Non-squamous Non-small Cell Lung Cancer Research Articles

Characterization of renal injury in non-squamous non-small cell lung cancer patients treated with pemetrexed: A single-center retrospective study.

Pemetrexed is a key therapeutic agent for advanced non-squamous non-small cell lung cancer (Nsq-NSCLC), yet it is associated with renal toxicity. This study aims to elucidate the incidence, risk factors, and survival impact of renal injury in patients with Nsq-NSCLC treated with pemetrexed. We conducted a retrospective study including 136 patients with Nsq-NSCLC treated with pemetrexed. Data on demographics, renal function, progression-free survival (PFS), and overall survival (OS) were collected. Renal injury was defined as a reduction above 25% in estimated glomerular filtration rate (eGFR) from baseline. Its associated risk factors were analyzed using logistic regression, and impact on survival was analyzed using log-rank test. The creatinine clearance rate (CCr) was calculated, and a CCr < 45 mL/min served as a contraindication for continuing pemetrexed. The study found a 31.6% (43/136) incidence of renal injury, with 9.6% (13/136) having CCr < 45 mL/min and discontinuing pemetrexed. Univariate and multivariate analyses identified factors significantly associated with increased renal injury risk including older age, use of cisplatin, and higher number of pemetrexed cycles. The patients with renal injury had a median PFS (mPFS) of 13.5 months and a median OS (mOS) of 36.0 months, while the patients without had an mPFS of 9.0 months and an mOS of 35.0 months, and these differences were not statistically significant. Renal injury is a considerable complication in patients with Nsq-NSCLC undergoing pemetrexed treatment, with age, platinum type, and pemetrexed treatment cycles as key risk factors. These findings highlight the necessity for careful renal monitoring in this patient population.

TROPION-Lung07: Phase III study of Dato-DXd+pembrolizumab±platinum-based chemotherapy as 1L therapy for advanced non-small-cell lung cancer.

For patients with advanced/metastatic non-small-cell lung cancer (NSCLC) without actionable genomic alterations and low (<50%) PD-L1 expression, pembrolizumab plus pemetrexed and platinum chemotherapy is a preferred first-line treatment. These patients have comparatively worse outcomes than those with higher PD-L1 expression, underscoring the need for new combination strategies. Datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate, has demonstrated encouraging antitumor activity and safety in this patient population. We describe the rationale and design of TROPION-Lung07, a randomized, open-label Phase III study assessing Dato-DXd in combination with pembrolizumab with/without platinum-based chemotherapy versus pembrolizumab plus pemetrexed and platinum-based chemotherapy in patients with advanced/metastatic non-squamous NSCLC without actionable genomic alterations and <50% PD-L1 expression. Primary study objectives are progression-free survival and overall survival.Clinical Trial Registration: NCT05555732 (ClinicalTrials.gov).

Osimertinib (Tagrisso)

Canada’s Drug Agency (CDA-AMC) recommends that Tagrisso in combination with pemetrexed and platinum-based chemotherapy should be reimbursed by public drug plans for the first-line treatment of patients with locally advanced (not amenable to curative therapies) or metastatic non–small cell lung cancer (NSCLC) which harbours epidermal growth factor receptor (EGFR) exon 19 deletions (Ex19del) or exon 21 (L858R) substitution mutations if certain conditions are met. Tagrisso plus chemotherapy should only be covered to treat adult patients (aged ≥ 18 years) who have nonsquamous NSCLC; whose tumours have spread to other parts of the body, returned after treatment, or cannot be removed by surgery or radiation; whose tumours harbour EGFR Ex19del or L858R substitution mutations; and who are in relatively good health. Tagrisso should not be covered to treat patients who have a history of breathing difficulties caused by scarring and inflammation in the lung tissue; who have a history of heart problems associated with their heart taking longer to recharge between beats or their heart beating too fast, too slow, or in an irregular way; or, who have already been treated for NSCLC with treatments affecting their entire body (except for treatments given at least 6 months before the tumour returned, as a first step to shrink a tumour before the primary treatment, or as an additional treatment after the primary treatment to lower the risk of the tumour returning). Tagrisso should only be reimbursed if it is prescribed in combination with pemetrexed and platinum-based (i.e., cisplatin or carboplatin) chemotherapy by clinicians with expertise in treating NSCLC, and the cost of Tagrisso is reduced. Reimbursement of Tagrisso plus chemotherapy should be discontinued if a patient’s cancer grows or spreads, or if treatment is unacceptably toxic to the patient.

Sintilimab plus chemotherapy with or without bevacizumab biosimilar IBI305 in EGFR-mutated non-squamous NSCLC patients who progressed on EGFR TKI therapy: A China-based cost-effectiveness analysis.

This study aims to compare the cost-effectiveness of sintilimab in combination with chemotherapy, with or without bevacizumab biosimilar IBI305, versus chemotherapy alone for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) who have progressed on tyrosine-kinase inhibitor (TKI) treatment from the perspective of the Chinese healthcare system. 10-year Markov model was developed using a 21-day cycle length. Transition probabilities were derived from the ORIENT-31 trial, while cost and health state utilities were obtained from publicly databases, local hospitals, and published literature. Incremental cost-effectiveness ratios (ICERs) were calculated as the primary model output and compared to a willingness-to-pay (WTP) threshold range of $15,289.34 to $38,223.34 per quality-adjusted life-years (QALY). Sensitivity analyses were performed to assess the robustness of the model. In the base-case analysis, sintilimab plus IBI305 and chemotherapy had an ICER of $53,266.32/QALYs, exceeding the upper WTP threshold. Sintilimab plus chemotherapy had an ICER of $15,329.11/QALY, slightly above the lower WTP threshold. Subgroup analysis yielded consistent results. Deterministic sensitivity analyses found no ICER for sintilimab plus chemotherapy beyond the upper WTP threshold. Most model input changes did not decrease the ICER of sintilimab plus IBI305 and chemotherapy below the upper WTP threshold. Probabilistic sensitivity analyses further demonstrated the cost-effectiveness superiority of sintilimab plus chemotherapy over sintilimab plus IBI305 and chemotherapy. This study supports the cost-effectiveness of using sintilimab in combination with chemotherapy. Nevertheless, the cost-effectiveness of combining sintilimab with IBI305 and chemotherapy in this particular patient group may be lacking.

P4.11D.10 A Phase II Trial of Tiragolumab with Carboplatin, Pemetrexed, And Atezolizumab in Non-Squamous NSCLC and Brain Metastases

P4.11D.10 A Phase II Trial of Tiragolumab with Carboplatin, Pemetrexed, And Atezolizumab in Non-Squamous NSCLC and Brain Metastases

OA16.03 Telisotuzumab Vedotin in Asian Patients with C-Met Protein-Overexpressing Non-Squamous EGFR WT NSCLC: Results from LUMINOSITY

OA16.03 Telisotuzumab Vedotin in Asian Patients with C-Met Protein-Overexpressing Non-Squamous EGFR WT NSCLC: Results from LUMINOSITY

P2.10A.04 Valemetostat and Datopotamab Deruxtecan in Previously Treated, Advanced, Unresectable, or Metastatic Non-squamous NSCLC

P2.10A.04 Valemetostat and Datopotamab Deruxtecan in Previously Treated, Advanced, Unresectable, or Metastatic Non-squamous NSCLC

MA11.07 Pembrolizumab Plus Maintenance Olaparib as First-Line Therapy for Metastatic Nonsquamous NSCLC: Phase 3 KEYLYNK-006 Study

MA11.07 Pembrolizumab Plus Maintenance Olaparib as First-Line Therapy for Metastatic Nonsquamous NSCLC: Phase 3 KEYLYNK-006 Study

Comparative efficacy of chemo-immunotherapy combination regimens in the frontline setting for NSCLC based on reconstructed patient data

Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of metastatic NSCLC and have become standard first-line therapy both as monotherapy, for patients with PD-L1 expression ≥50%, and in combination with chemotherapy (CT), regardless of PD-L1 expression. This study used an artificial intelligence technique, the IPDfromKM method, to reconstruct individual patient data from Kaplan-Meier curves of phase III randomised clinical trial results to provide a comparative overview of different first-line chemo-immunotherapy options. Overall survival (OS) was estimated using hazard ratios and restricted mean survival time (RMST). Ten clinical trials were included in the analysis. In the squamous population, combinations of cemiplimab + CT (HR = 0.56), pembrolizumab + CT (HR = 0.67), and nivolumab + ipilimumab + CT (HR = 0.71) significantly improved OS compared with CT alone, with no difference between treatments. At longer follow-up, nivolumab + ipilimumab + CT showed longer RMST compared to pembrolizumab + CT in the PD-L1 < 1% subgroup (24.9 months vs. 22.8 months). In non-squamous NSCLC, the survival benefit of ICIs + CT was much more homogeneous, with similar results across the different options. Overall, pembrolizumab + CT showed the best results both in terms of HR (0.68, 95%CI 0.60-0.77) and RMST at long follow-up (30.4 months in the PDL-1 ≥ 1% subgroup and 24 months in the PDL-1 < 1% population). In conclusion, there are some differences between frontline options for treating metastatic NSCLC based on tumour histology and PD-L1 expression. However, further head-to-head trials and longer follow-up are needed to clarify the clinical impact of these differences.

Budget impact analysis of pembrolizumab versus the novel PD-1 inhibitor toripalimab in locally advanced or metastatic nonsquamous non-small cell lung cancer

ABSTRACT Aim To estimate the budget impact of adding a toripalimab regimen to the existing treatment mix of pembrolizumab, both with pemetrexed and carboplatin, in patients with locally advanced or metastatic nonsquamous NSCLC within two price inputs (wholesale acquisition cost (WAC) and average sales price (ASP)). Methods Budget impact analysis comparing a treatment mix “without” versus “with” the toripalimab regimen in the annual US nonsquamous NSCLC population treated with a PD-1 inhibitor, a 3-year time horizon, toripalimab market share of 1% in 2024, increasing to 4% (2025) and 5% (2026), and medication use adjustments for discontinuation or progression to estimate fully-treated-patient-equivalents. Cost inputs included drugs, administration, and grade 3/4 adverse event (AE) management. The models were replicated in a 1-million-member plan to estimate costs per-member-per-month (PMPM) and per-member-per-year (PMPY). One-way (OWSA) and probabilistic sensitivity analyses (PSA) as well as two scenario analyses were performed. Results In the “without” scenario, the 3-year WAC costs for the pembrolizumab regimen total $40,750,234,637 ($39,024,548,745 for treatment and $1,725,685,894 for managing AEs). In the “with” scenario, these costs decline to $39,341,379,081. Corresponding “with” costs for toripalimab are $1,186,027,704 (treatment) and $99,454,471 (AE management) for a total of $1,285,482,175. This yields annual net savings of between $10,779,362 (at 1% market share) in 2024 and $64,858,298 (5% market share) in 2026, for 3-year savings of $123,373,381. The associated savings in a 1-million-member plan are $0.030 PMPM and $0.363 PMPY. The ASP model shows similar patterns. Savings were demonstrated in 68% of PSA simulations; OWSAs and scenario analyses reveal how parameter variability impacts results. Conclusion Significant savings are likely achievable from treating between 1% (year 1) to 5% (year 3) of nonsquamous NSCLC patients with the toripalimab regimen. Projected 3-year savings range from $122 million (ASP) to $123 million (WAC); corresponding to savings of $0.030 PMPM and $0.363 PMPY.

Impact of EGFR Mutation on Prognosis of Stage IV Non-Squamous Non-Small Cell Lung Cancer NSCLC: A Retrospective Analysis

Impact of EGFR Mutation on Prognosis of Stage IV Non-Squamous Non-Small Cell Lung Cancer NSCLC: A Retrospective Analysis

P4.07F.05 Low OLFM1/BMP6 Expression Identifies High-Risk Stage I Non-Squamous Non-Small Cell Lung Cancer after Pulmonary Resection

P4.07F.05 Low OLFM1/BMP6 Expression Identifies High-Risk Stage I Non-Squamous Non-Small Cell Lung Cancer after Pulmonary Resection

P4.11E.02 Efficacy of Pembrolizumab Plus Pemetrexed in Older Patients with Non-squamous NSCLC According to PD-L1 Status from the CJLSG1901 Study

P4.11E.02 Efficacy of Pembrolizumab Plus Pemetrexed in Older Patients with Non-squamous NSCLC According to PD-L1 Status from the CJLSG1901 Study

Real-world clinical outcomes among patients with non-squamous advanced non-small cell lung cancer (aNSCLC) treated with docetaxel-based regimens post initial standard of care (SOC) in the United States.

392 Background: Immunotherapy (IO) or targeted therapy used separately or in combination with platinum-based chemotherapy (PBC) are SOC among treatment naïve aNSCLC patients. After progression on SOC, patients have limited treatment options. Previous US-based real-world studies have shown docetaxel ± ramucirumab as the most used line of treatment (LOT) post-SOC. This study sought to assess clinical outcomes associated with docetaxel+ramucirumab (DTX-R) or docetaxel monotherapy (DTX) received post SOC among patients with non-squamous aNSCLC independent of genomic alteration status. Methods: This retrospective study, using electronic medical record data from the ConcertAI Patient360 NSCLC data product (01/2015–09/2022), included adult patients (≥18 years) with stage IIIB-IV non-squamous aNSCLC who received docetaxel-based regimens (DTX-R or DTX) as subsequent LOT (index LOT) after discontinuation of the prior qualifying SOC LOT (IO + PBC or targeted therapy + PBC). Kaplan-Meier analysis was used to estimate median time to discontinuation (TTD), time to next treatment (TTNT), real-world progression-free survival (rwPFS), and real-world overall survival (rwOS) on docetaxel-based index regimens. Results: Out of 656 non-squamous aNSCLC patients which discontinued prior SOC therapy, 165 (25.2%) received a docetaxel-based regimen (n = 96 [DTX-R]; 69 [DTX]) which was the most commonly received index regimen. Other patients received a variety of other treatments, most commonly, pembrolizumab monotherapy (11.4%), pemetrexed + pembrolizumab (8.4%), pemetrexed monotherapy (4.4%), carboplatin + pemetrexed (4.1%), and osimertinib (3.8%). Among patients with index DTX-R and DTX, median age was 66 and 65 years; 36.5% and 60.9% were female; 74.0% and 63.8% were White; 86.5% and 75.4% received care in community setting; 15.1% and 31.8% had brain metastasis; 63.6% and 65.2% had ECOG 0-1; 1 and 2 median prior LOT; and median follow-up from index was 10 and 11 months, respectively. Median TTD, TTNT, rwPFS, and rwOS for docetaxel-based regimens are reported in the table. Conclusions: Docetaxel ± ramucirumab is the most used regimen in a fragmented treatment landscape post SOC therapy among patients with non-squamous aNSCLC. Observed rwOS, rwPFS, and treatment durations on docetaxel-based regimens in this real-world setting suggested the limited clinical benefit associated with these therapies. Overall, there is a need for more effective treatment options post SOC therapies. Real-world outcomes for DTX-R and DTX treated patients post SOC. Outcome, months (median, 95% CI) Docetaxel+Ramucirumab Docetaxel Monotherapy rwOS 6.37 (4.4, 9.3) 4.73 (2.3, 7.8) rwPFS 3.88 (2.8, 6.0) 3.22 (2.0, 5.7) TTD 3.06 (2.4, 3.5) 1.71 (1.7, 2.4) TTNT 3.45 (2.9, 4.5) 3.02 (1.9, 4.6)

EP.12H.09 Phase 1b/2a Study of ATR Inhibitor Tuvusertib + Anti-PD-1 Cemiplimab in Patients with Advanced Non-Squamous NSCLC

EP.12H.09 Phase 1b/2a Study of ATR Inhibitor Tuvusertib + Anti-PD-1 Cemiplimab in Patients with Advanced Non-Squamous NSCLC

P42-5 Efficacy and safety of camrelizumab and carboplatin and pemetrexed in advanced nonsquamous NSCLC: A systematic review

P42-5 Efficacy and safety of camrelizumab and carboplatin and pemetrexed in advanced nonsquamous NSCLC: A systematic review

OA11.05 Results of a Phase III Trial of Prolgolimab with Chemotherapy as First-Line Therapy for Patients with Advanced Non-Squamous NSCLC: DOMAJOR

OA11.05 Results of a Phase III Trial of Prolgolimab with Chemotherapy as First-Line Therapy for Patients with Advanced Non-Squamous NSCLC: DOMAJOR

OA08.05 Tusamitamab Ravtansine vs Docetaxel in Previously Treated Advanced Nonsquamous NSCLC: Results from Phase 3 CARMEN-LC03 Trial

OA08.05 Tusamitamab Ravtansine vs Docetaxel in Previously Treated Advanced Nonsquamous NSCLC: Results from Phase 3 CARMEN-LC03 Trial

EP.06G.13 TP53 Somatic Mutation and its Association with Clinicopathological Parameters and Long-Term Clinical Outcome in Non-Squamous NSCLC Patients

EP.06G.13 TP53 Somatic Mutation and its Association with Clinicopathological Parameters and Long-Term Clinical Outcome in Non-Squamous NSCLC Patients

P2.10B.01 Exploratory Analyses of Tusamitamab Ravtansine vs Docetaxel in Previously Treated Non-squamous NSCLC Patients: CARMEN-LC03

P2.10B.01 Exploratory Analyses of Tusamitamab Ravtansine vs Docetaxel in Previously Treated Non-squamous NSCLC Patients: CARMEN-LC03