Treatment Of Metastatic Cancer Research Articles

Evolution of therapy for ALK-positive lung carcinomas: Application of third-generation ALK inhibitors in real clinical practice

Lung cancer is currently a heterogeneous group of diseases, whose heterogeneity is determined not only by its phenotypic, but also by its genetic profile. A special place is occupied by subtypes that have driver mutations. Due to new antitumor agents – small molecule inhibitors – it has become possible to significantly increase patients’ chances of survival. The diagnostic panel most often includes mutations in the EGFR, ALK, ROS1, BRAF genes; somewhat less frequently, genetic changes in MET, KRAS, HER2, NTRK, etc. are determined. This distribution is most likely explained by the availability of appropriate inhibitors. The article provides an overview of different generations of ALK inhibitors known in the Russian Federation, among them the most famous: crizotinib, ceritinib, alectinib and lorlatinib. These drugs are included in the clinical guidelines for the treatment of ALK-positive lung carcinomas of all major oncology societies. The article describes the results of registration studies proving the advantage of ALK inhibitors over standard therapy, including the results of the CROWN study. In this study, the latest generation of ALK inhibitors, lorlatinib, demonstrates superiority over crizotinib, with a 73% reduction in the risk of progression or death and better intracranial response rates. A description of a clinical case of treatment of metastatic lung cancer using the third generation ALK inhibitor lorlatinib is provided. The drug was prescribed in the first line of therapy. The patient’s treatment outcome indicates high efficacy of lorlatinib in the first-line treatment of ALK translocation-positive lung cancer, along with low toxicity. The treatment period has already been more than 70 months and the patient continues therapy at the time of the last control. A complete response to lorlatinib therapy was recorded. During treatment, the following adverse events were recorded: hypertriglyceridemia, grade 1 toxicity, hypercholesterolemia, grade 2 toxicity, increased liver transaminases, grade 1 toxicity.

Minimally invasive stabilization using screws and cement for acetabular metastatic tumor: a case report

BackgroundThe aim of this case report is to evaluate minimally invasive stabilization using screws and cement for acetabular metastatic tumor and summarize the indications and contraindications for minimally invasive stabilization of acetabular metastatic tumors with screw and cement techniques.Case presentationUnder imaging guidance, a patient with acetabular metastatic tumor was treated with hollow screw combined with bone cement fixation. Ischial screw, ascending branch screw, and anterior and posterior screws were inserted to firmly fix the anterior and posterior column of the acetabulum. At the same time, the third screw connected the anterior and posterior columns together, combined with bone cement into the fracture site to further increase local stability and resist bone defects caused by local tumor osteolysis. The patient was a 52-year-old Uygur male. Herein, we summarize his clinical symptoms and operation. Differences in visual analog scale and walking function (Musculoskeletal Tumor Society) before operation and at 2 months, 6 months, and 12 months after operation were compared.ResultsPostoperative complications and tumor progression were recorded. The patient was followed up for 16 months, and the operative time was 60 minutes. In total, 20 ml of bone cement was injected into the acetabular posterior column and the top of the acetabulum. VIsual analog scale score was 8 before operation, 3 at 2 months, 3 at 6 months, and 2 at 12 months after operation. Musculoskeletal Tumor Society function was 13 before operation, 23 at 2 months, 25 at 6 months, and 26 at 12 months after operation. During follow-up, no cement leakage, fever, hip nerve injury, pulmonary embolism, or imaging findings of further destruction of the acetabulum and surrounding bone were noted.ConclusionThis case report shows that the treatment of acetabular metastatic cancer with minimally invasive stabilization using screws and cement under the C arm can effectively relieve pain and enhance the strength of the pelvis, and is innovative and feasible.

Ornidazole Inhibits the Angiogenesis and Migration Abilities of Non-small Cell Lung Cancer (NSCLC) via Downregulation of VEGFA/VEGFR2/NRP-1 and PI3K/AKT/mTOR Pathways.

Around the world, non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths among all cancers. Despite advancements in new therapeutic approaches over the past few decades, the five-year survival rate still remains disappointing. The lack of effective anti-angiogenic and anti-migration drugs is the biggest obstacle to the treatment of metastatic lung cancer. Therefore, there is a need to develop new and effective therapeutic compounds targeting anti-angiogenic and anti-migration pathways for the treatment of lung cancer. Ornidazole is a nitroimidazole agent widely used in the treatment of parasitic infections such as trichomonas vaginalis, amebiasis and giardiasis. This study aimed to investigate the anti-proliferative, anti-angiogenic and anti-mitotic activities of the anti-parasitic drug Ornidazole in two human lung cancer cell lines (A549, H1299). We determined the effects of Ornidazole, on cell viability, apoptosis, migration, angiogenesis and metastatic ability against NSCLC in lung cancer cell lines. Its action on the mRNA and protein expression levels of VEGFA, VEGFR2, NRP1, Casp9, Casp3, Bax, Bcl-2, PIK3CA, AKT, MTOR, PTEN and FOX3A was assessed. Furthermore, in this study the effects on cell migration, cell viability and proliferation was evaluated through wound healing, MTT and Crystal violet assays. This study demonstrated that Ornidazole effectively reduces cell viability and migration ability, inhibits angiogenesis and metastatic abilities in NSCLC cells. In conclusion, these results may shed light on the treatment of NSCLC, and we suggest the anti-parasitic drug Ornidazole as a new agent with potential anti-angiogenic and anti-mitotic activity by interfering with the molecular pathways that trigger tumor angiogenesis and migration.

CO147 The Potential Long-Term Comparative Effectiveness of Larotrectinib Vs. Entrectinib for Treatment of Metastatic Fusion-Positive Cancers in Children and Young Adults

CO147 The Potential Long-Term Comparative Effectiveness of Larotrectinib Vs. Entrectinib for Treatment of Metastatic Fusion-Positive Cancers in Children and Young Adults

CO43 A Systematic Literature Review of Comparative Efficacy Measures in Randomized Controlled Trials of Darolutamide Treatment in Metastatic Hormone-Sensitive Prostate Cancer

CO43 A Systematic Literature Review of Comparative Efficacy Measures in Randomized Controlled Trials of Darolutamide Treatment in Metastatic Hormone-Sensitive Prostate Cancer

Lutetium-177 on ambulatory basis, a radiation safety approach

The overarching objective of the study is to assess the applicability of 177Lu-PSMA-617 for the treatment of metastatic castration-resistant prostate cancer and 177Lu-DOTATATE for neuroendocrine tumors in an ambulatory context. To this end, the study determines the effective half-life of these two commercial versions of the isotope during the first 24 h of treatment. These measurements are then used to estimate the external dose absorbed by caregivers and the amount of 177Lu to be discharged into the sewage network in the case of ambulatory treatment. The study utilized live dosimetry measurements of 18 hospitalized patients during 24 h. The detector was placed above the bed and the data was collected every 5 min. Data was processed, visualized, and analyzed using several Python libraries. 177Lu-PSMA and 177Lu-DOTATATE average effective half-life during hospitalization was 6.42 ± 0.14 h and 4.25 ± 0.09 h, respectively. Predicted external dose for caregivers was estimated to be less than 0.1 mSv/cycle. Around 0.45 GBq of 177Lu would be discharged into the sewage network in case of 177Lu-DOTATATE and 0.3 GBq in case of 177Lu-PSMA. From a radiological safety point of view, it is safe to treat with 177Lu on an ambulatory basis. However, in future studies, the amount of 177Lu discharged into wastewater should be considered.

Enhanced abscopal anti-tumor response via a triple combination of thermal ablation, IL-21, and PD-1 inhibition therapy

Despite the success of immune checkpoint inhibitors (ICIs) in treating solid tumors, lots of patients remain unresponsive to this therapy. Microwave ablation (MWA) stimulates systemic adaptive immunity against tumor cells by releasing tumor antigens. Additionally, IL-21 has demonstrated importance in stimulating T-cell effector function. The combination of these three therapies—MWA, IL-21, and anti-PD-1 monoclonal antibodies (mAbs)—has yet to be explored in the context of cancer treatment.In this study, we explored the impact of thermal ablation on IL-21R expression in tumor-infiltrating lymphocytes (TILs). Subsequently, we assessed alterations in the tumor microenvironment (TME) and peripheral lymphoid organs. Additionally, we conducted a thorough examination of tumor-infiltrating CD45+ immune cells across various treatment groups using single-cell RNA sequencing (scRNA-seq). Moreover, we determined the potential anti-tumor effects of the triple combination involving MWA, IL-21, and anti-PD-1 mAbs.Our findings revealed that MWA upregulated the expression of IL-21R on various immune cells in the untreated tumors. The combination of MWA with IL-21 exhibited a robust abscopal anti-tumor effect, enhancing the effector function of CD8+ T cells and facilitating dendritic cells' maturation and antigen presentation in the untreated tumor. Notably, the observed abscopal anti-tumor effect resulting from the combination is contingent upon T-cell recirculation, indicating the reliance of systemic adaptive immunity for this treatment regimen. Additionally, the combination of MWA, IL-21, and PD-1 mAbs demonstrated profound abscopal anti-tumor efficacy. Our findings provide support for further clinical investigation into a triple combination therapy involving MWA, IL-21, and ICIs for the treatment of metastatic cancer.

Unlocking the Next Frontier in Precision Oncology: Addressing Drug-Tolerant Residual Disease.

Drug-tolerant residual disease (DTRD) after the initial maximal response to a systemic therapy can serve as a tumor reservoir for the development of acquired drug resistance and represents a major clinical challenge across various cancers and types of therapies. To unlock the next frontier in precision oncology, we propose a fundamental paradigm shift in the treatment of metastatic cancers with a sharpened focus towards defining, monitoring, and therapeutically targeting the DTRD state.

A phase I/II open label study to assess safety and preliminary evidence of a therapeutic effect of azeliragon in patients refractory to first-line treatment of metastatic pancreatic cancer.

TPS4212 Background: Azeliragon is an orally administered small molecule, administered once daily, that inhibits RAGE interactions with its natural ligands, including HMGB1 and S100 proteins. Azeliragon was previously under development for Alzheimer’s disease and failed to show efficacy in phase 3 trials. Clinical safety data from these trials, with over 1500 individuals dosed for periods up to 18 months, indicated that azeliragon has a high level of safety and tolerability, virtually indistinguishable from placebo. RAGE, the receptor for advanced glycation end products, is highly expressed in pancreatic ductal adenocarcinoma (PDAC). RAGE interaction with its ligands, including S100 proteins and HMGB1 released from PDAC cells, promotes PDAC invasion, metastasis, and resistance to 5 FU and Gemcitabine. PDAC-secreted S100 proteins can also stimulate fibroblasts surrounding PDAC cells since RAGE is positively expressed in fibroblasts, promoting the desmoplastic response. RAGE has also been implicated in the muscle wasting associated with cancer and with aging, as well as in neuropathic pain, suggesting a potential supportive role in PDAC treatment. Methods: This is an open label study to determine the safety and preliminary evidence of a therapeutic effect of azeliragon in patients refractory to the standard of care treatment of metastatic pancreatic cancer. Azeliragon is administered at three dose levels in a rolling dose escalation strategy with 6 patients at each dose level: 5 mg/day (level 1), 10 mg/day (level 2) and 20 mg/day (level 3). These dose levels have an initial loading dose for 6 days at 15 mg daily, 15 mg twice a day and 30 mg twice a day, respectively. The primary objective is to determine the RP2D, defined as the dose for which <33% patients experience a dose limiting toxicity (DLT) within 28 days from initiation of dosing. Secondary endpoints include disease control, overall survival, changes in pain as determined by the Brief Pain Inventory, and changes in ECOG performance status, weight, and serum albumin. The study received regulatory approval and accrual started in June 2023. Clinical trial information: NCT05766748 .

Prognostic analysis of PD-1/CTLA-4 bispecific antibody combined with chemotherapy first-line treatment for recurrent or metastatic cervical cancer: A multicenter real-world study.

e17520 Background: PD-1/CTLA-4 bispecific antibody, cadonilimab, has shown excellent efficacy in advanced cervical cancer patients who have previously received platinum containing chemotherapy. However, its effectiveness in first-line treatment remains unclear yet. This study aims to evaluate the efficacy, safety, and prognostic biomarker of cadonilimab combined with chemotherapy for the first line treatment of recurrent or metastatic cervical cancer. Methods: Information on patients with recurrent or metastatic cervical cancer who received chemotherapy combined with cadonilimab as first-line treatment at three cancer centers from July 2022 to September 2023 were collected. Patients have not received systemic chemotherapy previously and are not suitable for curative local treatment, received cadonilimab 10mg/kg Q3W for up to 17 cycles + chemotherapy for up to 6 cycles (paclitaxel 135-175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5), ± bevacizumab 10-15 mg/kg. Clinical outcomes were analyzed using the Kaplan–Meier method with log-rank test. RNA-seq was used to analyze differential expressed genes (DEGs) between PR+CR group and PD+SD group. Results: There are 52 patients enrolled, median age 56.5 years (39–87 years). The median follow-up time was 12 months (5–23 months). There were 29 cases of lung metastasis, 7 cases of liver metastasis, 11 cases of bone metastasis, 12 cases of pelvic metastasis, and 11 cases of lymph node metastasis. The median number of cycles of cadonilimab and chemotherapy were 8 and 5, respectively. The 1-year overall survival (OS) and progression-free survival (PFS) rates were 91% and 72.5%, respectively. The objective response rate (ORR) was 75%.The expression of PD-L1 and bevacizumab had no effect on prognosis. The most common treatment-related adverse events (TRAEs) were neutropenia (78.2%), anemia (82.7%), thrombocytopenia (51.9%), thyroid dysfunction (50%), nausea and vomiting (88.5%), fatigue (71.2%). Grade 3 or 4 adverse events (AE) were reported in 36.5% patients, mainly hematological toxicity. The most significant differential pathways between PR+CR group and PD+SD group were adhesion, Hippo signaling pathway, NOD like receptor signaling pathway, programmed cell death, and secretory granules. Conclusions: Cadonilimab combined with chemotherapy ± bevacizumab as first-line treatment for recurrent or metastatic cervical cancer was effective and well-tolerant.

Non-receipt of targeted and immunotherapies in diverse patients with metastatic cancers.

e13563 Background: The rapid evolution of molecularly targeted kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in the treatment of metastatic cancer, coupled with high drug costs, raises potential for unwarranted variation in patient management. We evaluated correlates of non-receipt of TKIs and ICIs in a diverse, population-based sample of patients with metastatic non-small cell lung cancer (NSCLC), kidney and bladder (GU) cancer, and melanoma. Methods: We identified 2240 patients diagnosed in 2019 with metastatic NSCLC, GU cancer, or melanoma and reported to the Georgia or Los Angeles SEER registries. Using SEER registry data, we linked all patients to a managing oncology physician. We collected data from the managing physician regarding receipt of TKIs and ICIs. We used bivariate analyses and multivariable logistic regression models to assess associations between non-receipt of TKIs and ICIs and patient-level factors. Results: We present results for a preliminary sample (N=894). About half (55%) of the patients had NSCLC, 31% had GU cancer, and 14% had melanoma. The mean age was 62 (SD 12); 59% were male; 65% were White, 16% were Black, 11% were Hispanic, and 7% were Asian; 52% had Medicare, 29% had private insurance, 9% had Medicaid, and 4% had no insurance; 89% resided in urban areas, 11% resided in rural areas. 22% lived in a census tract area with ≥20% of the population living below the poverty level. The Table shows that in bivariate analyses, non-receipt of TKIs was associated with NSCLC, older age, male sex, non-white race, and non-private or no insurance (all p<0.05). After adjustment, non-receipt of TKIs was associated with NSCLC, older age, male sex, and race. Asian and Hispanic patients had lower rates of non-receipt, and Black patients had higher rates. In bivariate analyses, non-receipt of ICIs was associated with NSCLC and GU cancer (p=0.004); this association remained significant after adjustment. Conclusions: Non-receipt of TKIs was associated with important non-clinical factors including race and sex. Non-receipt of ICIs was associated only with cancer type. These findings suggest that policy-relevant factors such as out-of-pocket costs for oral cancer therapies and differential access to molecular sequencing may contribute to unwarranted variation in receipt of TKIs. [Table: see text]

Deep learning–based chest CT model to predict treatment response to immune checkpoint inhibitors in non-small cell lung cancer independently and additively to histopathological biomarkers.

8536 Background: Immune checkpoint inhibitors (ICI) are an integral part of the treatment for advanced or metastatic non-small cell lung cancer (NSCLC). Chest CT and pathology data is gathered in routine clinical practice, and each modality provides complementary information. Tumor microenvironment is spatially heterogeneous and temporally dynamic. CT images provide macro-level characteristics of multiple tumors, and tissue-based histopathologic biomarkers analyze a single representative tumor microenvironment in-depth. We developed a deep learning-based chest CT prediction model to predict response to ICIs and validated its performance independently and in combination with histopathologic biomarkers. Methods: NSCLC patients treated with ICI monotherapy were retrospectively enrolled from Samsung Medical Center. A deep learning CT prediction (DL-CT) model was trained on the data of 1876 patients where time to next treatment (TTNT) was used as a proxy. A pre-trained CT nodule detection model was used to extract intermediate features from chest CT taken at a time closest to the initiation of ICI. Histopathologic biomarkers include tumor infiltrating lymphocytes (TIL) and immune phenotype analyzed by an AI analyzer (Lunit SCOPE IO) in H&E whole slide images and PD-L1 tumor proportion score (TPS) interpreted by human pathologists. The performance of DL-CT model was validated in an independent test set of 489 NSCLC patients. Results: In the test set, median follow up was 11.3 months. Patients predicted as a responder by DL-CT model (CT-responder) had prolonged TTNT (median TTNT: 7.0m vs. 2.5m, hazard ratio [HR] 0.588, p <0.001) and overall survival (OS) (median OS: 16.5m vs 7.6m, HR 0.581, p <0.001). The responder group predicted by DL-CT model was associated with better ECOG performance score (p = 0.012) and current smoking (p <0.001), but not with TIL-based immune phenotype or PD-L1 expression (p = 0.201 and p = 0.312, respectively). CT-responder showed favorable outcome across all PD-L1 subgroups (HR for TTNT 0.509, p = 0.005 for TPS 0%, HR 0.616, P = 0.015 for TPS 1-49% and HR 0.585, p <0.001 for TPS ≥50%) and immune phenotypes (HR for TTNT 0.543, p <0.001 for inflamed and HR 0.611, p <0.001 for non-inflamed). Combining DL-CT and histopathologic biomarkers, patients having all three biomarkers positive (CT-responder, inflamed and PDL1 TPS ≥50%) had substantially longer TTNT and OS compared to the other patients (mTTNT 9.4m vs. 3.5m, p<0.001 and mOS 32.0m vs. 10.0m vs. p <0.001). Conclusions: The AI model based on chest CT data was a strong independent biomarker to predict treatment response to ICI, which possibly reflects patients’ clinical characteristics. Combining AI CT model and histopathologic biomarkers showed additive impact on the prediction of the treatment response to ICI.

Experience with de-intensification of intensified treatment in metastatic castration-sensitive prostate cancer in Venezuela: A pilot study.

Experience with de-intensification of intensified treatment in metastatic castration-sensitive prostate cancer in Venezuela: A pilot study.

Noncanonical RET fusions in Chinese patients with non-small cell lung cancer from DNA-based next-generation sequencing.

e20000 Background: The FDA has approved selpercatinib and pralsetinib for the treatment of metastatic RET fusion-positive non-small cell lung cancer in adult patients. Although the overall response rate is high and the response is durable, the outcomes may vary due to different fusion types of the same driver gene. Methods: We retrospectively collected and analyzed 14062 samples (tumour tissue or plasma) from Chinese lung cancer patients who underwent tissue-based or ctDNA-based next-generation sequencing (NGS) assays at HaploX Genomic Sequencing Center from May 18, 2020, to January 11, 2024. All samples with a RET gene fusion were included and classified based on the fusion partner gene and breakpoint position. Results: A total of 157 (1.1%) samples with DNA-based NGS harbored a RET gene fusion. Among the samples with a RET gene fusion, the most common RET fusion partners at the DNA level were KIF5B (73.2%) and CCDC6 (21.0%). We categorized RET fusions into canonical fusions and noncanonical fusions based on fusion partner and breakpoint position, and the proportions of canonical fusions and noncanonical fusions were 88.5% (139/157) and 11.5% (18/157) respectively. Among the samples with a noncanonical RET fusion, 5 samples harbored a RET fusion with an uncommon fusion partner, it remains unclear whether these fusions lead to RET activation. Conclusions: In this retrospective study, we identify different types of RET fusions in Chinese lung cancer patients. The majority are canonical fusions, which can benefit from tyrosine kinase inhibitors in clinical, the rest are noncanonical fusions, and their role in precision therapy needs further verification by RNA-based NGS or other assays. All in all, our research helps guide precision therapy in clinical settings. [Table: see text]

Association of baseline characteristics with adverse events (AEs) in the PROpel trial of olaparib (ola) plus abiraterone (abi) as first-line (1L) treatment for metastatic castration-resistant prostate cancer (mCRPC).

e17030 Background: The PROpel trial (NCT03732820) met its primary endpoint and showed a statistically significant radiographic progression-free survival benefit (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54–0.81; P<0.0001) with ola + abi vs placebo + abi in 1L mCRPC; whilst not statistically significant, overall survival (OS) was numerically prolonged (median 42.1 vs 34.7 months; HR 0.81, 95% CI 0.67–1.00; P=0.0544). To further inform clinical decision making, we provide exploratory post hoc analysis investigating the relationship between selected patient baseline characteristics and AEs for ola + abi. Methods: Anemia and venous thromboembolism events (VTEs) were identified as the only grade (Gr) ≥3 AEs or AEs of special interest reported in >20 (>5.0%) patients (pts) in the ola + abi arm (data cutoff 12 Oct 2022). Baseline characteristics were correlated with AEs using Cox regression by backwards elimination and analysis with AEs as dependent variables. Baseline characteristics assessed included: age (<70 or ≥70 y), time since diagnosis (<median or ≥median) , ECOG status (0 or 1), metastatic sites (visceral [yes or no], bone only [yes or no]), number of bone metastases (0, 1–4, 5‒9, 10‒20 or >20), Gleason score (<9 or 9–10), homologous recombination repair mutation status (HRRm, non-HRRm or unknown), race (white or non-white), prior docetaxel at metastatic hormone-sensitive prostate cancer (yes or no), pain (symptomatic or asymptomatic/mildly symptomatic), type of progression (prostate-specific antigen [PSA], radiographic or both), prior radiotherapy (yes or no) and albumin, creatinine, lactate dehydrogenase, alkaline phosphatase (ALP), hemoglobin (10<12 or ≥12) and log PSA levels. Results: 398 pts received ola + abi. 64 (16.1%) had Gr ≥3 anemia and 34 (8.5%) a VTE. Baseline characteristics correlated significantly with increased risk of these AEs as shown (Table); characteristics not shown were not associated with AEs. Conclusions: These results provide insight into which baseline characteristics correlate with the risk of Gr ≥3 anemia. Pts with abnormal ALP, pre-existing anemia, ECOG PS 1 or age ≥70 years could be at higher risk and the development of Gr ≥3 anemia during treatment with ola + abi should be monitored. Clinical trial information: NCT03732820 . [Table: see text]

Updated estimates of eligibility and response: Immune checkpoint inhibitors.

e14613 Background: Immune checkpoint inhibitors (ICIs) have notably changed the landscape of systemic treatment of advanced and metastatic cancers in the last decade. We previously estimated the eligibility for and responses to ICIs, but since then, there have been multiple approvals for additional indications. As such, we have updated these estimates to include all approvals, as of December 2023. Methods: For eligibility, we used death data from the American Cancer Society’s Cancer Facts and Figures. Deaths was used as a stand-in for eligibility because these therapies are often given in later lines. Data from the peer-reviewed literature was used to further refine specific tumor type estimates (e.g., the percentage of lung cancers that are non-small cell and small cell lung cancer). For each tumor type, we multiplied the response rates reported in the FDA’s package insert by the number of deaths for each respective tumor type. When multiple drugs were approved for the same indication, we used the highest response rate. Results: Eleven ICI drugs were approved for 88 different indication approvals in the advanced/metastatic setting between 2015 and 2023. These approvals were for 20 general tumor types. The estimated eligibility for ICIs increased from 1.54% in 2011 to 55.47% in 2023. The tumor types with the highest eligibility in 2023 were non-small cell lung cancer with PDL1 status of 50% (13.28%) or less and PDL1 status >50% (4.42%), solid tumors TMB-h (6.81%), and hepatocellular (4.82%). The estimated response to ICIs increased from 0.14% in 2011 to 19.60% in 2023. The tumor types with the highest contribution to response estimates in 2023 were non-small cell lung cancer with PDL1 status of 50% (4.78%) or less and PDL1 status >50% (1.99%), solid tumors TMB-h (2.72%), and renal cell carcinoma (1.95%). Conclusions: We find that the estimated eligibility for and response to ICIs has increased since their introduction in 2011. Our estimates are an upper bound since many people are not eligible due to contraindications or healthcare coverage. Both the response and eligibility were driven by certain tumor types, including non-small cell lung cancer (either PDL1 high or PDL1 low). Patients with these types of tumors made up about one-third of the estimated response and eligibility. Solid tumors TMB-h, hepatocellular and renal cell carcinoma were other tumors with high eligibility and response, but other tumor types had low eligibility and response. While many patients have benefited from ICIs, half of patients with advanced or metastatic cancers are either not eligible or likely do not respond. [Table: see text]

Anlotinib combined with penpulimab as first-line treatment for persistent, recurrent, or metastatic cervical cancer: Preliminary results from ALTER-GO-020, a single-arm, open-label, multi-cohort, multi-center phase II clinical study.

e17506 Background: The BEATcc trial demonstrated the combination of atezolizumab plus bevacizumab and platinum regimen as first-line treatment for recurrent, or metastatic cervical cancer significantly improves progression-free survival (PFS) and overall survival (OS) regardless of PD-L1 status. ALTER-GO-020 is an ongoing open-label, single-arm, multi-cohort phase II study evaluating the combination of anlotinib (a multitarget anti-angiogenic TKI) and penpulimab (anti-PD-1 antibody) as a chemotherapy-free regimen for patients (pts) with recurrent or metastatic gynecological cancer. Here, we report the preliminary results of the cohort of patients with recurrent or metastatic cervical cancer from ALTER-GO-020. Methods: Eligible pts were histologically confirmed persistent, recurrent, or metastatic cervical cancer (including adenocarcinoma, adenosquamous carcinoma, or squamous-cell carcinoma), not amenable to curative treatment, and had no prior systemic treatment for metastatic, persistent, or recurrent disease. Pts were treated with anlotinib (12mg, po qd, d1-14, q3w) plus penpulimab (200mg, IV, d1, q3w) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included PFS, duration of response (DOR), disease control rate (DCR), OS and safety. Results: From May 2022 to Nov 2023, 17 pts were enrolled. The median age was 52 years (range, 31-70), 65% of pts were squamous-cell carcinoma, 88% received previous chemoradiotherapy with or without surgery, and 71% had previously received neoadjuvant/adjuvant platinum-containing chemotherapy. As of date cutoff (Dec, 2023), the median follow-up time was 6.8 months (range, 1.4-18.3 months). In the efficacy analysis (n=17), the preliminary ORR was 58.8% (95% CI: 32.9%-81.6%), DCR was 88.2% (95% CI: 63.6%-98.5%). The mPFS was 11.0 months (95% CI: 5.4-16.7 months). The mOS was not reached. Treatment-related adverse events (TRAEs) of any grade occurred in all 17 pts, in which 8 (47.1%) were grade ≥3. The most common grade ≥3 TRAEs were hypertension (29.4%), hand foot syndrome (11.8%), fatigue (11.8%), and diarrhea (5.9%). TRAEs led to dose reduction and interruption were 29.4%, and 35.3% of pts, respectively. No TRAEs leading to death. Conclusions: The preliminary results demonstrated that anlotinib plus penpulimab as a first-line therapy for persistent, recurrent, or metastatic cervical cancer showed promising antitumor efficacy and manageable safety profile. Clinical trial information: NCT05028504 .

Health outcomes of pembrolizumab plus chemotherapy in non-small cell lung cancer.

e20527 Background: Pembrolizumab (PEM) is a standard of treatment for advanced or metastatic non-small cell lung cancer (m-nSCLC) in tumors without biomarker actionable. The clinical practice protocol for m-nSCLC in our hospital includes PEM monotherapy if PD-L1 ≥50% and PEM+chemotherapy (PEM+CT) if PD-L1 1-49% or negative. The aim of this study is to determine the effectiveness results of PEM+CT in m-nSCLC in real clinical practice. Methods: It was designed a single center, observational and retrospective study. We included all patients (pts) treated with PEM+CT as first line of therapy with m-nSCLC of September-2019 to August-2023 at a hospital from south Spain, cut-off date 11/30/2023. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The results were analyzed for population and by subgroups (histology, ECOG, previous localized disease (LD) and other), using Kaplan-Meier method. Results: 103 pts were enrolled (89% men), mean age was 66.2 years, 48.5% of pts had ECOG 0, 40.8% ECOG 1 and the rest ECOG 2-3. The tumors were 64.1 % non-squamous histology. 28.2% pts were treated for previous localized disease and 39.8% pts received radiation therapy at some point during treatment. At start of therapy the mean WBC count with PEM+CT was 10.0 x10(9)/L (sd=6.2). With a median follow-up of 10.8 months (m) the median for treatment duration was 5.7 m [95%CI 4.3-7.2].PFS was 7.2 m [IC95% 5.9-8.6] for all pts, 6.6 m [IC95% 4.6-8.7] for non-squamous and 8.2 m [IC95% 4.6-11.7] for squamous histology, p=0.158. OS was 14.2 m [IC95% 10.2-18.2] for all pts, 13.1 m [IC95% 7.6-18.6] and 14.2 [IC95% 9.3-19.2] by non-squamous and squamous histology, respectively, p=0.396.We found statistically significant difference in OS between: pts with ECOG 0-1 (median 15.1 m [IC95% 11.6-18.7]) vs pts with EOCG 2-3 (median 6.6 m [IC95% 1.6-11.6]), p=0.046 and pts previously treated pts of LD (median 21.7 m [IC95% 2.5-40.8]) vs pts with advanced or metastatic disease at onset (median 10.5 m [IC95% 5.2-15.9]), p=0.025. Another subgroup analysis is shown in table. Conclusions: The effectiveness of PEM+CT was similar in OS and PFS values to that of the pivotal trials. In contrast to these, our results were slightly better in squamous histology. The OS was better in pts with ECOG 0-1 and previously treated of localized disease, highlighting the importance of early diagnosis. [Table: see text]

Real-world data of a regimen containing zimberelimab in the treatment of recurrent and metastatic cervical cancer.

e17521 Background: Cervical cancer is the malignant tumor in women. Zimberelimab is approved by NMPA for PD-L1 positive recurrent and metastatic cervical cancer. However, no real-world data of zimberelimab in recurrent and metastatic cervical cancer have been reported before. Methods: From August 2021 to March 2023, we retrospectively collected patient data at the First Affiliated Hospital of Nanchang University and Fujian Cancer Hospital. Patients with advanced or recurrent cervical cancer who had been pathologically diagnosed were eligible, regardless of whether they had squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma and PD-L1 status. All patients were treated with regimen containing zimberelimab. Date of brith, previous medical history, tumor stage at first diagnosis, metastatic sites, pathological type, HPV infection and PD-L1 expression status, and treatment regimen containing zimberelimab will be recorded. The primary endpoint was objective response rate and disease control rate assessed by RECIST1.1. The study has been approved by the First Affiliated Hospital of Nanchang University Ethics (No 317). (ChiCTR2300078205). Results: A total of 34 patients were eligible for evaluations of efficacy. 21 from the First Affiliated Hospital of Nanchang University and 13 from the Fujian Cancer Hospital. The median age was 53.23 years (range, 37–66). The ECOG PS was 1 for 23 cases (67.65%), 2 for 10 cases (29.41%).3 for 1 case (2.94%). Squamous cell carcinoma (28,82.35%) was the most common pathological subtype, and the most metastatic site were lymph node (26,76.47%), lung (10,29.41%), bone (6,17.65%), liver (1,2.94%), vulva (1,2.94%), peritoneal (1,2.94%) and bladder (1,2.94%). 32(94.12%) and 30(88.24%) patients have not test for PD-L1 statue or HPV infection. The best overall response of each patient was recorded to evaluate the efficacy. The objective response rate (ORR) in 34 patients were 52.94%, and the disease control rate (DCR) were 97.06%. And 25 patients had previously had ≥1 chemotherapy, and they was treated with a zimberelimab-based combination regimen. The ORR and DCR for these individuals were 52% and 96%, respectively. Conclusions: This is the first report of real-world data on zimberelimab, and zimberelimab combination therapy demonstrated quite good efficacy in patients with recurrence and metastatic cervical cancer who had previously received chemotherapy. Clinical trial information: ChiCTR2300078205. [Table: see text]

A single-arm, phase II trial assessing the combination of AK105 and anlotinib in first-line treatment for persistent, recurrent, or metastatic cervical cancer.

A single-arm, phase II trial assessing the combination of AK105 and anlotinib in first-line treatment for persistent, recurrent, or metastatic cervical cancer.