Prolonged Progression-free Survival Research Articles

Efficacy and safety of apatinib plus immune checkpoint inhibitors and transarterial chemoembolization for the treatment of advanced hepatocellular carcinoma.

The evidence of apatinib plus immune checkpoint inhibitors (ICIs) and transarterial chemoembolization (TACE) for treating advanced hepatocellular carcinoma (HCC) is limited. This study aimed to compare the treatment efficacy and safety of apatinib plus ICIs and TACE with apatinib plus TACE in these patients. This study retrospectively enrolled 90 patients with advanced HCC treated with apatinib plus TACE (A-TACE group, n = 52) or apatinib plus ICIs and TACE (IA-TACE group, n = 38). The objective response rate was numerically higher in IA-TACE group compared with A-TACE group without statistical significance (57.9% vs. 36.5%, P = 0.055). Disease control rate was not different between groups (86.8% vs. 76.9%, P = 0.248). Progression-free survival (PFS) was improved in IA-TACE group compared with A-TACE group (P = 0.018). The median PFS (95% confidence interval) was 12.5 (8.7-16.3) months in IA-TACE group and 8.5 (5.6-11.4) months in A-TACE group. Overall survival (OS) was also prolonged in IA-TACE group compared with A-TACE group (P = 0.007). The median OS (95% confidence interval) was 21.1 (15.8-26.4) months in IA-TACE group and 14.3 (11.5-17.1) months in A-TACE group. By multivariate Cox regression model, IA-TACE was independently associated with prolonged PFS (hazard ratio = 0.539, P = 0.038) and OS (hazard ratio = 0.447, P = 0.025). Most adverse events were not different between groups. Only the incidence of reactive cutaneous capillary endothelial proliferation was higher in IA-TACE group compared with A-TACE group (10.5% vs. 0.0%, P = 0.029). Apatinib plus ICIs and TACE may be an effective and safe treatment for patients with advanced HCC, but further large-scale studies are needed for verification.

Efficacy and safety of multikinase inhibitors for patients with refractory thyroid cancer: Systematic review and network meta-analysis.

Multikinase inhibitors (MKIs) improve the treatment of refractory thyroid cancer, included radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and advanced medullary thyroid carcinoma (aMTC). This study aims to compare the efficacy of MKIs in improving survival outcomes and safety. Comprehensive database searches of MEDLINE via PubMed, EMBASE and Cochrane performed from inception to December 2023. Three independent authors selected these studies. Randomised-controlled trials that compared the use of a MKI to other MKIs or placebo were included. This review followed PRISMA guidelines. Risk of bias was analyzed using the Cochrane RoB 2 tool. Bayesian network meta-analysis was performed. Treatments were grouped into common nodes based on the type of MKI. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate, disease control rate, clinical benefit rate, and adverse events. Cabozantinib 60 mg/d (CAB60) was associated with the highest prolonged PFS in RAIR-DTC patients, followed by lentivatinib 18 or 24 mg/d (LEN18 or LEN24), and apatinib. PFS was also improved in in aMTC patients received CAB 140 mg/d (CAB140), CAB60, or anlotinib. A significantly greater improvement on the performance of OS was seen in CAB60, LEN24, anlotinib, and sorafenib in RAIR-DTC patients, but which in aMTC patients were lack of statistical differences. Compared with the low-dose of MKIs, high-dose of MKIs such as CAB, LEN, and vandetanib increased the incidence of adverse events. CAB60, LEN, and apatinib are promising topical MKIs with statistically significant primary outcomes in RAIR-DTC patients, while CAB and anlotinib are effective in prolonging PFS in aMTC patients.

Identification of peripheral blood test parameters predicting the response to palbociclib and endocrine therapy for metastatic breast cancer: a retrospective study in a single institution.

Cyclin-dependent kinase 4/6 inhibitors have been used in endocrine therapy for patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. Although randomized trials have shown that combined therapies prolong progression-free survival (PFS) in comparison to endocrine monotherapy, the predictors of efficacy are unknown. This study aimed to identify the blood test parameters to predict the effects of palbociclib and endocrine therapy. Seventy-nine patients treated with palbociclib and endocrine therapy between December 2017 and June 2022 were reviewed. We assessed PFS in patients according to factors evaluated based on patient characteristics and peripheral blood tests. Patients in the C-reactive protein (CRP)-high, lactate dehydrogenase (LDH)-high, and albumin (Alb)-low groups had significantly shorter PFS than those in the normal group. A multivariate analysis revealed that high LDH and low Alb levels were independent factors that affected PFS. The Alb-low group had an inferior disease control rate. Patients in the CRP-high, LDH-high, and Alb-low groups who received these therapies as first- or second-line treatments showed poor PFS. Several predictors of the efficacy of palbociclib and endocrine therapy were identified in the peripheral blood test parameters of patients with ER-positive and HER2-negative subtypes of metastatic breast cancer.

Prognostic Value of Alpha-Fetoprotein in Unresectable Hepatocellular Carcinoma Treated with Hepatic Artery Infusion Chemotherapy Combined with Lenvatinib and Camrelizumab.

This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab. A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a >20% decrease in AFP within 4 weeks, and AFP response as a >75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated. The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p<0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p<0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333-6.585, p=0.008, and HR 6.182, 95% CI 1.780-21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107-4.318, p=0.024, and HR 3.078, 95% CI 1.407-6.730, p=0.005), serving as significant prognostic values. Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.

Systematic review on the efficacy and safety of ixabepilone-based chemotherapy regimen in triple-negative breast cancer

Context: Triple-negative breast cancer (TNBC) has poor prognosis, high mortality, and recurrence rates. Ixabepilone or ixempra could be a promising agent for TNBC, especially in the taxane- and/or anthracycline-resistant population. Aims: To evaluate the efficacy and safety of ixabepilone-based chemotherapy compared to ixabepilone-free chemotherapy in TNBC patients. Methods: This review followed the preferred reporting items for systematic reviews and meta-analysis guidelines. The eligibility criteria included randomized control trials (RCTs) in 2013-2023 comparing ixabepilone-based with ixabepilone-free chemotherapy regimen in TNBC. Results: This study identified four eligible RCTs. One study showed that patients treated with ixabepilone had a significant improvement in disease-free survival, had a better response, and a lower risk of disease recurrence compared to those treated with taxane-based regimen. However, two studies showed no differences in terms of overall survival (OS), disease-free survival, and pathological complete responses rates in both treatment arms. Ixabepilone addition to capecitabine significantly prolonged progression-free survival and objective response rate in TNBC patients, but did not significantly improve OS (n = 1). Conclusions: The effectiveness and safety of ixabepilone-based chemotherapy versus ixabepilone-free treatment for triple-negative breast cancer (TNBC) patients vary among studies. More research is needed to better understand the effectiveness and safety of ixabepilone-based chemotherapy versus ixabepilone-free treatment in TNBC patients.

LINC01432 binds to CELF2 in newly diagnosed multiple myeloma promoting short progression-free survival to standard therapy.

Multiple Myeloma (MM) is a highly prevalent and incurable form of cancer that arises from malignant plasma cells, with over 35,000 new cases diagnosed annually in the United States. While there are a growing number of approved therapies, MM remains incurable and nearly all patients will relapse and exhaust all available treatment options. Mechanisms for disease progression are unclear and in particular, little is known regarding the role of long non-coding RNAs (lncRNA) in mediating disease progression and response to treatment. In this study, we used transcriptome sequencing to compare newly diagnosed MM patients who had short progression- free survival (PFS) to standard first-line treatment (PFS < 24 months) to patients who had prolonged PFS (PFS > 24 months). We identified 157 differentially upregulated lncRNAs with short PFS and focused our efforts on characterizing the most upregulated lncRNA, LINC01432 . We investigated LINC01432 overexpression and CRISPR/Cas9 knockdown in MM cell lines to show that LINC01432 overexpression significantly increases cell viability and reduces apoptosis, while knockdown significantly reduces viability and increases apoptosis, supporting the clinical relevance of this lncRNA. Next, we used individual-nucleotide resolution cross-linking immunoprecipitation with RT-qPCR to show that LINC01432 directly interacts with the RNA binding protein, CELF2. Lastly, we showed that LINC01432 -targeted locked nucleic acid antisense oligonucleotides reduce viability and increases apoptosis. In summary, this fundamental study identified lncRNAs associated with short PFS to standard NDMM treatment and further characterized LINC01432, which inhibits apoptosis. Key points: lncRNA expression was found to be dysregulated in patients with short PFS to standard multiple myeloma therapy. LINC01432 -bound CELF2 inhibits apoptosis.

Efficacy and safety of sintilimab in combination with chemotherapy for recurrent extensive-stage small cell lung cancer: a real-world retrospective study.

Immune checkpoint inhibitors (ICIs) no longer are approved for second-line or later treatment of extensive-stage small cell lung cancer (ES-SCLC), and have not been studied in combination with chemotherapy. Exploring the efficacy and safety of second-line or later immunotherapy for ES-SCLC is an urgent clinical question that needs to be addressed, and combination therapies are an important research direction. This study intended to investigate the efficacy and safety of the sintilimab in combination with chemotherapy as a second-line and beyond treatment option for ES-SCLC. Medical records of patients who received treatment with sintilimab in combination with chemotherapy or chemotherapy alone as a second-line or beyond therapy were retrospectively analyzed. The study evaluated efficacy and safety. Indicators of efficacy included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Safety indicators included adverse events (AEs). This cohort comprised of 46 patients: 24 in the sintilimab combination chemotherapy group and 22 in the chemotherapy group. Chemotherapy received by both groups was either albumin-bound paclitaxel or irinotecan. Compared with the chemotherapy group, the sintilimab combination chemotherapy group had higher ORR and DCR (ORR: 37.5% vs. 9.1%, P=0.04; DCR: 75.0% vs. 40.9%, P=0.04), and significantly prolonged PFS and OS [median PFS (mPFS): 5.07 vs. 2.45 months, P=0.006; median OS (mOS): 14.43 vs. 10.34 months, P=0.009]. Also, there was no significant increase in the incidence of AEs in the sintilimab combination chemotherapy group, which was well tolerated by patients. Sintilimab in combination with chemotherapy is superior to single-agent chemotherapeutic treatment as second-line or later therapy in ES-SCLC patients who have not received prior immunotherapy. These results need to be confirmed in future clinical trials.

Primary Malignant Melanoma of the Cervix with Rapidly Progressing Metastases

Introduction: Mucosal melanomas only account for 0.03% of newly diagnosed cancer cases. Female genital tract melanomas account for only 3% of all melanomas, with melanoma of the cervix accounting for less than 3% of all female genital tract melanomas. It is difficult to understand how mucosal melanomas arise as the pathogenesis is still unknown. The incidence of cutaneous melanoma has greatly increased over the years whereas the incidence of mucosal melanomas has stayed relatively steady. Given the rarity of melanoma of the cervix, a standard of care treatment has not been established. Based on the limited cases that have previously been treated, the first option is surgery for early stage melanomas with adjuvant radiation therapy indicated in some cases. The use of systemic chemotherapy is still controversial as it has not been shown to prevent metastases. Case Report: A 66-year-old postmenopausal female presented with heavy vaginal bleeding. A transvaginal ultrasound showed a complex cystic structure in the cervix and she was referred to gynecologic oncology. She was up to date on her pap smears, and they have always been normal. Patient was found to have a fungating 4 x 5 cm mass in the upper vagina and pathology demonstrated poorly differentiated malignant neoplasm. The patient was diagnosed with FIGO Stage IIA2 cervical cancer. Patient’s initial PET/CT demonstrated hypermetabolic area in the cervix consistent with known cervical carcinoma with no other uptake in the uterus. Weekly chemosensitization with cisplatin and external beam radiation was initiated. On clinical examination after treatment by the gynecologic oncologist, visible disease was seen confined to the cervix. An MRI of the pelvis showed response with the suspected tumor limited to the cervical stroma in the anterior and lateral portion of the cervix with no definitive parametrial tumor and no evidence of nodal metastasis. Second opinion from pathology review was received and results showed poorly differentiated malignant neoplasm immunohistochemically consistent with “melanoma”. After 25 fractions of daily radiotherapy with weekly cisplatin, patient underwent exploratory laparotomy for radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node sampling. Final pathology of the uterus and cervix showed invasive poorly differentiated melanoma with deepest invasion of melanoma measuring 8mm and negative surgical margins. All lymph nodes removed during surgery were negative for malignancy. Adjuvant Pembrolizumab was started at this time. Two months postoperatively, the patient underwent CT surveillance again due to new onset chest wall and axillary nodules varying in size from 2-4 cm. Right chest wall axilla biopsy pathology was consistent with melanoma. At this time Pembrolizumab was discontinued and the patient was transitioned to Nivolumab and Ipilimumab 19 days after discontinuing Pembrolizumab. Four months postoperatively, additional CT scans were performed showing widespread metastatic disease in the lungs, chest wall, liver, peritoneum, retroperitoneum and left eye. Patient underwent left frontal craniotomy with tumor resection, and pathology was consistent with metastatic melanoma. Subsequent to craniotomy, the patient underwent three treatments with stereotactic radiosurgery. Despite treatment, six months postoperatively, the patient’s symptoms continued to progress with slurred speech, generalized weakness and abdominal pain. Ultimately, the patient passed away nine months after the diagnosis and four months after a combination of external beam radiotherapy, surgery, and vaginal brachytherapy. Discussion: Melanoma of the cervix is a rare type of cervical cancer with poor prognosis. Globally, 5-year survival is 18.8% for stage I, 11.1% for stage II, and 0% for stages III–IV. It has been shown that median overall survival time decreases with increasing FIGO stage. Risk factors have not been identified for gynecologic melanomas or most other mucosal melanomas. Pembrolizumab is most effective for cutaneous melanomas, however, has been shown to prolong progression free survival in mucosal melanomas. The median overall survival is significantly shorter for patients with mucosal melanoma (11.3 months) as compared to patients with a cutaneous primary (23.5 months). Primary malignant melanoma of the cervix (PMMC) remains a rare tumor and the prognosis is generally poor. Radical hysterectomy, chemoradiation, and immunotherapy have all been utilized in the treatment of PMMC. Further investigation of primary melanoma of the cervix is necessary to formulate a standard of care treatment.

Primary Malignant Melanoma of the Cervix with Rapidly Progressing Metastases

Introduction: Mucosal melanomas only account for 0.03% of newly diagnosed cancer cases. Female genital tract melanomas account for only 3% of all melanomas, with melanoma of the cervix accounting for less than 3% of all female genital tract melanomas. It is difficult to understand how mucosal melanomas arise as the pathogenesis is still unknown. The incidence of cutaneous melanoma has greatly increased over the years whereas the incidence of mucosal melanomas has stayed relatively steady. Given the rarity of melanoma of the cervix, a standard of care treatment has not been established. Based on the limited cases that have previously been treated, the first option is surgery for early stage melanomas with adjuvant radiation therapy indicated in some cases. The use of systemic chemotherapy is still controversial as it has not been shown to prevent metastases. Case Report: A 66-year-old postmenopausal female presented with heavy vaginal bleeding. A transvaginal ultrasound showed a complex cystic structure in the cervix and she was referred to gynecologic oncology. She was up to date on her pap smears, and they have always been normal. Patient was found to have a fungating 4 x 5 cm mass in the upper vagina and pathology demonstrated poorly differentiated malignant neoplasm. The patient was diagnosed with FIGO Stage IIA2 cervical cancer. Patient’s initial PET/CT demonstrated hypermetabolic area in the cervix consistent with known cervical carcinoma with no other uptake in the uterus. Weekly chemosensitization with cisplatin and external beam radiation was initiated. On clinical examination after treatment by the gynecologic oncologist, visible disease was seen confined to the cervix. An MRI of the pelvis showed response with the suspected tumor limited to the cervical stroma in the anterior and lateral portion of the cervix with no definitive parametrial tumor and no evidence of nodal metastasis. Second opinion from pathology review was received and results showed poorly differentiated malignant neoplasm immunohistochemically consistent with “melanoma”. After 25 fractions of daily radiotherapy with weekly cisplatin, patient underwent exploratory laparotomy for radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node sampling. Final pathology of the uterus and cervix showed invasive poorly differentiated melanoma with deepest invasion of melanoma measuring 8mm and negative surgical margins. All lymph nodes removed during surgery were negative for malignancy. Adjuvant Pembrolizumab was started at this time. Two months postoperatively, the patient underwent CT surveillance again due to new onset chest wall and axillary nodules varying in size from 2-4 cm. Right chest wall axilla biopsy pathology was consistent with melanoma. At this time Pembrolizumab was discontinued and the patient was transitioned to Nivolumab and Ipilimumab 19 days after discontinuing Pembrolizumab. Four months postoperatively, additional CT scans were performed showing widespread metastatic disease in the lungs, chest wall, liver, peritoneum, retroperitoneum and left eye. Patient underwent left frontal craniotomy with tumor resection, and pathology was consistent with metastatic melanoma. Subsequent to craniotomy, the patient underwent three treatments with stereotactic radiosurgery. Despite treatment, six months postoperatively, the patient’s symptoms continued to progress with slurred speech, generalized weakness and abdominal pain. Ultimately, the patient passed away nine months after the diagnosis and four months after a combination of external beam radiotherapy, surgery, and vaginal brachytherapy. Discussion: Melanoma of the cervix is a rare type of cervical cancer with poor prognosis. Globally, 5-year survival is 18.8% for stage I, 11.1% for stage II, and 0% for stages III–IV. It has been shown that median overall survival time decreases with increasing FIGO stage. Risk factors have not been identified for gynecologic melanomas or most other mucosal melanomas. Pembrolizumab is most effective for cutaneous melanomas, however, has been shown to prolong progression free survival in mucosal melanomas. The median overall survival is significantly shorter for patients with mucosal melanoma (11.3 months) as compared to patients with a cutaneous primary (23.5 months). Primary malignant melanoma of the cervix (PMMC) remains a rare tumor and the prognosis is generally poor. Radical hysterectomy, chemoradiation, and immunotherapy have all been utilized in the treatment of PMMC. Further investigation of primary melanoma of the cervix is necessary to formulate a standard of care treatment.

Correlation between immune-related adverse events and efficacy of PD-(L)1 inhibitors in small cell lung cancer: a multi-center retrospective study.

Patients receiving PD-(L)1 inhibitors frequently encounter unusual side effects known as immune-related adverse events (irAEs). However, the correlation of irAEs development with clinical response in small cell lung cancer (SCLC) is unknown. This retrospective study enrolled 244 stage IV SCLC patients who receiving PD-(L)1 inhibitors from 3 cancer centers. The correlation of irAEs with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. 140 in 244 (57%) patients experienced irAEs, with 122 (87.1%) experiencing one and 18 (12.9%) experiencing two or more. Compared to patient without irAEs, those developing irAEs had higher ORR (73.6% vs. 52.9%, P < 0.001) and DCR (97.9% vs. 79.8%, P < 0.001), as well as prolonged median PFS (8.8 vs. 4.5 months, P < 0.001) and OS (23.2 vs. 21.6 months, P < 0.05). Among the different spectra of irAEs, thyroid dysfunction, rash, and pneumonitis were the most powerful indicator for improved PFS. When analyzed as a time-dependent covariate, the occurrence of irAEs was associated with significant improvement in PFS rather than in OS. Furthermore, patients experiencing multisystem irAEs displayed a longer PFS and OS compared with single-system irAEs and the irAE-free ones. IrAEs grade and steroid use did not impact the predictive value of irAEs on PFS. The presence of irAEs predicts superior clinical benefit in SCLC. Patients who develop multi-system irAEs may have an improved survival than those developed single-system irAEs and no-irAEs. This association persists even when systemic corticosteroids were used for irAEs management.

Body mass index and adiposity influence responses to immune checkpoint inhibition in endometrial cancer.

Obesity is the foremost risk factor in the development of endometrial cancer (EC). However, the impact of obesity on the response to immune checkpoint inhibitors (ICI) in EC remains poorly understood. This retrospective study investigates the association between body mass index (BMI), body fat distribution, and clinical and molecular characteristics of EC patients treated with ICI. We analyzed progression-free survival (PFS) and overall survival (OS) in EC patients treated with ICI, categorized by BMI, fat mass distribution, and molecular subtypes. Incidence of immune-related adverse events (irAE) after ICI was also assessed based on BMI status. 524 EC patients were included in the study. Overweight and obese patients exhibited a significantly prolonged PFS and OS compared to normal BMI patients after treatment with ICI. Multivariable Cox regression analysis confirmed the independent association of overweight and obesity with improved PFS and OS. Elevated visceral adipose tissue (VAT) was identified as a strong independent predictor for improved PFS to ICI. Associations between obesity and OS/PFS were particularly significant in the copy number-high/TP53abnormal (CN-H/TP53abn) EC molecular subtype. Finally, obese patients demonstrated a higher irAE rate compared to normal BMI individuals. Obesity is associated with improved outcomes to ICI in EC patients and a higher rate of irAEs. This association is more pronounced in the CN-H/TP53abn EC molecular subtype. NIH/NCI Cancer Center Support Grant P30CA008748 (MSK). K08CA266740 and MSK Gerstner Physician Scholars Program (J.C.O). RUCCTS Grant #UL1 TR001866 (N.G-B and C.S.J). Cycle for survival and Breast Cancer Research Foundation grants (B.W).

Effect of age on safety and efficacy of novel cancer drugs investigated in early-phase clinical trials

BackgroundElderly patients are underrepresented in clinical trials, particularly in early-phase studies. Our study assessed the safety and efficacy of novel anti-cancer treatments investigated in early-phase clinical trials, comparing outcomes between younger and elderly patients. MethodsThis retrospective study analyzed data from patients enrolled in phase I/II trials at our center between January 2014 and April 2021. We evaluated clinicopathologic characteristics, toxicity, and clinical efficacy, categorizing patients into younger (≤ 65 years) and elderly (> 65 years) groups. Results419 patients were included with a median age of 56 years. Among these, 107 (26 %) were older than 65 years. Predominant cancers included breast (48 %), lung (10 %), and melanoma (5 %). Patients were treated in 64 trials, predominantly receiving immunotherapy-based (47 %) or targeted therapy-based (45 %) treatment. Elderly presented with poorer ECOG performance status (P = 0.001) and had fewer prior therapy lines (P = 0.01) than younger patients. Grade ≥ 3 adverse events (AEs) were similar across age groups (31 % younger vs 33 % elderly; P = 0.7), including in combination therapy scenarios. However, elderly patients experienced more AEs with antibody-drug conjugates compared to younger counterparts (56 % vs 14 %, P = 0.036) and were more likely to discontinue treatment due to toxicity (15 % vs 7 %; P = 0.011). No significant age-related differences in response rates and survival outcomes were observed across treatment modalities, except for immunotherapy-based regimens for which elderly patients exhibited higher response rates, disease control rates, and prolonged progression-free survival. ConclusionsOur findings suggest that elderly exhibit comparable safety and efficacy outcomes to younger patients in early-phase clinical trials for new cancer drugs. This underscores the importance of including elderly patients in phase I/II trials to ensure the generalizability of study results and mitigate age-related disparities in cancer treatment access.

Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial.

LBA1001 Background: The combination of CDK4/6 inhibitors (CDK4/6i) + endocrine therapy (ET) is the standard first line treatment for HR+, HER2- advanced breast cancer (ABC). While disease progression occurs in nearly all patients (pts) with ABC, the optimal treatment for pts who experience progression on a CDK4/6i + ET remains uncertain. Real-world evidence suggests that use of abemaciclib after disease progression on a prior CDK4/6i prolongs progression-free survival (PFS) in ABC; however, Phase 2 trials with other CDK4/6i have generated mixed results. Here we present the primary outcome analysis for the Phase 3 postMONARCH trial (NCT05169567) of fulvestrant + abemaciclib or placebo in pts with HR+, HER2- ABC following disease progression on prior CDK4/6i + ET. Methods: postMONARCH was a global, double-blind, placebo-controlled study with pts randomized 1:1 to abemaciclib + fulvestrant or placebo + fulvestrant. Eligible pts had disease progression on a CDK4/6i + AI as initial therapy for ABC or relapse on/after a CDK4/6i + ET as adjuvant therapy for early breast cancer. No other prior treatment for ABC was permitted. Primary endpoint was investigator-assessed PFS; secondary endpoints included PFS by blinded independent central review (BICR), overall survival (OS), objective response rate (ORR), and safety. Assuming a hazard ratio (HR) of 0.7, the study had ~80% power to detect superiority for abemaciclib, with a cumulative 2-sided type I error of 0.05. Kaplan-Meier method was used to estimate PFS curves and treatment effect was estimated using a stratified Cox proportional hazard model. Results: A total of 368 pts were randomized to abemaciclib + fulvestrant (n = 182) or placebo + fulvestrant (n= 186). Most pts (99%) enrolled directly after CDK4/6i + ET as initial therapy for ABC. Prior CDK4/6i was 59% palbociclib, 33% ribociclib, and 8% abemaciclib. At interim analysis, the study reached the pre-specified criteria for significantly improved investigator-assessed PFS with abemaciclib + fulvestrant compared to placebo + fulvestrant (169 events, HR = 0.66; 95% CI 0.48 – 0.91; p = 0.01). At primary analysis (258 events), the HR was 0.73 (95% CI 0.57 – 0.95), with PFS rates at 6 months of 50% vs 37% for the abemaciclib and placebo arms, respectively. Consistent effect was seen across major clinical and genomic subgroups, including pts with baseline ESR1 or PIK3CA mutations. ORR was improved with abemaciclib compared to placebo (17% vs 7%, respectively, in pts with measurable disease). PFS according to BICR was also improved with HR = 0.55 (95% CI 0.39 - 0.77). OS remains immature (20.9% event rate). Safety was consistent with the known profile of abemaciclib. Conclusions: Abemaciclib + fulvestrant demonstrated statistically significant PFS improvement in pts with ABC progression on prior CDK4/6i-containing therapy. Clinical trial information: NCT05169567 .

Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non-Small Cell Lung Cancer: The Phase II TRUST-I Study.

Taletrectinib, a highly potent, CNS-active, ROS1 tyrosine kinase inhibitor (TKI), has demonstrated high and durable response rates, high intracranial objective response rate (ORR), prolonged progression-free survival (PFS), and activity against G2032R with a favorable safety profile. We report outcomes from the pivotal TRUST-I study (ClinicalTrials.gov identifier: NCT04395677) of taletrectinib for ROS1+ non-small cell lung cancer in China. TRUST-I evaluated TKI-naїve and crizotinib-pretreated patients. The primary end point was confirmed ORR (cORR) by independent review committee; key secondary end points included duration of response (DOR), PFS, and safety. As of November 2023, 173 patients were enrolled (median age, 55 years; 58% female; 73% never smoked; TKI naїve: n = 106; crizotinib pretreated: n = 67). In TKI-naїve patients, cORR and intracranial cORR were 91% and 88%, respectively, and 52% and 73% in crizotinib-pretreated patients. In TKI-naїve patients, median DOR and median PFS were not reached (NR) with 22.1-month and 23.5-month follow-up, respectively. In crizotinib-pretreated patients, the median DOR was 10.6 months (95% CI, 6.3 months to NR; 8.4-month follow-up), and the median PFS was 7.6 months (95% CI, 5.5 to 12.0 months; 9.7-month follow-up). Eight of 12 patients (67%) with G2032R mutations responded. The most frequent treatment-emergent adverse events (TEAEs) were increased AST (76%), diarrhea (70%), and increased ALT (68%), most of which were grade 1-2. Incidences of neurologic TEAEs were low (dizziness: 23%; dysgeusia: 10%) and mostly grade 1. Discontinuations (5%) and dose reductions (19%) due to TEAEs were low. Taletrectinib continues to show high and durable overall responses, prolonged PFS, robust activity against intracranial lesions and acquired resistance mutations including G2032R, and a favorable safety profile with a low incidence of neurologic TEAEs.

TACE combined with tislelizumab and lenvatinib in the treatment of advanced liver cancer: A real world study.

e16270 Background: The combination of transcatheter arterial chemoembolization (TACE) plus Lenvatinib prolonged progression-free survival (PFS) and overall survival (OS) than Lenvatinib or TACE monotherapy for patients with hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of Lenvatinib plus monoclonal antibody against programmed cell death 1 (anti-PD1) and TACE for patients with advanced HCC. Methods: Pts with advanced HCC who treated with Lenvatinib plus anti-PD1 and TACE were enrolled. Objective response rate (ORR), PFS, disease control rate (DCR) and OS were calculated to assess the antitumor response and the treatment-related adverse events to the safety. Consecutive pts were identified from September 2021 to August 2023.The Patients were included based on the following chief eligibility criteria. After signing the informed consent form, patients received sequential treatment with TACE in combination with Lenvatinib and tislelizumab. The anti-PD1 were recommended to be used continually every 3 weeks until disease progression, or intolerable toxicity. Lenvatinib was recommended to be used continually every day until disease progression, or intolerable toxicity. Follow up TACE should be given according to the patient's condition, no more than 3 times. Results: Between Sep. 2021 to Aug. 2023, 45 were enrolled. All pts received at least one dose of study treatment. The median age was 56 years(range34,73), 4 of the pts are BCLC-B stage, 41 of the pts are BCLC-C stage.Progression occurred in 8 of 45 patients and 14 patients died. The median PFS was 13.4 months (95% CI: 10.9-15.8 months) and the median OS was 20 months (95% CI: 9.8-30.4months). Of the 45 patients, a total of 3 (6.7%) patients achieved complete response (CR), and these 3 patients were treated with surgical resection. Partial Response (PR) was achieved in 12 patients (20%), Stable Disease (SD) in 22 pts (33.3%), Progressive Disease (PD) in 8 pts (17.8%), and Objective Response Rate (ORR) in patients. The Objective Response Rate (ORR) was 33.3% and the Disease Control Rate (DCR) was 82.2%.Treatment-related adverse events included increased AST 44.4%(20/45), increased ALT 51.1%(23), increased total bilirubin 42.2%(19/45), rash 44.4%(20/45), pruritus 42.2%(19/45), gastrointestinal reaction 33.3%(15/45), abdominal pain 24.4%(11/45), sensory abnormality 20%(9/45), and arthralgias 4.4%(2/45), etc., and Grade 3 Adverse events were increased ALT 2.2%(1/45), increased AST 4.4%(2/45), increased total bilirubin 2.2%(1/45), rash 2.2%(1/45), and gastrointestinal reaction 2.2%(1/45).No grade 4 or above adverse events occurred. Conclusions: In this study, TACE plus anti-PD1 and targeted therapies showed favorable efficacy and manageability in patients with advanced HCC. Toxicity was manageable with a low incidence of grade 3-4 adverse events. There were no unexpected safety signals.

State of the Art in Low-Grade Glioma Management: Insights From Isocitrate Dehydrogenase and Beyond.

Low-grade gliomas present a formidable challenge in neuro-oncology because of the challenges imposed by the blood-brain barrier, predilection for the young adult population, and propensity for recurrence. In the past two decades, the systematic examination of genomic alterations in adults and children with primary brain tumors has uncovered profound new insights into the pathogenesis of these tumors, resulting in more accurate tumor classification and prognostication. It also identified several common recurrent genomic alterations that now define specific brain tumor subtypes and have provided a new opportunity for molecularly targeted therapeutic intervention. Adult-type diffuse low-grade gliomas are frequently associated with mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), resulting in production of 2-hydroxyglutarate, an oncometabolite important for tumorigenesis. Recent studies of IDH inhibitors have yielded promising results in patients at early stages of disease with prolonged progression-free survival (PFS) and delayed time to radiation and chemotherapy. Pediatric-type gliomas have high rates of alterations in BRAF, including BRAF V600E point mutations or BRAF-KIAA1549 rearrangements. BRAF inhibitors, often combined with MEK inhibitors, have resulted in radiographic response and improved PFS in these patients. This article reviews emerging approaches to the treatment of low-grade gliomas, including a discussion of targeted therapies and how they integrate with the current treatment modalities of surgical resection, chemotherapy, and radiation.

Efficacy and safety assessment of drug-eluting bead transarterial chemoembolization combined with molecular targeted agents or immunotherapy in unresectable hepatocellullar carcinoma: Real-world evaluation.

e16164 Background: Drug-eluting bead transarterial chemoembolization (DEB-TACE) is established as a safe and effective treatment for advanced hepatocellular carcinoma (HCC). Recent advancements in molecular targeted agents and immunotherapy have led to exploration of combining DEB-TACE with tyrosine kinase inhibitors (TKIs) or immunotherapy. However, real-world evaluations of DEB-TACE in combination with TKIs or immunotherapy are limited. This study aimed to assess the efficacy and safety of DEB-TACE alone, DEB-TACE with TKIs, and DEB-TACE with TKIs and immunotherapy. Methods: This study retrospectively enrolled 124 patients with unresectable HCC treated at Peking University Cancer Hospital from April 2018 to April 2023. Patients were divided into three groups: DEB-TACE alone (DTACE, 45 patients), DEB-TACE plus TKI (DTACE+TKI, 51 patients), and DEB-TACE plus TKI and immunotherapy (DTACE+TKI+IM, 28 patients). Propensity score matching (PSM) was used to compare efficacy and safety between DTACE and DTACE+TKI. Primary endpoints were progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), disease control rate (DCR), assessed by RECIST Version 1.1. Adverse events were graded according to CTCAE version 5.0. Results: Among the patients, 99 were male and 25 were female, with 88.7% in BCLC-B or C stage. Before enrollment, 50.8% had received other treatments. In the DTACE+TKI+IM group, mPFS and mOS were higher compared to DTACE or DTACE+TKI alone (mPFS: 15.2 vs 9.2 for DTACE, 8.7 for DTACE+TKI; mOS: 32.3 vs 25.0 for DTACE, 20.9 for DTACE+TKI), though not statistically significant. ORR and DCR were 31.3% and 86.7% in DTACE, 35.3% and 84.3% in DTACE+TKI, and 39.3% and 96.4% in DTACE+TKI+IM, respectively. PSM analysis for DTACE and DTACE+TKI showed slightly better mPFS and mOS in DTACE+TKI (mPFS: 9.5 vs 9.2 months; mOS: 26.2 vs 19.4 months). No treatment-related deaths occurred, and serious adverse events (AEs) were comparable among the groups, with pain being the most common. AE. Notably, the frequency and severity of pain were closely related to the type of drug-eluting beads used, with the incidence of severe pain significantly lower in the HepaSphere DEB-TACE group compared to the CalliSphere or DCB group (0% versus 12.4% versus 19.7%, respectively; p &lt; 0.001). Conclusions: DEB-TACE has been demonstrated as a safe, feasible, and efficacious treatment option for patients with unresectable HCC. There is a notable trend towards prolonged progression-free survival (PFS) and overall survival (OS) when DEB-TACE is combined with TKIs and immunotherapy. Moreover, HepaSphere DEB-TACE shows a lower incidence of severe pain compared to other types of drug-eluting beads, further highlighting its potential advantages in managing HCC.

Efficacy and safety of eribulin-based chemotherapy in patients with advanced breast cancer: A single-centre retrospective study.

e13121 Background: Eribulin, a nontaxane microtubule dynamics inhibitor, which was approved for the third-line treatment of advanced breast cancer (ABC) in China in 2019. This retrospective study aimed to assess efficacy and safety of Eribulin-based chemotherapy in ABC patients, especially for patients exhibiting HER2-0 and HER2-low status (immunohistochemistry [IHC] 1+ or IHC 2+with a negative in situ hybridization assay). Methods: This single-center retrospective study planned to include 126 ABC patients from January 2020 to December 2023. Enrolled participants received Eribulin either as monotherapy or in combination with other regiments such as anti-angiogenic therapy, PD-1 inhibitor, or alternative chemotherapy in clinical practice. The primary outcomes included progression-free survival (PFS) and safety assessments. Results: A total of 84 patients with ABC received Eribulin were enrolled. Patients' baselines were summarized as follows: The median age was 53.3 years (range 30.0–86.0 years). 53 (63.1%) patients were HER2-low while 40 (47.6%) patients were hormone receptor (HR) positive. 63.1% patients have received at least one line chemotherapy before the use of Eribulin. According to the K-M survival analysis, the median PFS was 6.0 (range 3.2-11.3) months for all patients. The median PFS was longer for patients received aromatase inhibitors (AI) for over 6 months than patients with AI naive (median 10.1 vs 6.6 months; p=0.192) in HR positive patients. Patients who received CDK4/6 therapy had longer PFS than patients (median 10.7 vs 6.6 months; p=0.38). There was a trend toward prolonged PFS in the HER2-0 group compared with HER2-low group (median 10.13 vs 6.03 months; p=0.154), although there was no significant difference. A nonsignificant improvement of PFS was observed in HR-/HER2-0 patients, compare with HR-/HER2-low patients (median 16.4 vs 4.7mo; p=0.21). Meanwhile the median PFS of HER2-0 and HER2-Low was similar in HR positive patients. The objective response rate was 35.5% in HER2-0 group and 30.2% in HER2-low group. In multivariate cox regression, Eribulin as first line treatment (HR, 4.028; 95% CI, 1.131-14.337) and HER2-0 (HR, 2.903; 95% CI, 1.257-6.702) showed prognostic values regarding PFS. Common grade 3 or 4 adverse events that were reported in more than 10% were neutropenia (41.6%) and leukopenia (26.2%). No treatment-related deaths were reported. Conclusions: This single-center study demonstrated encouraging efficacy and safety in the ABC patients treated with Eribulin. Significant PFS benefit was associated with Eribulin treatment in patients with HER2-0 compared with HER2-low. This study still needs longer follow-up to evaluate its efficacy more comprehensively.

Immune phenotype profiling based on anatomic origin of melanoma and impact on clinical outcomes of immune checkpoint inhibitor treatment.

9569 Background: The inflamed immune phenotype is associated with a favorable response to immunotherapy in metastatic malignant melanoma. Although variations in molecular features across melanoma subtypes and differing ethnic distributions have been well reported, studies investigating immune phenotypes across multiple institutions within the context of different melanoma subtypes are scarce. We examined the association of immune phenotypes with outcomes after immunotherapy, based on subtypes of malignant melanoma. Methods: Two institutional advanced melanoma cohortsrepresenting Asian and Western populations (YUHS, n = 123; Stanford University, n = 102) were included. H&amp;E-stained tumor slides were assessed using Lunit SCOPE IO, an AI-powered whole slide image analyzer, to define the inflamed score (IS, % of inflamed area) and the inflamed phenotype (&gt;33.3% IS). Clinical outcomes after immune checkpoint inhibitor (anti-PD-1/PD-L1) treatment, including progression-free survival (PFS) and overall-survival (OS), were assessed. Results: In the overall cohort (n = 225), the inflamed phenotype was associated with prolonged PFS (HR = 0.634, 95% CI: 0.453 – 0.887, p = 0.007) and OS (HR = 0.655, 95% CI: 0.432 – 0.992, p = 0.044). On analysis of melanoma subtypes, we identified non-acral cutaneous melanomas (CM, n = 94), acral melanomas (AM, n = 52), mucosal melanomas (n = 43), uveal melanomas (n = 16), and melanomas of unknown primary site (n = 20), with a disproportionate enrichment of AM (37.4%) and mucosal (29.3%) melanoma cases in the YUHS cohort and CM cases (68.6%) in the Stanford cohort. The IS varied across different melanoma subtypes, with the highest IS observed in CM (median, [IQR]; 34.0, [5.8–52.2]), and significantly lower scores in AM (22.3, [7.7–36.9]), mucosal (13.6, [0–31.4]), and uveal melanoma (5.5, [0–13.6]). Among CM patients, the inflamed phenotype was significantly associated with better post-immunotherapy PFS (HR = 0.476, 95% CI: 0.274 – 0.826, p = 0.007). In contrast, the inflamed phenotype did not correlate with survival in AM patients (p = 0.58), who exhibited universally poorer PFS compared to non-AM patients (HR = 2.124, 95% CI: 1.486 - 3.005). Conclusions: AI-powered immune phenotype assessment highlights a heterogeneity of immune phenotypes across specific melanoma subtypes, as well as differential association with outcomes after immune checkpoint inhibitor treatment. While CM patients were well-stratified by immune phenotype, the predictive value of immune phenotyping was less pronounced in acral melanomas, which demonstrated poorer outcomes following immunotherapy.