secondary endpoints were progression free survival (PFS), overall survival (OS), duration of response (DOR), safety and tolerability according to CTCAE v4.03, pharmacokinetics (PK) of ABTL0812 enantiomers ((-)-ABTL and (+)-ABTL) and pharmacodynamics assessed by two surrogate blood biomarkers: TRIB3 and CHOP. Results: Forty patients were included; median age was 66.1 years old; 90% men/10% women; 100% ECOG 0-1; 30% current smokers/67.5% former smokers and 37.5% had received prior chemotherapy > 12 months before inclusion. 39 patients had at least 1 adverse event (AE), anemia appeared in 32.5% of the patients (5.0% grade 3), neutropenia in 27.5% (25% grades 3-4) and thrombocytopenia in 17.5% of the patients (2.5% grade 3). For non-hematological AEs, asthenia was reported in 62.5% of the patients (2.5% grade 3); diarrhea in 45% (no grade 3-4) and nausea in 37.5% (5% grades 3-4). Twenty-five patients reach the primary endpoint for efficacy evaluation. ORR was 52.0% (95% CI 34.2-65.9) and 32.0% of the patients had stable disease. Median OS was 22.5 months (10.4-NC), median progression free survival 6.2 months (4.4-8.8), and DOR 5.1 months (3.9-7.4). Area under the curve (µg·h/ml) for (-)-ABTL and (+)-ABTL were 39.0±12.3 and 17.1±6.3 respectively, maximal concentrations (µg/ml) were 6.4±2.6 and 5.1±2.2 and minimum concentrations (µg/ml) 2.2±1.5 and 0.8±1.3. TRIB3 and CHOP PD biomarkers were induced by the treatment. Conclusions: The combination of ABTL0812 with paclitaxel and carboplatin shows survival outcomes that compare favorably with historical controls in squamous-NSCLC with an acceptable safety profile. PK analysis is compatible with drug activity, and pharmacodynamic analysis shows drug engagement. Clinical trial information: NCT03366480 .

Economic Evaluation of Nivolumab Versus Docetaxel for the Treatment of Advanced Squamous and Non-squamous Non-small Cell Lung Cancer After Prior Chemotherapy in China.

To evaluate the economic value of nivolumab versus docetaxel for advanced non-small cell lung cancer (aNSCLC) treatment after platinum-based chemotherapy in adults without epidermal growth factor receptor/anaplastic lymphoma kinase aberrations in China. Partitioned survival models evaluated lifetime costs and benefits of nivolumab versus docetaxel by squamous and non-squamous histologies from a Chinese healthcare payer perspective. Progression-free disease, progressed disease, and death health states were considered over a 20-year time horizon. Clinical data were derived from the CheckMate pivotal Phase III trials (ClinicalTrials.gov identifiers: NCT01642004, NCT01673867, NCT02613507); patient-level survival data were extrapolated using parametric functions. China-specific health state utilities, healthcare resource utilisation, and unit costs were applied. Sensitivity analyses explored uncertainty. Nivolumab resulted in extended survival (1.489 and 1.228 life-years [1.226 and 0.995 discounted]) and quality-adjusted survival benefits (1.034 and 0.833 quality-adjusted life-years) at additional costs of ¥214,353 (US$31,829) and ¥158,993 (US$23,608) versus docetaxel in squamous and non-squamous aNSCLC, respectively. Nivolumab was associated with higher acquisition costs, lower subsequent treatment costs, and lower adverse event management costs than docetaxel in both histologies. Drug acquisition costs, discount rate for outcomes, and average body weight were key model drivers. Stochastic results aligned with the deterministic results. Nivolumab yielded survival and quality-adjusted survival benefits at incremental cost versus docetaxel in aNSCLC. As a traditional healthcare payer perspective was applied, the true economic benefit of nivolumab may be underestimated as not all treatment benefits and costs of relevance to society were considered.

Effectiveness and cost-effectiveness analysis of 11 treatment paths, seven first-line and three second-line treatments for Chinese patients with advanced wild-type squamous non-small cell lung cancer: A sequential model.

A total of 11 treatment sequences for advanced wild-type squamous non-small cell lung cancer are recommended by Chinese Society of Clinical Oncology Guidelines, consisting of seven first-line and three second-line treatments. Five of these treatments were newly approved in China between 2021 and 2022. We evaluated the effectiveness and cost-effectiveness of these strategies from the Chinese healthcare system perspective. Network meta-analysis with non-proportional hazards was used to calculate the relative efficacy between interventions. A sequential model was developed to estimate costs and quality-adjusted life years (QALY) for treatment sequences with first-line platinum- and paclitaxel-based chemotherapy (SC) with or without nedaplatin, tislelizumab, camrelizumab, sintilimab, sugemalimab or pembrolizumab, followed by second-line docetaxel, tislelizumab or nivolumab. SC and docetaxel were used as comparators for first-line and second-line treatments, respectively. QALY and incremental cost-effectiveness ratio (ICER) were used to evaluate effectiveness and cost-effectiveness, respectively. Cost-effective threshold was set as USD 19,091. Subgroup analysis was conducted to determine the best first-line and second-line therapy. Pembrolizumab + SC, followed by docetaxel (PED) was the most effective treatment sequence. QALYs for patients received SC, nedaplatin + SC, tislelizumab + SC, sintilimab + SC, camrelizumab + SC, sugemalimab + SC, pembrolizumab + SC followed by docetaxel were 0.866, 0.906, 1.179, 1.266, 1.179, 1.266, 1.603, 1.721, 1.807; QALYs for SC, nedaplatin + SC followed by tislelizumab were 1.283, 1.301; QALYs for SC, nedaplatin + SC followed by nivolumab were 1.353, 1.389. Camrelizumab + SC, followed by docetaxel (CAD) was the most cost-effective. Compared to SC with or without nedaplatin, tislelizumab, or sintilimab followed by docetaxel, ICERs of CAD were USD 12,276, 13,210, 6,974, 9,421/QALY, respectively. Compared with nedaplatin or SC followed by tislelizumab, the ICERs of CAD were USD 4,183, 2,804/QALY; CAD was dominant compared with nedaplatin or SC followed by nivolumab; The ICER of sugemalimab + SC followed by docetaxel and PED were USD 522,023, 481,639/QALY compared with CAD. Pembrolizumab + SC and camrelizumab + SC were the most effective and cost-effective first-line options, respectively; tislelizumab was the most effective and cost-effective second-line therapy. Tislelizumab used in second-line was more effective than first-line, no significant differences between their cost-effectiveness. Sensitivity and scenario analysis confirmed robustness of the results. PED and CAD are the most effective and cost-effective treatment sequence, respectively; pembrolizumab + SC and camrelizumab + SC are the most effective and cost-effective first-line choice, respectively; tislelizumab is the most effective and cost-effective second-line choice.

Multistate Pharmacometric Model to Define the Impact of Second-Line Immunotherapies on the Survival Outcome of the IMpower131 Study.

Overall survival is defined as the time since randomization into the clinical trial to event of death or censor (end of trial or follow-up), and is considered to be the most reliable cancer end point. However, the introduction of second-line treatment after disease progression could influence survival and be considered a confounding factor. The aim of the current study was to set up a multistate model framework, using data from the IMpower131 study, to investigate the influence of second-line immunotherapies on overall survival analysis. The model adequately described the transitions between different states in patients with advanced squamous non-small cell lung cancer treated with or without atezolizumab plus nab-paclitaxel and carboplatin, and characterized the survival data. High PD-L1 expression at baseline was associated with a decreased hazard of progression, while the presence of liver metastasis at baseline was indicative of a high risk of disease progression after initial response. The hazard of death after progression was lower for participants who had longer treatment response, i.e., longer time to progression. The simulations based on the final multistate model showed that the addition of atezolizumab to the nab-paclitaxel and carboplatin regimen had significant improvement in the patients' survival (hazard ratio=0.75, 95% prediction interval: 0.61-0.90 favoring the atezolizumab + nab-paclitaxel and carboplatin arm). The developed modeling approach can be applied to other cancer types and therapies to provide a better understanding of efficacy of drug and characterizing different states, and investigate the benefit of primary therapy in survival while accounting for the switch to alternative treatment in the case of disease progression.

86P Efficacy and safety of IBI110 (anti-LAG-3 mAb) in combination with sintilimab (anti-PD-1 mAb) in advanced squamous non-small cell lung cancer (sqNSCLC): Updated results of the phase Ib study

Although PD-1/L1 inhibitors have shown efficacy in advanced/metastatic sqNSCLC, many patients (pts) do not achieve robust response or durable benefit to this treatment. Hence, novel therapies that meet this requirement are needed. The preliminary results of IBI110 combined with sintilimab and chemotherapy (paclitaxel plus carboplatin, TP) (combination therapy) in pts with treatment-naive sqNSCLC were previously presented (Caicun Zhou et al. ASCO 2022). Here, we report updated results of this phase Ib study.

132P Randomized phase III study of tislelizumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced squamous non-small cell lung cancer (sq-NSCLC): RATIONALE-307 updated analysis

Interim analysis of the open-label phase 3 RATIONALE-307 study (NCT03594747) demonstrated clinical benefit, including significantly improved progression-free survival (PFS) with a manageable safety profile, of tislelizumab (TIS) plus chemotherapy (chemo) as first-line (1L) therapy in patients (pts) with advanced sq-NSCLC vs chemo alone. Here, we report updated results.

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.

1092P Clinical potential of circulating tumor DNA (ctDNA)-based molecular response (MR) and baseline blood-based tumor mutational burden (bTMB) for monitoring response to first-line (1L) chemoimmunotherapy in advanced squamous non-small cell lung cancer (sqNSCLC)

The clinical utility of ctDNA-based approaches, such as bTMB and MR, to monitor and predict response during chemo-immunotherapy was evaluated using longitudinal cohort samples from a phase IIa study of patients (pts) with advanced sqNSCLC treated with 1L avelumab in combination with cetuximab and chemotherapy (NCT03717155). Fifty-two plasma samples were obtained from 21 pts treated with 1L avelumab, cetuximab, gemcitabine, and cisplatin for 4 x 3-week cycles followed by avelumab and cetuximab maintenance. The confirmed best overall response (BOR) per RECIST v1.1 was available for 19 pts. The GuardantOMNI liquid biopsy (LBx) assay was used to detect somatic alterations in 497 genes and generate bTMB from baseline, and MR scores from baseline and day 85. bTMB and somatic alterations influencing response were explored. MR scores were calculated using the validated Guardant Response algorithm. Associations between ctDNA metrics and BOR were assessed. We detected somatic mutations in 51 of 52 samples. Biomarker-positive pts were defined as those with high bTMB score (≥20 mut/Mb) and/or STK11, KEAP1, LRP1B, ARID1A/1B/2 mutations. Ten of 18 baseline samples were biomarker-positive; all biomarker-positive pts had a BOR of partial response (PR) or stable disease (SD) and no progressive disease (PD). Eight of 18 baseline samples were biomarker-negative, of which 5 had a BOR of PR or SD and 3 had PD. All 3 pts with PD were TMB-low and 1 had a dual STK11/KRAS alteration, which was previously shown to negatively affect the clinical benefit of immunotherapy. The average ctDNA reduction at the tumor assessment visit following day 85 LBx collection for pts with PR/SD was significantly greater than for pts with PD (82% vs 57%; P=.032). We showed that plasma ctDNA analysis supported MR assessment in pts treated with avelumab combination therapy, which could indicate its clinical utility as an adjunct to RECIST in monitoring tumor response. Plasma TMB-high combined with defined somatic mutations was associated with avelumab combination benefit. Prof. F. Ciardiello and Dr. Z. Feng are acknowledged as first authors and equal contributors to this abstract.

1160P Survival impact of second-line immune checkpoint inhibitors in the elderly patients with advanced squamous non-small cell lung cancer: Post-hoc analysis from a CAPITAL study

The CAPITAL study, a randomized phase III trial, was conducted to compare carboplatin and nab-paclitaxel (nab-P/C) with docetaxel (D) for treating elderly patients with squamous-cell lung cancer. We performed a safety analysis for patients ≥75 and <75 years old from each treatment group, post-hoc analysis of the impact of second-line immune checkpoint inhibitors (ICI) on survival, and intra-cycle nab-paclitaxel skip status. The common adverse events (AEs) in the nab-P/C group were leucopenia, neutropenia, and anemia, while leucopenia, neutropenia, and febrile neutropenia were common in the D group. In the D group, there was a high frequency of AEs, particularly neutropenia for patients ≥75. In the nab-P/C group, the common AEs were anemia and thrombocytopenia for those patients. Thirty-eight percent (74/190) of the patients were transferred to the second-line ICI treatment, 36 and 38 patients from the nab-P/C and D groups, respectively. The overall survival of patients on ICI depended on their reason for discontinuing the first treatment. In both groups, improvement of overall survival was observed in patients with disease progression after first-line therapy. Median overall survival after discontinuation of nab-P/C was 321 d with ICI and 142 d without ICI; in the D group, it was 311 d with ICI and 256 d without ICI. However, no survival benefit was seen in patients who discontinued due to AEs. Their median overall survival after discontinuing nab-P/C was 224 d with ICI and 373 d without ICI; after discontinuing D, the median overall survival was 186.5 d with ICI and 154 d without ICI. In cycle one and two, 10%–30% of patients skipped taking nab-paclitaxel, and over 50% skipped taking it after cycle 3. Nab-P/C improved overall survival more than D in elderly patients with advanced or recurrent squamous cell lung cancer. ICI treatment did not improve the overall survival of patients in both groups, who discontinued the first line treatment due to AEs. Nab-P/C did not show a significant increase in toxicity in patients over 75 y of age. Many patients skipped nab-paclitaxel within cycles.