Median Progression-free Survival Research Articles

Equecabtagene Autoleucel in Patients With Relapsed or Refractory Multiple Myeloma

ImportanceEquecabtagene autoleucel (eque-cel), a fully human-derived B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, has exhibited potential for the treatment of relapsed or refractory multiple myeloma (RRMM), and further investigation in a larger cohort is necessary.ObjectiveTo evaluate whether eque-cel can benefit patients with RRMM and determine the overall response rate postinfusion.Design, Setting, and ParticipantsThe FUMANBA-1 trial was a single-arm, open-label, phase 1b/2 trial that evaluated eque-cel in adult patients with RRMM. Enrollment began in April 2020, and patients who received eque-cel will be monitored for a minimum of 15 years following the infusion. As of September 2022, patients with heavily pretreated RRMM who received at least 3 prior courses of therapy from 14 centers were enrolled. Data were analyzed from April 2020 to September 2022.InterventionsPatients received a single infusion of eque-cel at 1.0 × 106 CAR-positive T cells/kg after the lymphodepletion.Main Outcomes and MeasuresEfficacy was the primary objective, and safety, pharmacokinetics, and pharmacodynamics were secondary objectives.ResultsOf 103 patients who received an eque-cel infusion, 55 (53.4%) were male, and the median (range) age was 58 (39-70) years. A total of 101 patients were evaluable for efficacy. At a median (range) follow-up of 13.8 (0.4-27.2) months, the overall response rate was 96.0% (97 of 101), with 74.3% (75 of 103) achieving a complete response or better. Among the 12 patients who had prior CAR T-cell treatment, 75% (9 of 12) achieved a response. The median progression-free survival was not reached, with a 12-month progression-free survival rate of 78.8% (95% CI, 68.6-86.0). A total of 96 patients (95.0%) achieved minimal residual disease negativity at a sensitivity threshold of 10−5. Adverse events were favorable: 96 of 103 patients (93.2%) experienced cytokine release syndrome (grade 1 to 2 in 95 patients [92.3%]) and 2 (1.9%) experienced immune effector cell–associated neurotoxicity syndrome (grade 1 to 2). All cases of immune effector cell–associated neurotoxicity syndrome and 94 of 96 cases of cytokine release syndrome resolved with treatment. Additionally, only 20 patients (19.4%) developed antidrug antibodies. Cellular kinetic analysis confirmed CAR-positive T cells in all patients, with the longest duration at 735 days.Conclusions and RelevanceIn this trial, eque-cel led to early, deep, and durable responses in patients with heavily pretreated RRMM with a manageable safety profile. Patients with prior CAR T-cell therapy also benefitted from eque-cel.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2000033946

Survival Outcomes of Patients with Primary Plasma Cell Leukemia in the Era of Proteasome Inhibitors and Immunomodulatory Agents: A Real-Life Multicenter Analysis.

In this study, we aimed to obtain real-life data on the use of antimyeloma agents, which significantly increase overall survival (OS) in multiple myeloma (MM) patients, in primary plasma cell leukemia (pPCL) patients with a poor prognosis. Data from 53 patients who were diagnosed with pPCL between 2011-2020 and who used at least one proteasome inhibitor (PI) and/or immunomodulatory (IMID) agent were analyzed retrospectively. Depending on the year of pPCL diagnosis, 20% leukocytes or ≥2×109/L plasma cells in the peripheral blood were used. The median age of the patients was 58 years, and 23 (43.4%) patients were over 65 years of age. For first-line treatment, PI or IMID alone was used in 31 (58.5%) patients, and PI and IMID were used simultaneously in 15 (28.3%) patients. Additionally, 21 (39.6%) patients received transplantation, and 13 (24.5%) patients received maintenance treatment. The median progression-free survival was 4 (1-42) months. When patients whose primary disease was refractory to first-line therapy were excluded, the duration of treatment was 6.5 months. The median OS was 15 months, with a median follow-up of 15 months. Only 7 (13.2%) of the patients were alive at the last follow-up visit. Those with higher beta-2 microglobulin levels and ISS stage 3 and nontransplant patients receiving first-line treatment had shorter OS (p=0.005, p=0.02 and p=0.008, respectively). Otherwise, the concomitant use of PIs and IMIDs, the addition of chemotherapy to induction therapy, and the response to induction therapy or maintenance therapy did not affect OS. In our study, as in previous similar studies, we could not see the increased survival trend in pPCL which is observed in MM. New studies are needed for pPCL patients, which is likely to increase with the new diagnostic criteria, based on current agents and information in MM.

Efficacy and safety of tyrosine kinase inhibitors with thoracic radiotherapy for patients with oncogene-mutated non-small cell lung cancer: a meta-analysis.

Tyrosine Kinase Inhibitors (TKIs) is an important therapy for patients with oncogene-mutated Non-Small Cell Lung Cancer (NSCLC). However, acquired resistance remains a major challenge. The efficacy of TKIs plus thoracic radiotherapy (RT) in oncogene-mutated NSCLC patients is uncertain. Therefore, we performed a meta-analysis to comprehensively evaluate the efficacy and safety of thoracic RT plus TKIs in oncogene-mutated NSCLC patients. The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane Library. Studies comparing the efficacy and safety of TKIs plus RT with TKIs alone in oncogene-mutated NSCLC patients were included in this analysis. Outcomes were median progression-free survival (mPFS), median overall survival (mOS), and incidence of adverse events (AEs). This analysis performed a subgroup analysis of the efficacy of first-line TKIs in combination with RT. This meta-analysis included 12 studies with 2936 patients (n = 823 patients with TKIs plus thoracic RT, n = 2113 patients with TKIs alone). The results showed that patients who received treatment with TKIs plus thoracic RT were associated with superior mPFS and mOS than those who were treated with TKIs alone (hazard ratio [HR]: 0.42, 95% CI 0.30-0.59, p < 0.00001; HR: 0.56, 95% CI 0.41-0.70, p < 0.00001, respectively). Subgroup analyses showed that TKIs plus thoracic RT as first-line treatment was associated with better mPFS and OS (HR: 0.37, 95% CI 0.26-0.52, p < 0.00001; HR: 0.47, 95% CI 0.31-0.70, p = 0.0002, respectively). Although the combination of TKIs with thoracic RT was associated with an increased risk of total AEs (odds ratio [OR]: 1.17, 95% CI 1.06-1.29, P = 0.002), there was no significant difference in serious AEs (grade ≥ 3) (OR: 1.06, 95% CI 0.58-1.92, P = 0.86). The most frequently occurring radiation-related AEs were radiation pneumonitis, radiation esophagitis, and radiation dermatitis, with overall rates of 41.3%, 15.4%, and 11.1%, respectively. The incidence of severe radiation pneumonitis and radiation esophagitis was 4.5% and 6.2%, respectively. In comparison to TKIs alone, TKIs plus thoracic RT are associated with survival benefits, especially as a first-line treatment option. Although TKIs plus thoracic RT may increase the risk of total AEs, it did not increase the risk of severe AEs. Therefore, TKIs plus thoracic RT may be a promising therapeutic regimen for oncogene-mutated NSCLC patients.

Efficacy of disitamab vedotin in non-small cell lung cancer with HER2 alterations: a multicenter, retrospective real-world study

BackgroundNon-small cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER2) alterations poses a substantial treatment challenge. Current HER2-targeted therapies offer limited efficacy. Antibody-drug conjugates (ADCs) targeting HER2 have emerged as a promising therapeutic strategy. This study aimed to evaluate the clinical response to a novel ADC drug Disitamab vedotin (RC48) in advanced NSCLC with HER2 alterations.MethodsThis study conducted a retrospective review of patients harboring HER2 alterations treated with RC48 in the real world. Clinical outcomes were evaluated in terms of objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS).ResultsOut of 22 patients, 21 (95.5%) received RC48 combination therapy, while one received RC48 monotherapy. The ORR of all patients reached 45.5%, and the DCR stood at 90.9%. The median PFS (mPFS) was 7.5 months. Among patients receiving RC48 combination therapy, the ORR was 47.7%, and the mPFS of 8.1 months. The combination of RC48 with platinum+/- bevacizumab resulted in the highest ORR of 71.4% (5 out of 7 patients), with HER2 TKI following at a 50.0% ORR (4 out of 8 patients). First-line (1L) treatment with RC48 showed an ORR of 62.5% (5 out of 8 patients), second-line (2L) treatments had a 57.1% ORR (4 out of 7 patients), and beyond second-line (&amp;gt;2L) treatments exhibited a 14.3% ORR (1 out of 7 patients). Patients with 1L, 2L, or &amp;gt;2L treatment had a mPFS of 8.1 months, 7.2 months, and 7.4 months, respectively. Patients with HER2 mutations or amplifications, and those with concurrent mutations and amplifications at baseline, showed mPFS of 8.1 months, 9.4 months, and 7.4 months, respectively. The mPFS was significantly longer in patients with HER2 amplification. The most common adverse events included hand-foot syndrome (54.5%), asthenia (50.0%), decreased white blood cell count (45.5%), and liver impairment (45.5%). Grade 3 adverse events occurred in one (4.5%) patient.ConclusionRC48, particularly in combination regimens, demonstrates promising efficacy in advanced NSCLC with HER2 alterations. These findings underscore the need for further research to validate RC48’s application in clinical practice.

Peptide Receptor Radionuclide Therapy Improves Survival in Patients Who Progress After Resection of Gastroenteropancreatic Neuroendocrine Tumors.

Peptide receptor radionuclide therapy (PRRT) is an effective treatment for advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). We investigated a 2-decade experience with PRRT to determine whether PRRT confers a survival advantage to patients who progress after surgery versus other therapies. We identified patients from our clinic who had resection/cytoreduction of GEP-NETs, then disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The Kaplan-Meier method assessed progression-free survival (PFS) and overall survival (OS), calculated from progression after surgery (no-PRRT group) or the start of PRRT. Cox regression with time-dependent covariates controlled for immortal time bias and other confounders. Overall, 237 patients progressed after surgery; 95 received PRRT and 142 did not. No differences existed in sex, T or Nstage, tumor grade/differentiation, primary site, or time to progression; 94% of PRRT patients had metastases at diagnosis versus 77% in the no-PRRT group. Median PFS was longer in the PRRT group versus the no-PRRT group (32.4 vs. 11.0 months, p<0.001), as was median OS (49.8 vs. 38.4 months; p=0.009). In subgroup analysis, the PRRT group had improved PFS in small bowel NETs and pancreatic NETs. Time-dependent covariate analysis revealed a lower risk of death associated with PRRT (hazard ratio 0.61, p=0.028) after adjusting for sex, age, Mstage, tumor grade, and primary site. Surgical resection and cytoreduction is an effective treatment for patients with GEP-NETs, but most patients with metastatic disease develop recurrent disease. Surgery followed by PRRT after progression conferred superior PFS and OS over no PRRT/other therapies, and is an effective strategy for managing patients with GEP-NETs.

Effect of body mass index on immune checkpoint inhibitor efficacy in patients with advanced cancer.

The need for predictive factors regarding the response to immune checkpoint inhibitors (ICIs) is increasing. Recent research indicates that an enhanced response to ICIs is associated with a higher body mass index (BMI). This study aims to evaluate the relationship between response to ICIs and BMI in solid tumors. We retrospectively analyzed patients with advanced cancer treated with ICIs at one academic center. We compared the treatment responses of patients classified as underweight/normal weight (BMI <25) and overweight/obese (BMI ⩾ 25) according to their BMI at the initiation of ICI treatment. After excluding underweight patients, we also compared the progression-free survival (PFS) and overall survival (OS) of normal-weight, overweight, and obese patients. Overall, 113 patients were evaluated. Forty-seven (41.6%) patients had BMI <25 and 66 (58.4%) patients had a BMI ⩾ 25. In underweight/normal patients, median PFS was 7.7 months (95% CI: 4.7-10.6) while it was 8.0 months (95% CI: 4.1-11.9) in overweight/obese patients (HR 1.16, 95% CI: (0.76-1.75), p=0.477). In underweight/normal patients, the median OS was 21.7 months (95% CI: 11.6-31.7) compared to 18.7 months (95% CI: 12.7-24.6) in overweight/obese patients (HR 1.06, 95% CI: (0.69-1.64), p=0.774). The objective response rate (ORR) was 38.3% in underweight/normal patients and 34.8% in overweight/obese patients (p = 0.707). After excluding underweight patients, there were also no significant differences in PFS (p = 0.914), OS (p = 0.642), and ORR (p = 0.909) between patients of normal weight, overweight, and obesity. Our research found no correlation between BMI and response to ICIs. Additional prospective studies are necessary to assess the effect of BMI on the response to ICIs.

Association of artificial intelligence-based immunoscore with the efficacy of chemoimmunotherapy in patients with advanced non-squamous non-small cell lung cancer: a multicentre retrospective study

PurposeCurrently, chemoimmunotherapy is effective only in a subset of patients with advanced non-squamous non-small cell lung cancer. Robust biomarkers for predicting the efficacy of chemoimmunotherapy would be useful to identify patients who would benefit from chemoimmunotherapy. The primary objective of our study was to develop an artificial intelligence-based immunoscore and to evaluate the value of patho-immunoscore in predicting clinical outcomes in patients with advanced non-squamous non-small cell lung cancer (NSCLC).MethodsWe have developed an artificial intelligence–powered immunoscore analyzer based on 1,333 whole-slide images from TCGA-LUAD. The predictive efficacy of the model was further validated in the CPTAC-LUAD cohort and the biomarker cohort of the ORIENT-11 study, a randomized, double-blind, phase 3 study. Finally, the clinical significance of the patho-immunoscore was evaluated using the ORIENT-11 study cohort.ResultsOur immunoscore analyzer achieved good accuracy in all the three cohort mentioned above (TCGA-LUAD, mean AUC: 0.783; ORIENT-11 cohort, AUC: 0.741; CPTAC-LUAD cohort, AUC: 0.769). In the 259 patients treated with chemoimmunotherapy, those with high patho-immunoscore (n = 146) showed significantly longer median progression-free survival than those with low patho-immunoscore (n = 113) (13.8 months vs 7.13 months, hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.38 – 0.73; p &amp;lt; 0.001). In contrast, no significant difference was observed in patients who were treated with chemotherapy only (5.07 months vs 5.07 months, HR: 1.04, 95% CI: 0.71 – 1.54; p = 0.83). Similar trends were observed in overall survival.ConclusionOur study indicates that AI-powered immunoscore applied on LUAD digital slides can serve as a biomarker for survival outcomes in patients with advanced non-squamous NSCLC who received chemoimmunotherapy. This methodology could be applied to other cancers and facilitate cancer immunotherapy.

Busulfan and cyclophosphamide for autologous stem cell transplantation in patients with multiple myeloma after proteasome inhibitor and/or immunomodulatory drug treatment.

High-dose melphalan at 200mg/m2 (MEL-200) is the standard conditioning regimen before autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Busulfan (BU) and cyclophosphamide (CY) can be used as alternatives when MEL is unavailable. However, most studies on BU/CY conditioning regimens were conducted before proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) were available. This non-interventional comparative cohort study compared progression-free survival (PFS) between the MEL-200 and BU/CY in patients with MM treated with PIs and/or IMIDs. A total of 137 patients were analyzed (MEL-200,113 patients; BU/CY, 24 patients). The BU/CY group had a higher rate of PI and/or IMID use and very good partial response (VGPR) or complete remission (CR) at ASCT and post-ASCT maintenance. Median PFS was 29.7 and 46.8months in the MEL-200 and BU/CY groups, respectively. In the multivariate analysis, PFS was significantly better in the BU/CY group. International Staging System Stage I and VGPR or CR at ASCT were significantly associated with longer PFS. No treatment-related mortality was observed in either group by day 100. The BU/CY conditioning regimen may be a viable alternative to the MEL-200 regimen in patients with MM who undergo ASCT after treatment with PIs and/or IMIDs.

Efficacy, safety, and biomarker analysis of TACE combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma: a real-world study

BackgroundThe integration of transarterial chemoembolization (TACE) with systemic therapy has demonstrated improved survival outcomes in patients with unresectable hepatocellular carcinoma (HCC). However, there is limited evidence evaluating the combination of TACE with the systemic regimen of anti-PD-1/L1 inhibitor plus lenvatinib. This study aims to assess the efficacy and safety of TACE combined with lenvatinib and sintilimab in unresectable HCC patients.MethodsUnresectable HCC patients who received TACE in combination with sintilimab plus Lenvatinib as first-line treatment from 1 January 2020 to 31 March 2023 were included for the analysis. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were evaluated by modified Response Evaluation Criteria in Solid Tumors criteria. Exploratory biomarker analysis was conducted.ResultsThe study included 70 patients with unresectable HCC, predominantly male and infected with Hepatitis B. The median follow-up duration for the whole cohort was 13.8 months (95% CI 11.08–16.7). The ORR was 61.4% (95% CI, 49.0%–72.8%) and the DCR was 68.6% (95%CI, 56.4%–79.2%). The median PFS was 13.2 months (95% CI 11.0-NA), with a corresponding 1-year PFS rate of 50.3% (95% CI 39.7%-65.5%). The median OS was not reached, and the 1-year OS rate was 89.3% (95% CI 81.4%–97.9%). The most common treatment-related adverse events (TRAEs) were fatigue 38.6% (27/70), hypertension 32.9% (23/70), and hand-foot syndrome 31.4% (22/70). Most TRAEs were mild-to-moderate and manageable. In addition, significant predictive value was found in alpha-fetoprotein levels (AFP), with patients showing a level of decrease post-treatment having better PFS.ConclusionThe combination regimen demonstrated promising efficacy in treating unresectable HCC, accompanied by manageable safety profiles. Furthermore, the results of this investigation suggest that AFP holds promise as predictive biomarkers for this treatment strategy.

Six-year follow-up of phase II study exploring chemo-free treatment association with idelalisib and obinutuzumab in symptomatic relapsed/ refractory patients with Waldenström's macroglobulinemia.

We present the 6-year update of a phase 2 study evaluating the combination of obinutuzumab and idelalisib in relapse/refractory Waldenstrom macroglobulinemia. The results of the REMODEL trial demonstrated interesting efficacy in a high-risk genotype profile population. The primary endpoint was achieved with a median PFS of 25.4months (95% CI, 15.7 to 29.0). However, a major limitation of idelalisib is its toxicity. With a median follow-up of 70.9months, median OS was still not reached, and 5-year OS was 72.9% (95% CI, 61.3 to 86.6). We confirm that CXCR4 mutations had no impact on PFS or OS. However, TP53 mutated patients had shorter OS. At the time of analysis, six patients are alive without relapse and 40 had progressive disease. Among the 38 patients who received a new treatment, the median time to second progression was not reached in ibrutinib treated patients (n = 17) versus 30.8months in patients treated with other options (95% CI, 16.9 to NA), p = 0.005. With longer follow-up our prospective study is the first to show an impact of TP53 mutations in patients treated with fixed duration chemo-free regimen leading to a significant shorter OS in this population. Moreover, ibrutinib remains an effective treatment after this combination. This study was registered on the clinicaltrial.gov web (NCT02962401, November 9, 2016).

Efficacy of rechallenge after first-line immunotherapy for advanced gastric cancer: A retrospective real-world study

ABSTRACT We aimed to explore the efficacy of rechallenge after first-line immunotherapy in advanced gastric cancer (AGC) and to analyze the factors affecting prognosis based on clinical characteristics. Eighty-five AGC patients who underwent rechallenged after the failure of first-line treatment with immune checkpoint inhibitors (ICIs) were retrospectively collected from July 2019 to December 2022 in Jiangsu Cancer Hospital. Potential factors affecting prognosis were analyzed by univariate and multivariate Cox analysis. Survival analysis was performed by Kaplan–Meier method and Log rank test. Stratified factors included human epidermal growth factor receptor 2 (HER-2) and programmed cell death-ligand 1 combined positive score (PD-L1 CPS). The objective response rate (ORR) was 15.3%, and the disease control rate (DCR) was 74.1%. The median progression-free survival (PFS) was 4.8 months. Results showed that patients in the I + C group had the best response. The ORR was 20.0% VS 8.7% in the I + C group and I + C + AAD group. The DCR was 78.0% VS 65.2%, and the median PFS was 6.7 VS 4.7 months [hazard ratio (HR): 0.55, 95% confidence interval (CI): 0.30–1.00, p = .022]. The ORR was 20.0% VS 8.3% in the I + C group and I + C + ADC group. The DCR was 78.0% VS 75.0%, and the median PFS was 6.7 VS 4.4 months (HR: 0.59, 95%CI: 0.26–1.30, p = .112). The median PFS was 4.7 VS 4.4 months in the I + C + AAD group and I + C + ADC group (HR: 1.21, 95%CI: 0.60–2.47, p = .580). Adverse events (AEs) were found in 34 patients, mainly including leukopenia 9 (10.6%), and neutropenia 8 (9.4%). The incidence of grade 3–4 AEs was 8.2%. There were no drug-related deaths and all AEs were manageable. Rechallenge after first-line immunotherapy showed good survival benefit and acceptable safety in the therapy of AGC. Especially for patients with HER-2-positive and PD-L1 CPS ≥ 1%, rechallenge may be an effective treatment modality.

Clinical Benefits of Photodynamic Therapy Using Talaporfin Sodium in Patients With Isocitrate Dehydrogenase-Wildtype Diagnosed Glioblastoma: A Retrospective Study of 100 Cases.

Photodynamic therapy (PDT) with talaporfin sodium is an intraoperative local therapy administered after the surgical removal of malignant gliomas. However, its clinical efficacy in a large patient population has not been determined. To analyze the clinical outcomes and prognosis in isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients treated with PDT. This retrospective study included patients with newly diagnosed IDH-wildtype glioblastoma treated at Kobe University Hospital between January 2013 and December 2022. PDT involves irradiation of the resection cavity with a 664-nm semiconductor laser after an intravenous infusion of talaporfin sodium. The main outcome measures were the recurrence patterns and survival times, which were compared between the PDT and non-PDT groups. Univariate and multivariate analyses were used to determine the prognostic factors. In addition, adverse events and prognostic factors in the PDT group were analyzed. A total of 44 and 56 patients were included in the PDT and non-PDT groups, respectively. The local recurrence rate was significantly lower in the PDT group than in the non-PDT group (51.3% vs 83.9%), whereas the distant recurrence and dissemination rates were significantly higher in the PDT group than in the non-PDT group (48.7% vs 16.1%). Two grade 3 adverse events were observed in the PDT group. The median progression-free survival and overall survival times were significantly longer in the PDT group than in the non-PDT group (progression-free survival: 10.8 vs 9.3 months, respectively, and overall survival: 24.6 vs 17.6 months, respectively). Multivariate analysis of the PDT groups revealed that younger age was an independent prognostic factor. PDT with talaporfin sodium provided effective local control with minimal adverse effects. The survival time of the patients treated with PDT was significantly longer than that of the patients who did not receive PDT. Therefore, a randomized controlled clinical trial on PDT is warranted.

First-in-human, phase 1 dose-escalation and dose-expansion study of a RET inhibitor SY-5007 in patients with advanced RET-altered solid tumors

Oncogenic RET alteration is an important, tissue-agnostic therapeutic target across diverse cancers. We conducted a first-in-human phase 1 study on SY-5007, a potent and selective RET inhibitor, in patients with RET-altered solid tumors. Primary endpoints were safety, maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D). Secondary endpoints included pharmacokinetics and preliminary anti-tumor activity. A total of 122 patients were enrolled (17 in dose-escalation phase and 105 in dose-expansion phase), including 91 with non-small cell lung cancer, 23 with medullary thyroid cancer, 7 with papillary thyroid cancer and 1 with gastric cancer. Treatment-related adverse events (TRAEs) were reported in 96.7% of patients, with the most common grade ≥ 3 TRAEs being hypertension (22.1%), diarrhea (16.4%), hypertriglyceridemia (6.6%), and neutropenia (6.6%). The exposure to SY-5007 was dose proportional. Among the 116 efficacy-evaluable patients, the overall objective response rate (ORR) was 57.8%, with 70.0% in treatment-naïve patients and 51.3% in previously treated patients. The median progression-free survival (PFS) was 21.1 months. Efficacy was observed regardless of tumor types and previous therapies. Biomarker analysis of 61 patients with circulating tumor DNA (ctDNA)-detectable RET alterations showed an ORR of 57.4% and median PFS of 13.8 months. Rapid ctDNA clearance of RET alteration correlated with faster responses and improved outcomes. In relapsed patients, off-target induced resistance was observed in 57.1% (12/21), with no on-target RET alterations identified. In conclusion, SY-5007 was well-tolerated and showed promising efficacy in patients with RET-altered solid tumors. Serial ctDNA monitoring may unveil treatment response and potential resistance mechanisms (NCT05278364).

Durvalumab Following Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Differences in Survival Based on Age and Post-Progression Systemic Therapy.

Concurrent chemoradiotherapy (cCRT) followed by 1 year of the immune checkpoint inhibitor (ICI) durvalumab is standard of care for patients with unresectable stage III nonsmall cell lung cancer (NSCLC). The purpose of this study was to evaluate survival outcomes of (1) cCRT followed by durvalumab in patients older versus younger than 75 years of age and (2) post-progression treatment with ICI alone versus chemotherapy alone versus combined ICI and chemotherapy. Patients with unresectable stage III NSCLC treated between January 2018 and July 2023 with cCRT followed by durvalumab were identified retrospectively. Progression-free survival (PFS) and overall survival (OS) from ICI start were analyzed in three cohorts aged < 65, 65-74, and ≥ 75 years. Multivariable Cox proportional hazard regression modelling of factors associated with OS was undertaken. Logistic regression analysis identified risk factors of early durvalumab discontinuation for toxicity. Time from first salvage drug treatment to death (OS-2) was described. A total of 472 patients were analyzed: the proportions aged < 65, 65-74, and ≥ 75 years were 34.3%, 42.8%, and 22.9%, respectively. Odds of early durvalumab discontinuation was 2.2-fold greater in the oldest (versus youngest) cohort. Age associated differences in median PFS (26.7months, 20.3months, and 14.2months; p< 0.001) and OS (60.8months, 44.4 months, and 27.6 months; p< 0.001) were observed. On multivariable analysis, factors associated with shorter OS were age ≥ 75years (versus < 65), performance status 2/3 (versus 0/1), stage IIIC (versus IIIA), neutrophil to lymphocyte ratio (per 7.43 unit increase), Charlson comorbidity index (per 1 unit increase), tumoral PD-L1 expression < 1% (versus ≥ 50%, 1-49%, or unknown), and squamous histology (versus non-squamous). Of 264 patients with disease progression, 48.5% received subsequent drug therapy. Median OS-2 was longer with ICI alone (9.9 months) or ICI-chemotherapy (11.8 months) than platinum doublet chemotherapy (6.7 months.) For recurrences < 6 months from the last durvalumab infusion, OS-2 were similar across treatment groups. In the studied cohort, OS was significantly shorter for patients ≥ 75 years of age treated with cCRT followed by durvalumab compared to those < 65 years. Post-progression systemic therapy was associated with modest efficacy, underscoring the need for new therapies.

Pegylated liposomal doxorubicin in partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer: a prospective study.

This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) for patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer. Patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer were recruited in this prospective, open-label, single-arm, multicenter study. Eligible patients were given 4-6 cycles of PLD (40mg/m2 on day 1, every 4 weeks). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life, and safety. Exploratory endpoints included the change trend of CA125 and platinum-free interval. Between June 2017 and November 2020, 167 eligible patients were included in the full analysis set. The median PFS and OS were 6.8 months (95% CI, 4.4-9.3 months) and 19.1 months (95% CI, 15.0-23.3 months), respectively. The ORR and DCR were 32.3% and 60.5%, respectively. The ORR (62.3 vs 22.5%) and DCR (84.9 vs 60.7%) of patients with a CA125 decrease after the first cycle were significantly higher than those without a CA125 decrease (all P < .05). Grade ≥ 3 and serious adverse events were reported in 9.9% and 3.9% of patients, respectively. No treatment-related death was observed. PLD showed promising efficacy and manageable tolerability in patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer.ClinicalTrials.gov Identifier: Chinese Clinical Trial Registry, ChiCTR1900022962.

Efficacy and tolerance of short cycles of palliative radiotherapy in advanced anal sac adenocarcinomas in dogs

Successful management of advanced anal sac gland adenocarcinomas (AGASACA) often requires a multimodal approach. In recent years the role of palliative radiotherapy (pRT) has become increasingly more important, mainly in dogs with severe local clinical signs. This study describes efficacy and tolerance of short cycles of pRT. Retrospective single-institution study including dogs with AGASACA treated with at least one short cycle of pRT (IMRT, 4Gy BID for two consecutive days). All dogs were staged with CT and followed to death. Outcome measures were PFS and OST from the first pRT. Potential prognostic factors were evaluated. Twelve dogs were included (one stage II, four stage III, seven stage IV). Three dogs had one cycle, seven had two cycles, and two had three cycles of pRT. All dogs experienced a clinical benefit after pRT. One dog also had surgery, four systemic treatment, and five both. Eleven dogs died during the follow-up (four for local progression, six for systemic progression, one unknown). The median PFS was 198 days (95% CI 98—298) and the OST was 250 days (95% CI 124—376). Mild, acute, short-term GI toxicity occurred in seven dogs (five G1; two G2). None of the dogs experienced clinically relevant late toxicity. Short cycles of radiotherapy can be effectively used as a palliative treatment for advanced AGASACA with minimal toxicity. The small number of patients did not allow to assess the benefits of combining RT with other treatment modalities or the identification of meaningful prognostic factors.

Efficacy and safety of immune checkpoint inhibitors combined with chemotherapy or tyrosine kinase inhibitors in advanced endometrial cancer: A systematic review and meta-analysis.

The objective of this meta-analysis was to conduct a comprehensive assessment of the therapeutic effectiveness and safety profile of the combination of immune checkpoint inhibitors (ICIs) with either chemotherapy or tyrosine kinase inhibitors (TKIs) in the treatment of advanced-stage endometrial cancer (EC). This meta-analysis conducted a thorough literature search across PubMed, Cochrane Library, Embase, and Web of Science databases from their earliest records up to November 18th, 2023, identifying qualified randomized controlled trials (RCTs), cohort studies, and single-arm trials for inclusion in the analysis. The meta-analysis were performed to quantify and analyzed the evidence from the existing literature, focusing on outcomes including the objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), progression-free survival (PFS), and adverse events (AE). A total of 13 studies were included. In terms of ICI combined with chemotherapy, the single-arm trials showed that ICI combined with chemotherapy was effective in improving the ORR, but the overall rate of AE was higher. The results based on RCT suggested that ICI combined with chemotherapy resulted in a longer PFS of 12-24 months and OS of 18-month compared to the control group in advanced EC. In terms of ICI combined with TKI, the pooled ORR was 39.0%, the pooled DCR was 79.9%, the pooled OS rate was 50.4%, and the pooled overall AE rate was 95.8%, the pooled grade ≥3 AE rate was 73.8%, the pooled median progression-free survival (mPFS) was 6.126 months, and pooled OS was 15.099 months in advanced EC. The integrative therapeutic approach combining (ICIs) with chemotherapy or (TKIs demonstrates notable clinical efficacy in advanced EC, which can prolong the survival and help to disease control. Nevertheless, it is imperative for clinicians to be vigilant regarding the potential for adverse reactions to emerge. In addition, more RCTs are needed to solidify this study's efficacy and safety further.

Evolution of treatment strategies for solid tumors with RET rearrangement in China and real-world treatment status of Non-small Cell Lung Cancer (NSCLC)

ObjectiveThe present study endeavors to furnish an exhaustive review of the research advancements on solid tumors harboring RET rearrangement within the Chinese context, particularly emphasizing the examination of real-world therapeutic strategies and clinical outcomes observed in individuals diagnosed with advanced non-small cell lung cancer (NSCLC). The review delves into a critical assessment of the therapeutic efficacy of targeted RET inhibitors, while also scrutinizing the diverse array of treatment modalities employed in the Chinese patient population.MethodsThe study conducted a comprehensive review of the advancements made by Chinese scholars in the realm of RET driver genes. It delved into the analysis of the incidence of RET rearrangements in solid tumors, alongside an examination of the varied treatment paradigms and their current status within China. Utilizing the RECIST 1.1 criteria, the study evaluated the therapeutic efficacy achieved in RET-positive NSCLC patients undergoing diverse treatment modalities. Furthermore, treatment-related adverse events (TRAEs) were meticulously graded following the Common Terminology Criteria for Adverse Events (CTCAE).ResultsA retrospective, multi-center, real-world analysis was conducted, encompassing 64 patients diagnosed with pathologically confirmed RET rearrangement advanced non-small cell lung cancer (NSCLC) between December 2015 and November 2023. Notably, KIF5B-RET emerged as the most prevalent RET fusion partner, accounting for 59.4% of cases. Therapeutic interventions among these patients included specific targeted inhibitors such as Pralsetinib (48.4%), chemotherapy (34.3%), multi-target inhibitors (15.6%), and one case (1.6%) involving immunotherapy combined with anti-angiogenic therapy. In terms of progression-free survival (PFS), Pralsetinib monotherapy demonstrated a median PFS of 16.03 months, outperforming chemotherapy (2.87 months; p < 0.0001), chemotherapy combined with anti-angiogenic therapy (6.90 months; p = 0.048), and multi-target inhibitors (2.50 months; p < 0.0001). Furthermore, the one-year and two-year overall survival (OS) rates for Pralsetinib monotherapy were 64.3% and 46.4%, respectively. Regarding safety, 71.0% of patients receiving Pralsetinib experienced at least one adverse event, with 45.2% classified as grade 3–4 in severity. Notably, no fatalities were attributed to adverse events. Common adverse events included hemoglobin reduction (35.5%) and neutropenia (32.3%), indicative of an overall favorable safety profile for Pralsetinib in this patient population.ConclusionThis study encapsulates the research endeavors and treatment advancements of RET rearrangement solid tumors within the Chinese healthcare landscape, specifically highlighting the diverse real-world therapeutic approaches and their effectiveness in managing advanced RET rearrangement NSCLC among Chinese patients. Notably, targeted RET inhibitors like Pralsetinib have emerged as potent therapeutic agents, exhibiting remarkable efficacy and a manageable safety profile in this patient cohort. These findings underscore the potential of Pralsetinib and similar targeted therapies as novel treatment options for individuals with RET fusion-positive NSCLC.

Camrelizumab combined with gemcitabine and apatinib in treating advanced PD-L1-positive biliary tract cancers.

The efficacy of combined chemotherapy and immunotherapy has previously been demonstrated in patients with biliary tract cancer. The aim of this study was to assess the efficacy and safety of camrelizumab in combination with gemcitabine and apatinib as a first- or second-line treatment for advanced programmed death-ligand 1 (PD-L1)-positive biliary tract cancer. This prospective, single-arm, and exploratory clinical trial aimed at recruiting 20 PD-L1-positive patients (tumor proportion score ≥1% or combined positive score ≥1) who met the inclusion criteria. Camrelizumab (200 mg) was administered in combination with gemcitabine (800 mg/m2) and apatinib (250 mg). The primary endpoint was the objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Fourteen patients were enrolled between September 2, 2020, and December 15, 2022. At the data cutoff on August 16, 2023, the median follow-up time was 11.4 months (interquartile range, 4.5-15.4), with one patient still undergoing treatment. Among the enrolled patients, six achieved a partial response, and four had stable disease. The ORR was 42.9% (95% confidence interval [CI], 17.7-71.1), and the DCR was 71.4% (95% CI, 41.9-91.6). The median PFS was 5.4 months (95% CI, 2.8-not reached), and the median OS was 13.5 months (95% CI, 5.7-not reached). The most frequent grade 3 or 4 treatment-related adverse event was neutropenia (n = 4, 29%). The combination of camrelizumab, gemcitabine, and apatinib showed promising efficacy and acceptable safety in patients with advanced PD-L1-positive biliary tract cancer.

Efficacy of Paclitaxel and Cetuximab in Recurrent/Metastatic Oral Cancer Cases Following Superselective Intraarterial Chemoradiotherapy: A Retrospective Cohort Study.

The therapeutic efficacy of the paclitaxel (PTX) + cetuximab (Cmab) combination regimen was investigated in patients with recurrence or metastasis after superselective intraarterial chemoradiotherapy (SSIACRT) for oral cancer, and the safety was retrospectively examined. All enrolled patients with advanced oral cancer or who had refused surgery over 10 years from December 2012 to December 2022 underwent SSIACRT for 6 to 9 weeks [cisplatin (CDDP): total 160-630 mg/m2and radiotherapy: total 50-70 Gy]. Nine cases (tongue cancer, maxillary gingival cancer, and mandibular gingival cancer; three cases each) were subjected to PTX + Cmab therapy. Recurrence or metastases were observed within six months after the onset of treatment, complicating the conduct of salvage surgery. Cmab (first dose: 400 mg/m2and second and following doses: 250 mg/m2) and PTX (80 mg/m2) were administered weekly. The overall response rate was 44.4% (four of nine cases), and the disease control rate was 88.9% (eight of nine cases), whereas the median progression-free survival was seven months, and the overall survival was 11 months. Grade 3-4 adverse events were neutropenia in 33.3% of the cases, leukopenia in 55.6%, anemia in 22.2%, and acneiform skin rash in 22.2%. Based on the above, PTX + Cmab therapy for recurrent and metastatic cases after SSIACRT had comparable results to other second-line modalities and enabled to cope with the side effects of myelosuppression. PTX + Cmab therapy may be an effective treatment mode for recurrent or metastatic head and neck cancer resistant to CDDP after SSIACRT treatment.