Cycles Of Platinum-based Chemotherapy Research Articles

Surufatinib plus PD-1/L1 inhibitors as maintenance therapy following first line (1L) platinum-based chemotherapy combined with PD-1/L1 inhibitors in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC).

e15109 Background: Pts with ES-SCLC have a poor prognosis. PD-1/L1 inhibitors combined with chemotherapy as 1L treatment has been demonstrated to improve the survival. Yet, pts are prone to progression after chemo-immunotherapy followed by anti-PD-1/L1 monotherapy. A multicenter, single-arm phase II study was conducted to evaluate the efficacy and safety of surufatinib (a small-molecule inhibitor of VEGFR 1-3, FGFR1 and CSF-1R) combined with PD-1/L1 inhibitors in pts with ES-SCLC as 1L maintenance therapy. Methods: Key inclusion criteria were cytologically or pathologically confirmed ES-SCLC, ECOG PS 0-1, no disease progression after 4-6 cycles platinum-based chemotherapy combined with PD-1/L1 inhibitors. Enrolled pts received surufatinib (250mg, po, QD) plus PD-1/L1 inhibitors (same as that in prior 1L therapy: Durvalumab, Sintilimab, Toripalimab or Serplulimab) until disease progression or intolerable toxicity. The primary endpoint is progression free survival (PFS) per RECIST 1.1 by investigator. Results: From Sept 2022 to July 2023, 21 pts were enrolled. The median age was 62 years. 90.5% were male, 85.7% were former and current smokers and 52.4% had ECOG PS of 0, 11 pts completed 6 cycles of platinum-based chemotherapy combined with PD-1/L1 inhibitors, and 12 pts received durvalumab in 1L therapy. As of 20 Nov, 2023, the median follow-up duration was 9.2 months. Objective response rate (ORR) was 14.3% and DCR (disease control rate) was 71.4%. The mPFS of 1L maintenance therapy was 4.0 months (95%CI: 2.0-5.6). The mPFS from 1L treatment to disease progression was 8.7 months. mOS was not reached, with 3 mo- , 6 mo- and 9 mo- OS rate was 100%, 94.4% and 75.6%, respectively. 21 (100%) pts experienced treatment-emergent adverse events (TEAEs), and 8 (38.1%) pts experienced grade ≥3 TEAEs, most commonly with platelet count decreased, neutrophil count decreased and pneumonia. There was no treatment-related death. Conclusions: Surufatinib combined with PD-1/L1 inhibitors showed encouraging efficacy and tolerable safety profile as 1L maintenance therapy. Further OS follow-up is warranted. Clinical trial information: NCT05509699 .

Association of CCND1 rs9344 polymorphism with lung cancer susceptibility and clinical outcomes: a case-control study.

Cyclin D1 (CCND1) plays a pivotal role in cancer susceptibility and the platinum-based chemotherapy response. This study aims to assess the relationship between a common polymorphism (rs9344 G > A) in CCND1 gene with cancer susceptibility, platinum-based chemotherapy response, toxicities and prognosis of patients with lung cancer. This study involved 498 lung cancer patients and 213 healthy controls. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Unconditional logistical regression analysis and meta-analysis were performed to evaluate the associations. The lung adenocarcinoma risk was significantly higher in patients with AA than GG + GA genotype (adjusted OR = 1.755, 95%CI = 1.057-2.912, P = 0.030). CCND1 rs9344 was significantly correlated with platinum-based therapy response in patients receiving PP regimen (additive model: adjusted OR = 1.926, 95%CI = 1.029-3.605, P = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428-90.100, P = 0.022) and in the ADC subgroups (recessive model: adjusted OR = 3.345, 95%CI = 1.276-8.765, P = 0.014). Furthermore, an increased risk of overall toxicity was found in NSCLC patients (additive model: adjusted OR = 1.395, 95%CI = 1.025-1.897, P = 0.034; recessive model: adjusted OR = 1.852, 95%CI = 1.088-3.152, P = 0.023), especially ADC subgroups (additive model: adjusted OR = 1.547, 95%CI = 1.015-2.359, P = 0.043; recessive model: adjusted OR = 2.030, 95%CI = 1.017-4.052, P = 0.045). Additionally, CCND1 rs9344 was associated with an increased risk of gastrointestinal toxicity in non-smokers (recessive model: adjusted OR = 2.620, 95%CI = 1.083-6.336, P = 0.035). Non-significant differences were observed in the 5-year overall survival rate between CCND1 rs9344 genotypes. A meta-analysis of 5432 cases and 6452 control samples did not find a significant association between lung cancer risk and CCND1 rs9344 polymorphism. This study suggests that in the Chinese population, CCND1 rs9344 could potentially serve as a candidate biomarker for cancer susceptibility and treatment outcomes in specific subgroups of patients.

The Role of Serum IL-23 and Volatile Organic Compound Levels to RECIST 1.1 in The Evaluation of Therapeutic Response in Lung Cancer

The Response Evaluation Criteria in Solid Tumors (RECIST 1.1) is the gold standard for the assessment of lung cancer progression. However, the assessment and diagnosis of early treatment failure is challenging due to the limitations of current tools, as well as the long intervals and unavoidable side effects.This study aims to correlate volatile organic compound (VOC) patterns, serum level of interleukin-23 (IL-23), and RECIST 1.1 to assess chemotherapy response in lung cancer patients at Saiful Anwar Hospital. A prospective observational study was performed to 47 lung cancer patients who received three cycles of platinum-based chemotherapy. Using the Breath Analyzer to measure certain volatile organic compounds (VOCs), the study observed that three of the seven VOCs examined, formaldehyde (CH2O), toluene (C7H8), and hexane (C6H14), showed lower levels after three cycles of chemotherapy. Furthermore, there was a negative correlation between RECIST1.1 and acetone (C3H6O) (p=0.023), while RECIST1.1 and methane (CH4) had a positive correlation (p=0.011). Moreover, a significant positive correlation was observed between IL-23 after-chemotherapy and RECIST 1.1 (p=0.000). According to this study, a correlation exists between methane, IL-23, and RECIST 1.1 after three cycles of chemotherapy. The increase in methane and IL-23 aligns with the disease progression determined by RECIST 1.1. Furthermore, The decrease in acetone after chemotherapy showed a negative correlation with RECIST1.1, consistent with disease progression.Keywords: Volatile Organic Compound, Interleukin-23, RECIST 1.1.

Intraoperative implantation of 125I seeds improves prognosis in refractory stage IIIB cervical cancer: a case report and literature review

BackgroundConcurrent chemoradiation is the standard treatment for advanced cervical cancer. However some patients still have a poor prognosis, and currently, there is no effective treatment for recurrence. In recent years, 125I seed implantation therapy has emerged as a treatment for advanced malignant tumors including surgically unresectable tumors, residual tumors after surgical resection, and metastatic tumors. However, the use of 125I seeds implantation in primary advanced cervical cancer has not been reported. In this study, we present a case of stage IIIB cervical cancer in a patient who had poor response to radiotherapy and chemotherapy. Subsequently, a radical hysterectomy was performed, and 125I radioactive seeds were successfully implanted during the surgery. This effectively controlled the lesions that were resistant to radiotherapy and had the potential to improve the prognosis.Case presentationA 56-year-old woman was diagnosed with stage IIIB (FIGO 2009) IIIC1r (FIGO 2018) squamous carcinoma of the cervix. After receiving 4 cycles of platinum-based chemotherapy and 30 rounds of radiotherapy, she underwent a radical hysterectomy. The localized cervical lesions were reduced, but there was no reduction in the size of the enlarged pelvic lymph nodes. Therefore, 125I seed implantation was performed under direct surgical vision for the right paracervical lesion and the enlarged pelvic lymph nodes on the right side. During the 18-month follow-up period, the enlarged lymph nodes subsided without any signs of recurrence or metastasis.ConclusionIntraoperative implantation of 125I seeds in lesions that are difficult to control with radiotherapy or in sites at high risk of recurrence is a feasible and effective treatment option for patients with advanced squamous cervical cancer, and it may contribute to improved survival.

Real world outcomes for maintenance avelumab treatment in locally advanced/metastatic urothelial cancer after platinum-based chemotherapy.

584 Background: Maintenance Avelumab after platinum-based chemotherapy in metastatic-/locally advanced urothelial carcinoma has shown overall and progression free survival benefit in the JAVELIN Bladder 100 trial. We analysed real world outcomes from 6 UK centres. Methods: Retrospective electronic patient records review was carried out for patients treated between January 2021 and September 2023 at 6 UK centres. Patients whose disease had not progressed after platinum-based chemotherapy were started on maintenance avelumab 800mg given at 2 weekly intervals, starting within 12 weeks of last day of chemotherapy as per the National Cancer Drug Fund criteria. Survival outcomes were established using the Kaplan Meier method and compared by a log rank test using SPSS. Results: In total 80 patients (median age 73 years-range 21-86) were included of which 68% were male and 32% were female. 31(38.8%) had prior upper tract and 49(61.2%) had bladder cancers. Metastases were in the nodes only in 33(41.5%) patients whilst 16.9% and 42.3% had bone and visceral metastases respectively. The number of patients with ECOG PS 0,1 and 2 were 36 (45.0%), 33 (41.3%), and 10 (12.5%), respectively. After a median of six cycles of platinum-based chemotherapy, 11.3% had a complete response, and 54.9% had a partial response. Patients then proceeded to maintenance avelumab treatment. Before treatment, the median Neutrophil to Lymphocyte Ratio (NLR) was 2.89. The number of patients with NLR ≤2.89 was 37 (46.3%), and with >2.89 were 38 (47.9%). Median number of cycles were 9 (range 1-66). At a median follow-up of 16.7 months, the median PFS was 8.3 months (95% CI 4.8-15.4). At the data cut-off, 37 patients had died, and 40 patients had progressed. Any grade of adverse event occurred in 34 (42.5%) patients. Grade 3 or higher toxicity rate was 7.5%. Two grade 3 allergic reactions were seen. One patient had Grade 3 immune mediated hepatitis and one patient had grade 3 immune mediated arthritis. Two grade 2 immune mediated colitis were reported. The ORR of avelumab maintenance therapy was 12.5%. 2 patients had a complete response, 8 had a partial response, and 43(53.7%) had stable disease. Within the limit of our small data set, univariate analysis for PFS revealed that there was no significant association between PFS and visceral metastases (p=0.2), bone metastases (p=0.2), node only metastases (p=0.6), primary site(p=0.9), and ECOG PS (p=0.6). However, NLR was a significant prognostic factor for PFS. The median PFS in patients with NLR ≤2.89 vs >2.89 was 16.9 vs 4.2 months, respectively (p=0.001). Conclusions: Our multi centre UK real world data confirms that maintenance Avelumab treatment is well tolerated, and its efficacy data is consistent with previously reported clinical studies.

Impact of the response to platinum-based chemotherapy on the second-line immune checkpoint inhibitor monotherapy in non-small cell lung cancer with PD-L1 expression ≤49%: a multicenter retrospective study.

The efficacy of second-line immune checkpoint inhibitor (ICI) therapy is limited in non-small cell lung cancer (NSCLC) patients with ≤ 49% PD-L1 expression. Although chemoimmunotherapy is a promising strategy, platinum-based chemotherapy followed by ICI monotherapy is often used to avoid synergistic adverse events. However, predictors of the efficacy of ICI monotherapy after platinum-based chemotherapy in NSCLC with ≤ 49% PD-L1 expression remain scarce. This multicenter retrospective study evaluated 54 advanced or recurrent NSCLC patients with ≤ 49% PD-L1 expression who were treated with second-line ICI monotherapy following disease progression on first-line platinum-based chemotherapy at nine hospitals in Japan. The impact of response to platinum-based chemotherapy on the efficacy of subsequent ICI monotherapy was investigated. The response to first-line platinum-based chemotherapy was divided into two groups: the non-progressive disease (PD) group, which included patients who did not experience disease progression after four cycles of chemotherapy, and the PD group, which included patients who showed initial PD or could not maintain disease control during the four cycles of chemotherapy and switched to second-line ICI monotherapy. Among the 54 patients, 32 and 22 were classified into the non-PD and PD groups, respectively. The non-PD group showed better response rates (p = 0.038) and longer overall survival (OS) with ICI monotherapy (p = 0.023) than the PD group. Multivariate analysis identified that maintaining a non-PD status after four cycles of chemotherapy was an independent prognostic factor for ICI monotherapy (p = 0.046). Moreover, patients with a modified Glasgow Prognostic Score (mGPS) of 0 showed a tendency for longer OS with ICI monotherapy (p = 0.079), and there was a significant correlation between maintaining non-PD after four cycles of chemotherapy and an mGPS of 0 (p = 0.045). Maintaining a non-PD status after four cycles of platinum-based chemotherapy was a predictor of OS after second-line ICI monotherapy. These findings will help physicians select the most suitable treatment option for NSCLC patients who were treated with platinum-based chemotherapy and switched to second-line treatment. Those who experienced early PD during platinum-based chemotherapy should not be treated with ICI monotherapy in the second-line setting.

A Real-World Retrospective Analysis of the Management of Advanced Urothelial Carcinoma in Canada.

Locally advanced or metastatic urothelial carcinoma (aUC) presents a significant challenge with high mortality rates. Platinum-based chemotherapy remains the established frontline standard of care, and a switch-maintenance strategy with immunotherapy has now emerged as a new standard for aUC patients without disease progression, following initial platinum therapy. Examining the treatment patterns is imperative, given the evolving therapeutic landscape. In this study, we conducted a retrospective medical chart review of 17 Canadian oncologists treating patients with aUC to assess unmet needs in Canadian aUC patient care. Data from 146 patient charts were analyzed, revealing important clinical insights about the management of aUC. A substantial proportion of patients (53%) presented with de novo metastatic disease, which was possibly influenced by pandemic-related care disruptions. Variability was evident in the cisplatin eligibility criteria, with a majority (70%) of oncologists utilizing a 50 mL/min threshold. Most favored four cycles of platinum-based chemotherapy to spare the bone marrow for future therapies and prevent patient fatigue. Notably, some eligible patients were kept under surveillance rather than receiving maintenance therapy, suggesting a potential gap in awareness regarding evidence-based recommendations. Furthermore, managing treatment-related adverse events was found to be one of the biggest challenges in relation to maintenance immunotherapy. In conclusion, our findings provide the first comprehensive overview of aUC treatment patterns in Canada following the approval of maintenance immunotherapy, offering insights into the decision-making process and underscoring the importance of evidence-based guidelines in aUC patient management.

Long-term cardiotoxicity in germ cell cancer survivors after platinum-based chemotherapy: cardiac MR shows impaired systolic function and tissue alterations

ObjectivesLong-term toxicities of germ cell cancer (GCC) treatment are of particular importance in young men with a life expectancy of several decades after curative treatment. This study aimed to investigate the long-term effects of platinum-based chemotherapy on cardiac function and myocardial tissue in GCC survivors by cardiac magnetic resonance (CMR) imaging.MethodsAsymptomatic GCC survivors ≥ 3 years after platinum-based chemotherapy and age-matched healthy controls underwent CMR assessment, including left ventricular (LV) and right ventricular (RV) ejection fraction (EF), strain analysis, late gadolinium enhancement (LGE) imaging, and T1/T2 mapping.ResultsForty-four survivors (age 44 [interquartile range, IQR 37–52] years; follow-up time 10 [IQR 5–15] years after chemotherapy) and 21 controls were evaluated. LV- and RVEF were lower in GCC survivors compared to controls (LVEF 56 ± 5% vs. 59 ± 5%, p = 0.017; RVEF 50 ± 7% vs. 55 ± 7%, p = 0.008). Seven percent (3/44) of survivors showed reduced LVEF (< 50%), and 41% (18/44) showed borderline LVEF (50–54%). The strain analysis revealed significantly reduced deformation compared to controls (LV global longitudinal strain [GLS] -13 ± 2% vs. -15 ± 1%, p < 0.001; RV GLS -15 ± 4% vs. -19 ± 4%, p = 0.005). Tissue characterization revealed focal myocardial fibrosis in 9 survivors (20%) and lower myocardial native T1 times in survivors compared to controls (1202 ± 25 ms vs. 1226 ± 37 ms, p = 0.016). Attenuated LVEF was observed after two cycles of platinum-based chemotherapy (54 ± 5% vs. 62 ± 5%, p < 0.001).ConclusionBased on CMR evaluation, combination chemotherapy with cumulative cisplatin ≥ 200 mg/m2 is associated with attenuated biventricular systolic function and myocardial tissue alterations in asymptomatic long-term GCC survivors.Clinical relevance statementPlatinum-based chemotherapy is associated with decreased systolic function, non-ischemic focal myocardial scar, and decreased T1 times in asymptomatic long-term germ cell cancer survivors. Clinicians should be particularly aware of the risk of cardiac toxicity after platinum-based chemotherapy.Key Points• Platinum-based chemotherapy is associated with attenuation of biventricular systolic function, lower myocardial T1 relaxation times, and non-ischemic late gadolinium enhancement.• Decreased systolic function and non-ischemic late gadolinium enhancement are associated with a cumulative cisplatin dose of ≥ 200 mg/m2.• Cardiac MRI can help to identify chemotherapy-associated changes in cardiac function and tissue in asymptomatic long-term germ cell cancer survivors.Graphical

P217 - FOur Cycles of platinum-based chemotherapy in advanced or metastatic Urothelial carcinoma Compared to Six Cycles: A retrospective cohort study (FOCUS, KCSG-GU23-08)

P217 - FOur Cycles of platinum-based chemotherapy in advanced or metastatic Urothelial carcinoma Compared to Six Cycles: A retrospective cohort study (FOCUS, KCSG-GU23-08)

Residual ctDNA Detection Predicts Benefit From Definitive Chemoradiotherapy and Immune Checkpoint Inhibitors in Locally Advanced NSCLC

Therapeutic efficacy differs across unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients receiving definitive chemoradiotherapy (CRT), and the dynamic change in circulating tumor DNA (ctDNA) is closely associated with clinical outcomes. However, evidence for the predictive effect of ctDNA in LA-NSCLC patients with CRT and immunotherapy, the current standard of care, remains limited. It is unclear whether residual ctDNA after definitive CRT can guide clinical decisions on further use of immune checkpoint inhibitors (ICIs) consolidation. We prospectively included 73 patients with unresectable stage II-III NSCLC. All patients received definitive concurrent or sequential CRT, with the prescribed dose of 60 Gy and ≥2 cycles of platinum-based chemotherapy. Thirty-seven (50.7%) patients further underwent ICIs therapy (18 durvalumab, 9 pembrolizumab, 10 others). Peripheral blood samples were collected from all patients before any treatment (baseline), 1 month after CRT (post-CRT), and at the time of progression. All plasma specimens were analyzed with next-generation sequencing panel of 474 cancer-related genes. Plasma samples with ≥1 variant detected were defined as detectable ctDNA. The primary endpoint was progression-free survival (PFS). After the median follow-up of 25.4 months, median overall survival (OS) was not reached (NR), and median PFS was 16.7 months (95% CI, 12.4-26.6) for all patients. Compared with baseline, ctDNA abundance significantly decreased after definitive CRT (P<0.001) but relatively increased at progression (P = 0.051). Patients treated with CRT plus ICIs exhibited significantly longer OS (median, NR vs 22.1 months [95% CI, 16.7-NR]; P = 0.002) and PFS (median, 24.8 months [95% CI, 16.1-NR] vs 11.4 months [95% CI, 6.5-NR]; P = 0.016) than those with CRT alone. Post-CRT residual ctDNA was associated with significantly poorer OS (median, 18.3 months [95% CI, 14.8-NR] vs NR; P = 0.002) and PFS (median, 6.5 months [95% CI, 5.6-NR] vs 24.8 months [95% CI, 18.8-NR]; P<0.001), whereas baseline ctDNA predicted neither OS (P = 0.310) nor PFS (P = 0.570). For patients with post-CRT detectable ctDNA, further ICIs therapy brought significant benefit in both OS (median, NR vs 14.8 months [95% CI, 12.0-NR]; P = 0.012) and PFS (median, 16.1 months [95% CI, 5.8-NR] vs 6.2 months [95% CI, 4.2-NR]; P = 0.043). However, in patients with post-CRT ctDNA clearance, there was no significant difference in OS (P = 0.080) or PFS (P = 0.151) between patient with and without ICIs, which suggested less clinical benefit. Post-CRT residual ctDNA predicted worse survival in LA-NSCLC, but indicated more benefit from further ICIs therapy and thereby could facilitate personalization of consolidation immunotherapy. Further prospected studies with large sample size are warranted to validated these findings.

Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Analysis from JAVELIN Bladder 100 by Duration of First-line Chemotherapy and Interval Before Maintenance

BackgroundIn the JAVELIN Bladder 100 phase 3 trial, avelumab first-line maintenance + best supportive care (BSC) prolonged overall survival (OS) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (advanced UC) without progression after first-line platinum-based chemotherapy. ObjectiveTo report post hoc analyses of subgroups defined by the duration of first-line chemotherapy and interval before maintenance. Design, setting, and participantsPatients with advanced UC without progression after four to six cycles of platinum-based chemotherapy and a 4–10-wk interval after chemotherapy (n = 700) were randomized to receive avelumab + BSC or BSC alone. Subgroups were defined by duration (quartile [Q]) and estimated number of cycles of chemotherapy, and interval between chemotherapy and maintenance. The median follow-up was >19 mo in both arms. Outcome measurements and statistical analysisOS (primary endpoint), PFS, and safety were assessed. Results and limitationsHazard ratios (95% confidence interval) for OS with avelumab + BSC versus BSC alone were as follows: by chemotherapy duration—<Q1: 0.65 (0.42–1.02), Q1–Q2: 0.79 (0.50–1.27), Q2–Q3: 0.74 (0.50–1.10), and >Q3: 0.63 (0.39–1.00); by number of cycles—four cycles: 0.69 (0.48–1.00), five cycles: 0.98 (0.57–1.71), and six cycles: 0.66 (0.47–0.92); and by interval—4–<6 wk: 0.75 (0.54–1.04), 6–<8 wk: 0.67 (0.43–1.06), and 8–10 wk: 0.69 (0.47–1.02). Results were similar for PFS. Safety was similar across subgroups. All analyses were exploratory. ConclusionsPost hoc analyses of OS and PFS in subgroups defined by first-line chemotherapy duration and interval before maintenance were generally consistent with the results in the overall population, with similar safety findings. Prospective trials are warranted to confirm these findings. Patient summaryAvelumab maintenance treatment helped patients with advanced urothelial cancer without disease progression after at least four cycles of prior chemotherapy, and who started maintenance treatment at least 4 wk after chemotherapy, to live longer.

Evaluating Real-World Characteristics of Patients With Advanced Urothelial Carcinoma Eligible for Avelumab Maintenance Therapy: A Multicountry Retrospective Medical Chart Review.

Urothelial carcinoma (UC) is a malignancy of the urothelium that encompasses the renal pelvis, bladder, and urethra. Current treatment guidelines for advanced (ie, locally advanced or metastatic) UC recommend using avelumab maintenance therapy in patients with nonprogressive disease following first-line platinum-based chemotherapy. This study aimed to assess the representativeness of the patient population in the JAVELIN Bladder 100 (JB-100) trial, which examined the efficacy and safety of avelumab first-line maintenance, vs. real-world patients with advanced UC that had not progressed with first-line platinum-based chemotherapy treated between 2015 and 2018 by reviewing demographic and clinical characteristics. A medical chart review (MCR) study collected demographics and treatment characteristics for patients with advanced UC in the United States, the United Kingdom, and France. Data were analyzed descriptively for review with data collected from patients enrolled in JB-100. Clinical characteristics were consistent between JB-100 and the MCR. Most patients were male, received 4 to 6 cycles of platinum-based chemotherapy, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients in the MCR had either stable disease or a response with platinum-based chemotherapy (∼75% achieved a complete or partial response). Fewer than half (42.5%) of all patients in the MCR received subsequent therapy. Patient demographics, clinical characteristics, and treatment patterns from a MCR of patients with advanced UC that had not progressed following first-line platinum-based chemotherapy appeared similar to data from patients enrolled in JB-100. Future studies should examine whether real-world outcomes are consistent with findings from JB-100. NCT02603432.

The CHASIT study: sequential chemo-immunotherapy in patients with locally advanced urothelial cancer – a non-randomized phase II clinical trial

BackgroundPatients with locally advanced irresectable or clinically node positive urothelial cancer (UC) have a poor outcome. Currently, these patients can only be cured by receiving induction chemotherapy and, if an adequate radiological response is obtained, radical surgical resection. Long-term survival, however, strongly depends on the absence of residual tumor in the surgical resection specimen, i.e. a pathological complete response (pCR). The reported pCR rate following induction chemotherapy in locally advanced or clinically node-positive UC is 15%. The 5-year overall survival rate for patients achieving a pCR is 70–80% versus 20% for patients who have residual disease or nodal metastases. This clearly demonstrates the unmet need to improve clinical outcome of these patients. Recently, the JAVELIN Bladder 100 study demonstrated an overall survival benefit of sequential chemo-immunotherapy in patients with metastatic UC. The CHASIT study aims to translate these findings to the induction setting by assessing the efficacy and safety of sequential chemo-immunotherapy in patients with locally advanced or clinically node-positive UC. In addition, patient biomaterials are collected to investigate biological mechanisms of response and resistance to chemo-immunotherapy.MethodsThis multicenter, prospective phase II clinical trial includes patients with stage cT4NxM0 or cTxN1-N3M0 UC of the bladder, upper urinary tract or urethra. Patients who do not experience disease progression after 3 or 4 cycles of platinum-based chemotherapy are eligible for inclusion. Included patients receive 3 cycles of anti-PD-1 immunotherapy with avelumab followed by radical surgery. Primary endpoint is the pCR rate. It is hypothesized that sequential chemo-immunotherapy results in a pCR rate of ≥ 30%. To obtain a power of 80%, 64 patients are screened and 58 patients are included in the efficacy analysis. Secondary endpoints are toxicity, postoperative surgical complications, progression-free, cancer-specific and overall survival at 24 months.DiscussionThis is the first study to assess the potential benefit of sequential chemo-immunotherapy in patients with locally advanced or node positive UC. If the primary endpoint of the CHASIT study is met, i.e. a pCR rate of ≥ 30%, a randomized controlled trial is foreseen to compare this new treatment regimen to standard care.Trial registrationNCT05600127 at Clinicaltrials gov, registered on 31/10/2022.

EGFR tyrosine kinase inhibitors (TKIs) versus durvalumab (durva) following concurrent chemoradiation (CRT) in unresectable EGFR-mutant non-small-cell lung cancer (NSCLC).

8567 Background: Adjuvant osimertinib (osi) improves disease-free survival (DFS) in patients (pts) with resected, early-stage, EGFR-mutant (EGFRmut) NSCLC, yet the benefit of osi after CRT in pts with unresectable locally advanced NSCLC is unknown. Post-hoc analysis of the PACIFIC trial showed a lack of survival benefit with consolidation durva versus placebo in pts with EGFRmut NSCLC. Comparisons between consolidation durva and EGFR TKIs in unresectable EGFRmut NSCLC following CRT are lacking. Methods: We conducted a multi-institutional retrospective analysis of pts with stage III unresectable EGFRmut NSCLC (exon19 deletion, exon21 L858R), who received EGFR TKI or durva after ≥ 2 cycles of platinum-based chemotherapy plus definitive radiation therapy between 2015-2022. Baseline characteristics including age, sex, smoking history, PD-L1 status, and outcomes on DFS, overall survival (OS), and safety were collected. Multivariable (MVA) cox regression analysis was used for statistical analysis. Treatment-related adverse events (trAE) were defined using CTCAE 5.0. Results: Seventeen pts from 12 institutions received an EGFR TKI (osi, n=15; erlotinib, n=2), and 13 pts received consolidation durva. Median follow-up was 23 months. Median age of all pts was 61 years (IQR:52-72) and 76.7% were female. Most pts in both groups had never-smoked and had adenocarcinoma. All pts received ≥ 60 Gy of radiation with concurrent chemotherapy. PD-L1 expression was ≥ 50% in 1/10 (10%) pts treated with durva vs 6/13 (46.2%) treated with TKI, p=0.09. Median duration on treatment for EGFR TKI and durva was 12.2 months and 4.8 months, respectively. Pts treated with EGFR TKI had significantly longer 24-month DFS versus pts treated with durva after adjusting for stage (3A vs 3B vs 3C) (Table). Any grade tRAE occurred in 58.8% (10/17) of pts treated with EGFR TKI vs 38.5% (5/13) with durva. Grade &gt; 3 tRAE occurred in 15.4% (1 pneumonitis and 1 AST/ALT elevation) of pts treated with durva but in none of pts treated with EGFR TKI. Three pts within each arm came off treatment due to toxicity (EGFR TKI: 1 pneumonitis and 2 dermatitis; durva: 1 of each pneumonitis, Type 1 diabetes, AST/ALT elevation). Conclusions: EGFR TKI therapy after definitive CRT was associated with significantly longer DFS compared to durva in this retrospective study of pts with stage III unresectable EGFRmut NSCLC, without unanticipated safety signals. Follow-up is ongoing and OS outcomes will be evaluated subsequently. Further investigation is warranted to define the optimal therapy for locally advanced EGFRmut NSCLC. [Table: see text]

Long term disease-free survival in locoregional, metastatic and/or recurrent UCNT.

e18023 Background: Undifferentiated Carcinoma of Nasopharyngeal Type (UCNT) is a rare and aggressive type of head and neck cancer related to the Epstein Barr virus (EBV), genetic (HLA B5 in Algeria) and environmental factors. It is the most frequent histological variant of ENT cancers. It has geographically selective epidemiologic features unrelated to external carcinogens, and is known to be radiosensitive and chemosensitive. Methods: Seventy-one patients with biopsy-proven UCNT presenting to a single oncology unit between 2015 and 2022 were assessed for their long-term response to treatment. The sex ratio of cases was 3M: 1F; thirty-one patients (43%) were under the age of 50; 11 (15%) under the age of 35; and among these, there were two 19 year old males. The initial median World Health Organization (WHO) performance status was 1.6. These patients with locoregional (LR), recurrent (REC) and/or metastatic (MTS) UCNT were treated with monthly cycles of platinum-based chemotherapy of cisplatin (CDDP) 75 mg/m2 IV or Carboplatine AUC-4 and Docetaxel 75 mg/m2 IV followed by fluorouracil (5FU) 1000 mg/m2/day continuous IV infusion days 1 to 4 (TPF) in locally advanced disease, and with cisplatin (CDDP) 75 mg/m2 day 1 or Carboplatine AUC-5; and fluorouracil (5FU) 1000 mg/m2/d continuous IV infusion days 1 to 4 (PF) in recurrent and/or metastatic cases. The choice of systemic therapy was individualized based on patient characteristics including performance status, goals of therapy. Results: Those LR or MTS patients who were still alive without evidence of disease after 36+ months were categorized as complete responders (CRs). A subgroup of CRs was identified who had failed prior chemotherapy. MTS patients with less than three distant osseous sites underwent additional radiation therapy. Conclusions: Encouraging results for this particular type of head and neck cancer confirm the chemosensitivity of UCNT, and the observation of long-term responders makes curability a real consideration.

Impact of the number of cycles of platinum-based chemotherapy for early stage ovarian clear cell carcinoma on survival: a retrospective study

BackgroundOvarian clear cell carcinoma (OCCC) is a unique subtype of ovarian epithelial ovarian cancer. The number of chemotherapy cycles for early-stage patients is still debated. This study aimed to evaluate whether at least 4 cycles of adjuvant platinum-based chemotherapy have better prognostic value than 1–3 cycles in early-stage OCCC.MethodsWe retrospectively retrieved data from 102 patients with stage I-IIA OCCC between 2008 and 2017. All patients underwent complete surgical staging followed by adjuvant platinum-based chemotherapy. Kaplan-Meier curves and Multivariate Cox analysis were performed to estimate 5-year overall survival (OS) and progression-free (PFS) according to the number of chemotherapy cycles.ResultsAmong stage I-IIA disease, twenty (19.6%) patients received 1–3 cycles, and eighty-two (80.4%) patients received at least 4 cycles of adjuvant chemotherapy. Univariate analysis revealed that the patients in 1-3cycles group had not significantly improved 5-year OS and PFS than those in the ≥ 4 cycles group (5-year OS: hazard ratio [HR] 1.21; 95% confidence interval [CI] 0.25– 5.78, p = 0.1), and 5-year PFS: HR 0.79; 95% CI 0.26– 2.34, p = 0.1). In the multivariate analysis, there was no impact of 1–3 versus ≥ 4 cycles of chemotherapy on 5-year OS (HR 1.21, 95% CI 0.25–3.89, p = 0.8) or 5-year PFS (HR 0.94, 95% CI 0.32–2.71, p = 0.9). The potential independent risk factors associated with 5-year OS and PFS included the surgery approach and FIGO stage.ConclusionThe number of cycles of platinum-based chemotherapy could not be associated with a survival benefit for patients with early-stage OCCC.

Trimodality Treatment of Superior Sulcus Non-Small Cell Lung Cancer: An Institutional Series of 47 Consecutive Patients

Treatment of superior sulcus tumors (SST) using concurrent chemoradiation followed by surgery is a current standard. However, due to the rarity of this entity, clinical experience in its treatment remains scarce. Here, we present the results of a large consecutive series of patients treated with concurrent chemoradiation followed by surgery at a single academic institution. The study group included 48 patients with pathologically confirmed SST. The treatment schedule consisted of preoperative 6-MV photon-beam radiotherapy (45-66 Gy delivered in 25-33 fractions over 5-6.5 weeks) and concurrent two cycles of platinum-based chemotherapy. Five weeks after completion of chemoradiation, pulmonary and chest wall resection was performed. From 2006 to 2018, 47 of 48 consecutive patients meeting protocol criteria underwent two cycles of cisplatin-based chemotherapy and concurrent radiotherapy (45-66 Gy) followed by pulmonary resection. One patient did not undergo surgery due to brain metastases that occurred during induction therapy. The median follow-up was 64.7 months. Chemoradiation was well tolerated, with no toxicity-related deaths. Twenty-one patients (44%) developed grade 3-4 side effects, of which the most common was neutropenia (17 patients; 35.4%). Seventeen patients (36.2%) had postoperative complications, and 90-day mortality was 2.1%. Three- and five-year overall survival (OS) were 43.6% and 33.5%, respectively, and three- and five-year recurrence-free survival were 42.1% and 32.4%, respectively. Thirteen (27.7%) and 22 (46.8%) patients had a complete and major pathological response, respectively. Five-year OS in patients with complete tumor regression was 52.7% (95% CI 29.4-94.5). Predictive factors of long-term survival included age below 70 years, complete resection, pathological stage, and response to induction treatment. Chemoradiation followed by surgery is a relatively safe method with satisfactory outcomes.

Abstract CT066: HERTHENA-Lung02: A randomized Phase 3 study of patritumab deruxtecan vs platinum-based chemotherapy in locally advanced or metastatic EGFR-mutated NSCLC after progression with a third-generation EGFR tyrosine kinase inhibitor

Abstract Background: Standard therapies for patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) that has progressed after treatment with third-generation EGFR tyrosine kinase inhibitors (TKIs) offer only limited benefit. Human epidermal growth factor receptor 3 (HER3) is often expressed in primary NSCLC tumors, and HER3 expression is commonly observed in patients with EGFR mutations. HER3-DXd is a novel antibody-drug conjugate composed of a human anti-HER3 monoclonal antibody (patritumab) linked to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. HER3-DXd demonstrated efficacy and safety in a phase 1 study in patients with EGFRm NSCLC that progressed following an EGFR TKI and platinum-based chemotherapy (PBC) (U31402-A-U102; NCT03260491). In previously reported results from dose-escalation/expansion, HER3-DXd 5.6 mg/kg demonstrated a manageable safety profile and promising efficacy (confirmed objective response rate by blinded independent central review [BICR] of 39%, median duration of response of 7.0 months, and median progression-free survival of 8.2 months) in a subset of patients (n=44) with advanced EGFRm NSCLC that progressed after ≥1 line of PBC and a third-generation EGFR TKI. Trial Design: HERTHENA-Lung02 (NCT05338970) is a global, open-label, randomized, phase 3 trial evaluating the efficacy and safety of HER3-DXd vs PBC in patients (≈560) with metastatic or locally advanced nonsquamous NSCLC with an EGFR-activating mutation (exon 19 deletion or L858R) who have received 1 or 2 lines of EGFR TKI treatment including a third-generation EGFR TKI and had disease progression following treatment with a third-generation EGFR TKI. Patients are randomized 1:1 to receive either HER3-DXd 5.6 mg/kg every 3 weeks or 4 cycles of PBC containing pemetrexed (can be continued as maintenance) with cisplatin or carboplatin. Patients are stratified by prior third-generation EGFR TKI treatment (osimertinib vs other), line of prior third-generation EGFR TKI use (first vs second line), region (Asia vs rest of world), and presence of stable brain metastases (yes vs no). The primary endpoint is progression-free survival by BICR (per RECIST v1.1). The key secondary endpoint is overall survival. Other secondary endpoints include investigator-assessed progression-free survival, objective response rate, duration of response, clinical benefit rate, disease control rate, time to response (all assessed by investigator and BICR per RECIST 1.1), safety, and patient-reported outcomes. Enrollment began May 2022 and is ongoing, with sites in Asia, Australia, Europe, and North America. Citation Format: Balazs Halmos, Helena A. Yu, Yi-Long Wu, Makoto Nishio, Martin Reck, David Sternberg, Stephen Esker, Tony Mok. HERTHENA-Lung02: A randomized Phase 3 study of patritumab deruxtecan vs platinum-based chemotherapy in locally advanced or metastatic EGFR-mutated NSCLC after progression with a third-generation EGFR tyrosine kinase inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT066.

Abstract PD11-12: PD11-12 DORA: A Phase II, Multicenter, International, Non-Comparator Study of Olaparib (O) +/- Durvalumab (D) as a chemotherapy-free maintenance strategy in Platinum tReated Advanced Triple-Negative Breast Cancer (aTNBC)

Abstract Introduction: A significant proportion of aTNBC patients carry homologous recombination defects associated with platinum sensitivity. Olaparib is an approved PARP inhibitor (PARPi) for germline BRCA (gBRCA) associated early and metastatic breast cancer as well as maintenance therapy in platinum-sensitive ovarian cancer irrespective of gBRCA status. PARPi enhances immune response via cGAS/STING activation and is synergistic with anti-PD-1 blockade in preclinical models without overlapping toxicities. Here, the efficacy of maintenance olaparib (O) +/- durvalumab (D) in aTNBC patients following clinical benefit from platinum chemotherapy is investigated (NCT03167619). Methods: Eligible pts had aTNBC with investigator-assessed clinical benefit (SD, PR, CR) after a minimum of 3 q3-weekly or 6 q1-weekly cycles of platinum-based chemotherapy in the 1st or 2nd line treatment setting. Patients were randomized 1:1 to receive O 300 mg BID daily or O 300mg BID daily + D 1.5g IV q4 wks. The study was a non-comparator trial; randomization aimed to reduce bias. Tumors were evaluated by RECIST1.1 at baseline and q8 wks. Known gBRCA carriers were limited to 10. The primary endpoint was progression-free survival (PFS). Secondary endpoints were disease control rate (DCR), clinical benefit rate (CBR), and overall survival (OS). Results: From 2/4/2019-12/24/2020, 45 pts were randomized (23 pts in O arm; 22 in O+D arm). 82.2% received platinum as 1st line therapy and 82% received a platinum-doublet. As of data cutoff (6/30/2021), median follow-up of 9.8m (7.2-15.1), the median PFS was 3.95m (p= 0.0023; 95% CI 2.55-6.13) with O monotherapy. The median PFS was 6.1 mos (p= &amp;lt;.0001; 95% CI 3.68-10.11) in the O+D arm. CBR (CR, PR or SD ≥ 24 wks) was 39.1% (19.7%-61.5%) and 36.4% (17.2%-59.3%) in the O and O+D arms, respectively. DCR was 52.2% (30.6%, 73.2%) and 68.2% (45.1%, 86.1%) in the O and O + D arms, respectively. Currently, 7 pts (15.6%) remain on study treatment, only 2 have gBRCA alterations. No new safety signals were reported. Correlative analysis including germline/somatic BRCA, HRR genes, BRCA methylation, TMB and PDL-1 in association with clinical outcomes will be presented. Conclusions: A subset of non-gBRCA altered aTNBC pts who derived clinical benefit from platinum-based chemotherapy had a durable disease control with a chemotherapy-free maintenance strategy of olaparib +/- durvalumab. Citation Format: Sarah L. Sammons, Tira J. Tan, Young Hyunk Im, Tiffany A. Traina, Carey Anders, Ezekiel Renzulli, Sung-Bae Kim, Rebecca Dent. PD11-12 DORA: A Phase II, Multicenter, International, Non-Comparator Study of Olaparib (O) +/- Durvalumab (D) as a chemotherapy-free maintenance strategy in Platinum tReated Advanced Triple-Negative Breast Cancer (aTNBC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD11-12.

Phase II trial of lurbinectedin combined with avelumab as maintenance therapy for metastatic urothelial carcinoma with stable or responding disease following platinum-based chemotherapy.

TPS590 Background: Maintenance avelumab following stable/responding disease after 4-6 cycles of platinum-based chemotherapy is a conventional first-line therapy for metastatic urothelial carcinoma (mUC). Given the attrition of patients between lines of systemic therapy, there is a role for extending the benefits of maintenance avelumab by combinations with tolerable and active agents. Lurbinectedin (Lurbi) is an alkylating agent and selective inhibitor of oncogenic transcription. Lurbi is approved by the US FDA for treating small cell lung cancer with progression on platinum-based chemotherapy with typical dosing as 3.2 mg/m2 intravenously (IV) every 3 weeks. The activity of lurbi in the presence of DNA damage repair (DDR) alterations, multiple transcriptomic drivers and preclinical synergism with and feasibility of co-administration with immune checkpoint inhibitors (ICI) suggests potential activity of combination lurbi and ICI in mUC. Patients with stable or responding disease following platinum-based chemotherapy are phenotypically selected for deficiencies in DDR. Lurbi may be tolerable in this setting given mostly reversible myelosuppression and no serious non-hematologic toxicities especially neurotoxicity. Thus, the combination of lurbi with maintenance avelumab may warrant evaluation in mUC. Methods: A non-randomized multicenter (Advent Health Cancer Institute, Moffitt Cancer Center) phase II trial (n=36) is designed to evaluate combination avelumab (800 mg IV every 2 weeks) and lurbi (3·2 mg/m2 IV as a 1-h infusion every 4 weeks) for those with stable or responding disease following 4-6 cycles of platinum-based first-line platinum-based chemotherapy for mUC. Therapy is continued till progression of disease, intolerable toxicities or patient decision. Patients are seen for a clinical examination every 4 weeks (1 cycle) with laboratory evaluation every 2 weeks. Radiographic imaging is performed every 8 weeks for 6 months and then every 12 weeks thereafter to assess disease. Premedication for lurbi includes corticosteroids (dexamethasone 8 mg or equivalent) and serotonin antagonists. Mandatory granulocyte-colony stimulating factor (G-CSF) prophylaxis will be administered to all patients. Baseline archival tumor tissue and periodic blood is collected for correlative studies (tumor genomics/PD-L1 expression, circulating tumor DNA and immune markers). Given a median progression-free survival (PFS) with avelumab alone of 3.7 months, an alternative median PFS of 6 months is of interest warranting further development. We will enroll 33 evaluable patients to achieve 90% power at a 1-sided alpha level 0.1 to detect hazard ratio of 0.62. Given ~10% of enrolled patients may be inevaluable, we may enroll up to 36 patients. Clinical trial ID: NCT05574504. Clinical trial information: NCT05574504 .