Cancer vaccines: can they improve survival?

A large number of different clinically acceptable and equivalent regimens for treatment of recurrent ovarian cancer have been identified. There is insufficient evidence to indicate that any one drug or regimen used for retreatment is superior to any other. In vitro chemoresponse assays have been investigated for informing effective treatment selection for recurrent ovarian cancer. The value of these assays to yield useful clinical information has been a subject of considerable debate among oncologists because of lack of information from well-controlled prospective trials and conflicting data from retrospective trials. This prospective, multicenter, clinical trial evaluated the use of a chemoresponse assay to improve clinical outcomes in patients with recurrent ovarian cancer. Patients with persistent or recurrent ovarian cancer were enrolled at 35 sites across the United States under an institutional review board–approved protocol. Viable tumor tissue samples were collected for the chemoresponse assay. Patients received 1 of 15 protocol-designated treatments empirically chosen by oncologists blinded to the assay results. The in vitro response of each treatment was classified as sensitive (S), intermediate (I), or resistant (R). The primary study endpoint was progression-free survival (PFS); overall survival (OS) was the secondary endpoint. Associations of the in vitro response for each treatment with PFS and OS were analyzed. Between 2004 and 2011, a total of 262 eligible patients were enrolled. The patients treated with an assay-sensitive regimen had significantly improved PFS and OS compared with those treated with an assay-resistant regimen; there was no difference in these outcomes between the I and R groups. With univariate analysis, the median PFS was 8.8 months for S versus 5.9 months for I + R; the hazard ratio (HR) was 0.67, P = 0.009. Multivariate analysis showed that the association with the in vitro response was consistent within platinum-sensitive and platinum-resistant subpopulations (HR, 0.71 vs 0.66, respectively) and was independent of other covariates (P = 0.020). There was also a significant 14-month improvement in mean OS (37.5 months for S vs 23.9 months for I + R; HR, 0.61; P = 0.010). The findings of this prospective study show significant improvement in both PFS and OS among patients with either platinum-sensitive or platinum-resistant recurrent ovarian cancer when they are treated with assay-sensitive agents. Improvements in PFS and OS were both greater than 50%. This study is the first prospective clinical trial of this design conducted.

3502 Background: Regorafenib (REG) is an oral multi-kinase inhibitor. The CORRECT trial was conducted to evaluate REG in patients (pts) with mCRC who had progressed after all approved standard therapies. Methods: Enrollment criteria included documented mCRC and progression during or ≤3 months after last standard therapy. Pts were randomized 2:1 to receive best supportive care plus either REG (160 mg od po, 3 wks on/1 wk off) or placebo (PL). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate, disease control rate, safety and quality of life (QoL). Efficacy analyses across prespecified subgroups were evaluated using univariate Cox regression. Results: 760 pts were randomized (REG: 505; PL: 255). The OS primary endpoint was met at a preplanned interim analysis. OS and PFS were significantly improved in REG arm compared to PL arm: hazard ratio (HR) for OS 0.77 (95% CI 0.64-0.94, 1-sided p=0.0052), median OS 6.4 vs 5.0 mos; HR for PFS 0.49 (95% CI 0.42-0.58, 1-sided p<0.000001), median PFS 1.9 vs 1.7 mos. Comparable OS and PFS benefits were observed in exploratory subgroup analyses by region, age, time from diagnosis of mCRC to randomization, prior lines of treatment, and KRAS status (shown in table). The most common grade 3+ AEs related to REG were hand-foot skin reaction (16.6%), fatigue (9.6%), hypertension (7.2%), diarrhea (7.2%) and rash/desquamation (5.8%). QoL data will be presented. Conclusions: REG demonstrated statistically significant improvement in OS and PFS over PL, as well as comparable efficacy benefits across pt subgroups analyzed. [Table: see text]

We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.

LBA65 The Canadian Cancer Trials Group PA.7 trial: Results of a randomized phase II study of gemcitabine (GEM) and nab-paclitaxel (Nab-P) vs GEM, nab-P, durvalumab (D) and tremelimumab (T) as first line therapy in metastatic pancreatic ductal adenocarcinoma (mPDAC)

9003 Background: Toripalimab in combination with chemotherapy showed significant improvement over chemotherapy alone in progression-free survival (PFS) and overall survival (OS) as first-line treatment of advanced NSCLC at the final PFS analysis of the CHOICE-01 study (NCT03856411). Here we report the final OS analysis. Methods: Patients (n=465) with treatment-naïve, advanced NSCLC without EGFR/ALK mutations were randomized 2:1 to receive toripalimab 240 mg (n=309) or placebo (n=156) in combination with chemotherapy for 4-6 cycles, followed by maintenance toripalimab or placebo plus standard care until disease progression, intolerable toxicity, or completion of 2 years of treatment. Patients from the placebo arm were actively crossed-over to receive toripalimab upon disease progression. The primary endpoint was PFS. The secondary endpoints included OS and safety. Results: By the cutoff date of August 31, 2022, when 283 events triggered the final OS analysis, the median survival follow up was 19.4 months. A significant improvement in OS was observed for the toripalimab arm over the placebo arm: HR=0.73 (95% CI: 0.57-0.93), two-sided p=0.0108, median OS 23.8 vs 17.0 months. A consistent effect on OS, favoring the toripalimab arm, was observed all PD-L1 expression subgroups. The OS benefit is greater in non-squamous NSCLC, HR=0.50 (95% CI: 0.36-0.70), median OS 27.8 vs 15.9 months, whereas no significant difference was found in the squamous subgroup (mOS 19.6 vs 18.1 months) despite a significant PFS improvement. The squamous subgroup had a high 70% crossover rate. No new safety signal was identified since the interim report. The incidence of Grade ≥3 adverse events (AEs) (78.9% vs 82.1%) was similar between the two arms. AEs leading to discontinuation of toripalimab/placebo (14.3% vs 3.2%), fatal AEs (5.5% vs 2.6%), and immune-related (irAEs) (50.6% vs. 21.2%) were more frequent in the toripalimab arm. Whole exome sequencing results indicated patients with mutations in the FAK-PI3K-Akt pathway achieved significantly better OS from the toripalimab arm. Conclusions: The addition of toripalimab to chemotherapy in patients with advanced NSCLC provided significant OS benefit than chemotherapy alone with a manageable safety profile. These results support the use of toripalimab with chemotherapy as 1 st line therapy for advanced NSCLC patients without EGFR/ALK mutations. Clinical trial information: NCT03856411 .

Efficacy of brentuximab vedotin combination treatment in patients with relapsed or refractory diffuse large B-cell lymphoma with CD30 <1% expression

CANCERT he TROP2-targeting antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) significantly improved progression-free survival (PFS) and overall survival (OS) in comparison with pemetrexed plus platinum-based therapy in patients with EGFR-mutated non-small cell lung cancer (NSCLC) that had progressed after an EGFR tyrosine kinase inhibitor (TKI) according to the results of the OptiTROP-Lung04 trial. 1 These findings, which were presented at the 2025 European Society for Medical Oncology Congress by Li Zhang, MD, an oncologist at the Guangdong Provincial Clinical Research Center for Cancer in Guangzhou, China, and were published simultaneously in The New England Journal of Medicine, confirmed the findings from an earlier phase 2 trial of sac-TMT, which showed significant improvements in PFS and OS in comparison with docetaxel. 2 The phase 3 trial enrolled 376 patients with EGFR-mutated locally advanced or metastatic nonsquamous NSCLC that had progressed after a prior EGFR TKI (94.7% of the patients had received a third-generation EGFR TKI).Patients were randomly assigned to sac-TMT or pemetrexed plus platinum-based chemotherapy.The trial enrolled only Asian patients.The final PFS analysis showed a 4-month improvement in median PFS with sac-TMT in comparison with chemotherapy (8.3 vs. 4.3 months; hazard ratio [HR], 0.49; 95% CI, 0.39-0.62).A preplanned interim OS analysis that was conducted at a median follow-up of 18.9 months showed a 40% reduction in the risk for death with sac-TMT versus chemotherapy (HR, 0.60; 95% CI, 0.44-0.82;two-sided p = .001).The median OS was not reached for patients on sac-TMT but was 17.4 months for patients on chemotherapy.The OS rate at 18 months was 65.8% for patients on sac-TMT and 48.0% for patients on chemotherapy.The majority of the patients who discontinued the trial went on to have subsequent anticancer treatment.Approximately half of the patients in the sac-TMT arm (41.9%) and the chemotherapy arm (53.6%) had subsequent chemotherapy.Subsequent ADCs were given to 1.4% of the patients assigned to sac-TMT and to 19.6% of the patients assigned to chemotherapy.The rates of grade 3 or higher treatment-related adverse events were similar for sac-TMT (58.0%) and chemotherapy

Two randomized trials in the cytokine era showed that cytoreductive nephrectomy (CN) had a role in metastatic renal cell carcinoma (mRCC), increasing life expectancy. The survival benefit of tyrosine kinase inhibitors (TKIs), including first-line sunitinib and pazopanib, in mRCC has been demonstrated, but the majority of patients enrolled in the pivotal phase III studies had undergone nephrectomy. Therefore it is unknown if similar survival benefit with targeted agents could be achieved without CN. We hypothesize that in these patients CN could increase overall survival (OS) in comparison to targeted therapy without CN. We also will investigate mechanisms of primary and secondary resistance to TKIs in patients with mRCC and identify prognostic or predictive biomarkers. This is a randomized, open-label, controlled, multicenter phase 3 study comparing sunitinib or pazopanib vs CN followed by sunitinib or pazopanib as first-line therapy for patients with mRCC who have not received surgery and prior systemic treatment for metastatic disease. We will identify 270 patients eligible for randomization. The planned treatment duration per patient will be until progressive disease is observed. Secondary endpoints are the evaluation of progression-free survival (PFS) and response rate and the assessment of the safety profile. Exploratory objectives include the evaluation of circulating tumor cells and circulating tumor DNA and correlation with response/resistance to treatment. The study is enrolling patients. The use of CN in addition to targeted therapy in patients with renal cell carcinoma with synchronous metastases could lead to a significant improvement in OS and PFS.

5001 Background: Tak is an oral selective nonsteroidal 17, 20-lyase inhibitor that blocks the synthesis of gonadal and adrenal androgens. We evaluated the clinical benefit of Tak with ADT in pts with newly diagnosed mHSPC. Methods: Pts with mHSPC with a Zubrod performance status (PS) of 0-2 and a PSA of ≥ 2 ng/ml were randomized 1:1 to ADT+Tak (300 mg twice daily) or ADT+Bic (50 mg daily). Stratification factors included PS (0-1 vs ≥2), extent of disease (minimal vs extensive), and receipt of ADT prior to registration (yes vs no). The primary endpoint was overall survival (OS). Secondary endpoints were progression free survival (PFS; based on PSA, imaging or clinical progression), PSA at 7 months (≤0.2 vs 0.2 < PSA; ≤-4 vs. > 4 ng/ml) and adverse event (AE) profile. With 2.75 yrs to accrue 1,186 eligible pts and 3 additional yrs of follow-up, we would have 90% power to determine a 33% improvement in OS from 54 to 72 mos (1-sided α = 0.025). A final analysis was pre-specified after 523 deaths using a 1-sided α = 0.022 to account for interim analyses. Results: Between 3/2013 and 7/2017, 1,313 pts were randomized and 1,279 were included in the intention-to-treat (ITT) analysis (32 pts were ineligible and 2 pts withdrew consent). Median age was 68 yrs and 10% of subjects were Black. Median PSA was 30 ng/mL (range 2-6710) and 49% of pts had extensive disease. After a median follow-up of 4.9 yrs, PFS and PSA response were significantly improved with Tak over Bic but no significant improvement in OS was observed (Table). More grade 3/4 AEs occurred in Tak vs. Bic arms (43% vs. 14%), and included hypertension (20% vs. 5%) and fatigue (5% vs. 2%). Five pts in Tak and 1 pt in the Bic arm had grade 5 AE. Conclusions: Despite clinically meaningful improvement in various outcome measures with Tak+ADT over Bic+ADT in this representative population of mHSPC, the improvement in OS did not meet the pre-specified criteria for statistical significance. The median OS of 70 mos in the control arm (standard ADT) was higher than that reported in contemporary phase 3 trials in this setting, and 16 mos higher than originally estimated. This trial sets a new landmark for survival estimates when pts with mHSPC have access to multiple approved subsequent life-prolonging therapies. Funding: NIH/NCI/NCTN grants U10CA180888, U10CA180819, U10CA180820; U10CA180821; and in part by Millennium Pharmaceuticals, Inc. (Takeda Pharmaceutical Company LTD) Clinical trial information: NCT01809691. [Table: see text]

Immune checkpoint inhibitor (ICI) monotherapy and chemotherapy (CT) have been used to treat recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC), with demonstrated survival benefits and good safety. However, whether combination therapy is superior to CT alone remains unclear. We summarized the existing evidence comparing the effectiveness and toxicities of ICI combined with CT versus CT alone. Online databases was conducted for eligible randomized controlled trials (RCTs) published up to November 1, 2023. Progression-free survival (PFS) and overall survival (OS) were the primary endpoint. Objective response rates (ORRs) and adverse events (AEs) were the secondary endpoint. Three randomized controlled trials (Capture-1st, JUPITER-02, and RATIONALE-309) were included. First-line ICI therapy combined with CT showed significant improvement in PFS (hazard ratio[HR], 0.53; 95% confidence interval[CI]: 0.44-0.64), OS (HR, 0.63;95%CI: 0.49-0.81) and ORRs (odds ratio[OR], 1.79;95%CI: 1.30-2.46), when compared with CT alone. AEs ≥ grade 3 during treatment and treatment-related deaths were not significantly different between the two groups. In patients with R/M-NPC, ICI therapy combined with CT showed improved ORRs, PFS, and OS, with similar safety as CT alone.

Efficacy and safety of first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) combined with chemotherapy or antiangiogenic therapy as first-line treatment in patients with EGFR-mutant non-small cell lung cancer: A systematic review and meta-analysis.

Lenalidomide Compared to Ixazomib Maintenance in Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

En bloc spondylectomy is the gold standard for surgical resection of sacral chordomas (CHO), but the effect of extent of resection on recurrence and survival in patients with CHO of the cervical spine remains elusive. MEDLINE, Embase, Scopus, and Cochrane were systematically reviewed. Patients with cervical CHO treated at three tertiary-care academic institutions were reviewed for inclusion. We performed an individual participant data meta-analysis to assess the overall survival (OS) and progression free survival (PFS) after en bloc-gross total resection (GTR) and intralesional-GTR compared to subtotal resection (STR). We then performed an intention-to-treat analysis including all patients with attempted en bloc resection in the en bloc group, regardless of the surgical margins. There was a total of 13 series including 161 patients with cervical CHO, including our current series of 22 patients. GTR (en bloc-GTR + intralesional-GTR) was associated with a significant decrease in the risk of local progression (pooled hazard ratio (PHR) = 0.22; 95% CI 0.08-0.59; p = 0.003) and risk of death (PHR 0.31; 95%; CI 0.12-0.83; p = 0.020). A meta-regression analyses determined that intralesional-GTR improved PFS (PHR 0.35; 95% CI 0.16-0.76; p = 0.009) as well as OS (PHR 0.25; 95% CI 0.08-0.79; p = 0.019) when compared to STR. En bloc-GTR was associated with a significant reduction in the risk of local progression (PHR 0.06; 95% CI 0.01-0.77; p = 0.030), but not a decreased OS (PHR 0.50; 95% CI 0.19-1.27; p = 0.145). Our intention-to-treat analyses revealed a near significant improvement in OS for the en bloc group (PHR: 0.15; 95% CI 0.02-1.22; p = 0.054), and nearly identical improvement in PFS. Radiation data was not available for the studies included in the meta-analysis. This is the first and only meta-analysis of patients with cervical CHO. We found that both en bloc-GTR and intralesional-GTR resulted in improved local tumor control when compared to STR.

The role of sidedness in second-line therapy for RAS wild-type colorectal cancer: a network meta-analysis (NMA)

BACKGROUND AND OBJECTIVEUterine papillary serous cancer (UPSC) represents only 10% of all uterine cancers and is associated with a significantly worse prognosis compared with other histological types of endometrial cancers. It closely resembles the behavior of ovarian carcinoma.DESIGN AND SETTINGRetrospective study in a referral center covering period from February 1989 to January 2009.PATIENTS AND METHODSEighteen patients who underwent definitive surgery followed by adjuvant therapy—platinum-based chemotherapy, radiotherapy, or both—were reviewed. Median age was 62 years (range, 52–76 years). All patients underwent total abdominal hysterectomy and salpingo-oophorectomy. Positive lymph nodes were found in 4 of 7 patients who underwent lymph node sampling/dissection. Seven patients had stage I/II disease, whereas 11 patients had stage III disease. Six patients received chemotherapy, 5 patients received radiation therapy, while 7 patients received both chemotherapy and radiation therapy.RESULTMedian follow-up was 27 months. The median survival and relapse-free survival were 33 and 23 months, respectively. Eight patients were alive and free of disease, of whom 5 patients were stage I/II and 4 patients were stage III. Distant metastasis was the most common site of relapse. Early stage (I/II) was associated with significant improvement in relapse-free survival (RFS) and overall survival (OS) (P=.004 and P=.05, respectively). The combined-modality treatment including chemotherapy-radiotherapy showed statistically significant improvement in RFS (P=.012), while the improvement in OS did not reach statistical significance (P=.12).CONCLUSIONThis study indicates that postoperative combined treatment with chemotherapy and radiation therapy plays a role in the management of UPSC by improving RFS. Distant metastasis remains the major site of relapse. Future studies using combined-modality therapy are needed to improve the outcome in patients with UPSC.