Stage IVB Disease Research Articles

Real-world event-free survival (rwEFS) and overall survival (rwOS) in elderly patients with resected locoregionally advanced head and neck squamous cell carcinoma (LA HNSCC) in the US.

375 Background: Surgery followed by adjuvant radiotherapy (RT) ± systemic therapy (ST) is often recommended for patients (pts) with resectable LA HNSCC with curative intent. This study assessed rwEFS, rwOS, and the correlation between rwEFS and rwOS in elderly pts (≥66 years old at diagnosis) with resected LA HNSCC to better understand unmet needs and inform future clinical trial designs. Methods: This retrospective cohort study utilized linked SEER-Medicare data (2007–2019). Pts with newly diagnosed stage III-IVB (AJCC 6/7th) LA HNSCC (larynx, hypopharynx, oral cavity, or oropharynx) who underwent surgery as primary treatment within 4 months of diagnosis were included. Index date was defined as the primary treatment initiation date. rwEFS was defined as time from index date to first recurrence or death, whichever occurred first. rwOS was defined as time from index date to death. Baseline (12 months prior to index date) factors associated with rwEFS and rwOS were assessed using a Cox proportional hazards model. Correlation between rwEFS and rwOS was assessed using the normal scores rank correlation. Results: A total of 526 pts met the selection criteria (median follow-up: 24.3 months). The median (interquartile range) age at initial diagnosis was 72.6 (68.6-78.8) years, 63.9% were male, 79.5% were white, and 6.1% had stage IVb disease. HPV status and smoking status were not available. Over half of pts received adjuvant RT ± ST following resection. Median rwEFS and 5-year rwEFS were 8.0 months (95% CI: 6.4, 9.2) and 16.3%, respectively. Median rwOS was 32.6 months (95% CI: 26.2, 42.3), with a 5-year rwOS of 37.8%. Older age, primary hypopharynx disease (vs. oropharynx), and higher Charlson Comorbidity Index scores were associated with significantly shorter rwOS. Additionally, surgery followed by RT ± ST (vs. surgery only) and less advanced tumor stage were associated with significantly longer rwEFS and rwOS. The correlation between rwEFS and rwOS was moderate and significantly positive (r = 0.68 [95% CI: 0.62, 0.74], p<0.001). Conclusions: Real-world survival outcomes were modest among elderly pts with surgically managed LA HNSCC, highlighting a population with significant unmet need where more effective therapies are needed. rwEFS was found to have a significant, positive correlation with rwOS, supporting EFS as a predictor for OS in this patient population. Primary treatment and association with rwEFS and rwOS. 1,2,3 Treatment Pattern N (%) HR (95% CI) - rwEFS HR (95% CI) - rwOS Surgery Only 144 (27.4%) - - Surgery followed by RT 172 (32.7%) 0.60 (0.47, 0.78)* 0.77 (0.58, 1.03) Surgery followed by RT + ST 128 (24.3%) 0.49 (0.36, 0.66)* 0.50 (0.34, 0.72)* RT or RT+ST followed by surgery 66 (12.5%) 0.66 (0.47, 0.93)* 0.80 (0.55, 1.18) 1 Treatment modalities with N<11 were not reported. 2 *denotes p < 0.05. 3 denotes reference group.

555. SUPRACLAVICULAR NODE INVOLVEMENT, A NODAL OR METASTATIC DISEASE? - A 10-YEAR EXPERIENCE IN ESOPHAGEAL CARCINOMA AT A TERTIARY REFERRAL CENTRE

Abstract Background Despite the advance in neoadjuvant chemothepray/chemoradiotherapy and favourable outcomes of surgical management in supraclavicular lymph node (SCLN) involvement reported in recent studies, the latest AJCC/UICC TMN classification still regards SCLN metastasis as extra-regional i.e Stage IVB (M1) disease. The role of SCLN dissection and surgical management remain controversial. At National University Hospital of the present study, bilateral supraclavicular lymphadenectomy is routinely performed for resectable thoracic ESCC. The aim of this retrospective cohort study is to investigate the long-term outcome of surgical management in pathological SCLN metastasis and its survival benefit comparing to Stage IIB-IVA diseases. Methods Patients with ESCC who underwent esophagectomy and 3-field lymphadenectomy with curative intent between January 2013 and January 2023 at the single centre were included; cases of salvage esophagectomy post-definitive concurrent chemoradiotherapy, palliative resections, and concurrent head and neck cancers were excluded. Neoadjuvant treatments were considered in cases staged clinically as T2 and/or N1 or greater. Pathological status of lymph nodes was recorded according to JES classification. Demographics and prognostic factors were examined using univariant analysis of overall survival (OS). Patients with SCLN metastases and other LN involvements were compared and OS were analysed using Kaplan-Meier method. Results 544 patients were included. 183 had one or more pathological LN metastasis (pN1:126, pN2 46, and PN3: 11) in which 55 patients had SCLN metastasis. Patients with LN metastasis had poorer prognosis than those without (pN0) with a Hazard Ratio (HR) of 2.68 (95% CI, 1.12-3.40, p<0.01); similar pattern was seen in patients with SCLN metastasis (HR 2.28, p<0.01). The 3-year and 5-year OS of patients with SCLN metastasis was 18.5% and 11.6% respectively whereas those of other LN metastasis was 21.4% and 15.8%; the difference between the groups was not statistically significant (p=0.525) (graph 1). Conclusion Lymph node status (pN) is a well-recognised prognostic factor as reaffirmed, however, within the pN positive cohort, long-term survival of patients with SCLN metastasis, considered as stage IVB (M1), was comparable (p<0.05) to those with other LN metastases. This supports the survival benefit of surgical resection with neoadjuvant therapy in SCLN metastases as following nodal disease treatment algorithm; further evaluation including systemic therapy and lymph node sub-group analysis is being conducted. Whilst randomised controlled trials such as Japanese JCOG2013 provides level I evidence, the present study provides complementary real-world experience for SCLN dissection.

Treatment patterns and prognosis of patients with clear cell adenocarcinoma of the cervix: A population-based cohort study.

To describe treatment patterns and prognoses for clear cell adenocarcinoma of the cervix (CCAC), a poorly understood rare tumor. A retrospective case‒control study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database, focusing on females diagnosed with CCAC between 2000 and 2019. Kaplan‒Meier analysis, propensity score matching, Cox regression analysis, and subgroup analysis were used to assess treatment outcomes and risk factors. Of the 52,153 patients with cervical cancer in the SEER database, 528 had CCAC. Overall survival (OS) was worse for patients with early-stage and locally advanced CCAC disease, although no differences in survival were observed for patients with stage IVB disease compared to those with other histologies. In our investigation into treatment patterns, we have discovered that surgical treatment was the preferred choice for the majority of patients with locally advanced CCAC (58.5%). Further, Kaplan-Meier analysis revealed that surgery improved OS in CCAC patients (65.6% vs. 25.3%, P=0.000), with similar results in locally advanced-stage patients (57.9% vs. 26.7%, P=0.000). Moreover, multivariate Cox regression analysis revealed that surgery was significantly associated with a more favorable prognosis in CCAC patients with locally advanced disease (HR 0.299, 95% CI: 0.153-0.585, P=0.000). Consistent findings were observed following propensity score matching (HR 0.283, 95% CI: 0.106-0.751, P=0.011). According to the subgroup analyses, surgical intervention continued to show a beneficial effect on CCAC patients with locally advanced disease (HR=0.31, 95% CI 0.21-0.46, P<0.001). In particular, we also found that compared to patients who received primary radiotherapy (RT), those with CCAC who underwent radical surgery exhibited a significantly prolonged OS in locally advanced CCAC patients. Furthermore, multivariate Cox regression analysis revealed that surgery was associated with better outcomes in patients with stage IB3-IIA2 and locally resectable stage IIIC patients (HR 0.207, 95% CI=0.043-0.991, P=0.049). However, this trend was not observed for patients with stage IIB-IVA (except locally resectable stage IIIC) CCAC. Surgery should be considered the preferred treatment option for patients with locally advanced CCAC at stage IB3-IIA2 and locally resectable stage IIIC.

Characteristics, treatment patterns, and prognostic factors in small cell lung cancer transformation of advanced non-small cell lung cancer with epidermal growth factor receptor mutation after tyrosine kinase inhibitor therapy.

e20569 Background: Small cell lung cancer transformation in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation following tyrosine kinase inhibitor (TKI) therapy poses a challenging clinical scenario. This study aims to explore the characteristics, treatment patterns, and prognostic factors associated with this transformation. Methods: A total of 41 patients with transformed SCLC (tSCLC) were included. Patient characteristics, treatment details, and laboratory data were collected. Re-biopsy specimens and subsequent treatments were analyzed. Statistical analyses were conducted to identify factors associated with treatment response and survival outcomes. Results: The median age of the patients was 61.7 years old, with a median time from TKI treatment to small cell transformation of 22.2 months. The majority were female (58.5%), never smokers (80.5%), with 53.7% having stage IVB disease prior to EGFR-TKI treatment. The most prevalent initial EGFR mutation was exon 19 deletion (56.1%), and afatinib (46.3%) was the most commonly used EGFR-TKI. EGFR mutation analysis was performed in 68.3% of the tSCLC specimen, and acquired T790M was detected in 7.1% of the patients. Treatment patterns after transformation included various systemic therapies, with the most (63.4%) receiving etoposide plus platinum (EP) based chemotherapy in the first line setting. Among all the patients, 56.1% received EGFR-TKI and 22% received immune checkpoint inhibitors (ICI) throughout the post-transformation treatment course. Anemia (Hgb &lt; 10g/dL) and ever use of EP were significant factors associated with post-transformation survival. The median progression-free survival (PFS) of the first line treatment was 3.27 months, and the overall survival (OS) was 10.43 months post transformation. Conclusions: Small cell lung cancer transformation in advanced NSCLC with EGFR mutation after TKI therapy is associated with diverse clinical characteristics and dismal outcomes. We presented the complexity of managing these cases in real-world practice. Anemia and ever use of EP affected post-transformation survival. Further research is warranted to optimize therapeutic strategies for this unique subset of patients.

Prognostic performance of the 2023 FIGO staging schema for endometrial cancer

ObjectiveTo assess the prognostic performance of the 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging schema. MethodsThis retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. Study population was 129,146 patients with stage I-IV endometrial cancer per the 2009 FIGO staging schema. Stage-shifting and overall survival (OS) were assessed according to the 2023 FIGO staging schema. ResultsUpstage (IA → II, 21.4 %; IB → II, 53.0 %) and downstage (IIIA→IA3, 22.2 %) occurred in both early and advanced diseases. Inter-stage prognostic performance improved in the 2023 schema with widened 5-year OS rate difference between the earliest and highest stages (68.2 % to 76.9 %). Stage IA1-IIB and IIC had distinct 5-year OS rate differences (85.8–96.1 % vs 75.4 %). The 5-year OS rate of the 2009 stage IIIA disease was 63.9 %; this was greater segregated in the 2023 schema: 88.0 %, 62.4 %, and 55.7 % for IIIA→IA3, IIIA1, and IIIA2, respectively (inter-substage rate-difference, 32.3 %). This 5-year OS rate of stage IA3 disease was comparable to the 2023 stage IB-IIB diseases (88.0 % vs 85.8–89.5 %). In the 2023 stage IIIC schema (micrometastasis rates: 29.6 % in IIIC1 and 15.6 % in IIIC2), micrometastasis and macrometastasis had the distinct 3-year OS rates in both pelvic (IIIC1-i vs IIIC1-ii, 84.9 % vs 71.1 %; rate-difference 13.8 %) and para-aortic (IIIC2-i vs IIIC2-ii, 82.9 % vs 65.2 %; rate-difference 17.7 %) nodal metastasis cases. The 5-year OS rate of the 2009 stage IVB disease was 23.4 %; this was segregated to 25.4 % for stage IVB and 19.2 % for stage IVC in the 2023 staging schema (rate-difference, 6.2 %). ConclusionThe 2023 FIGO endometrial cancer staging schema is a major revision from the 2009 FIGO schema. Almost doubled enriched sub-stages based on detailed anatomical metastatic site and incorporation of histological information enable more robust prognostication.

Outcomes of patients with advanced epithelial growth factor receptor mutant lung cancer treated with first-line osimertinib who would not have met the eligibility criteria for the FLAURA clinical trial

ObjectivesOsimertinib is largely used as first-line therapy for metastatic epithelial growth factor receptor (EGFR) mutant lung cancers based on the FLAURA clinical trial. Real-world patient outcomes often differ from clinical trial outcomes. This study evaluated the efficacy of first-line osimertinib in patients treated in British Columbia (BC), Canada. Furthermore, we compared the outcomes of patients who would and would not have been eligible for the original FLAURA trial. MethodsConsecutive patients receiving first-line osimertinib for metastatic EGFR exon19 or L858R lung cancer were identified using the BC Cancer Pharmacy Database. Patient eligibility for the FLAURA clinical trial were retrospectively reviewed based on the following criteria: ECOG ≥ 2, symptomatic brain metastases or on steroids, hemoglobin < 90 g/L, platelets < 100x109/L, or a creatinine clearance < 50 mL/min. mOS was assessed for the entire population and compared between patients who would have been eligible and ineligible for FLAURA. ResultsFrom January 2020 to October 2021, 311 patients received first-line osimertinib; 44 % (137/311) were deemed FLAURA ineligible, predominantly due to low ECOG (n = 120). After a median follow-up of 26.5 months, the mOS for the entire cohort was 27.4 months (95 %CI 23.8–30.1). The mOS for ineligible patients was 18 months shorter than eligible patients (15.8 vs 34.2, p < 0.001). Ineligible patients had higher rates of de novo stage IV disease, higher rates of stage IVB disease, and more sites of disease than eligible patients. ConclusionIn this real-world population, nearly half of patients would have been ineligible for FLAURA. The mOS was one year shorter than reported in FLAURA. However, patients who would have been eligible for the FLAURA clinical trial had similar OS to patients enrolled in FLAURA. Trial ineligible patients had a higher burden of disease at baseline which may have led to inferior outcomes. Further research is needed to improve outcomes in these patients.

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes

ObjectiveVaginal carcinoma is a rare malignancy accounting for 1–2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy–chemotherapy followed by interventional radiotherapy is considered a valid alternative....

QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial.

QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.

Primary tumor consolidative therapy improves the outcomes of patients with advanced EGFR-mutant lung adenocarcinoma treated with first-line osimertinib.

Patients with advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (LAD) inevitably experience drug resistance following treatment with EGFR-tyrosine kinase inhibitors (TKIs). We aimed to analyze the effect of primary tumor consolidative therapy (PTCT) on patients treated with first-line osimertinib. This retrospective cohort study was conducted in patients with advanced stage III or stage IV LAD with EGFR-sensitizing mutations (exon 19 deletion or L858R mutation) with disease control after first-line osimertinib. A curative dose of primary tumor radiotherapy or primary tumor resection was classified as PTCT. We compared the progression-free survival (PFS) and overall survival (OS) of patients with and without PTCT. This study included 106 patients with a median age of 61.0 years, and of those, 42% were male and 73.6% were never-smokers. Exon 19 deletion was observed in 67.9%, 30.2% had a programmed cell death ligand 1 (PD-L1) tumor proportion score <1%, 33.0% had brain metastasis, and 40.6% had oligometastasis. In all, 53 (50%) patients underwent PTCT. Patients who underwent PTCT demonstrated significantly better PFS [30.3 (95% confidence interval (CI), 24.1-36.4) versus 18.2 (95% CI, 16.1-20.2) months; p = 0.005] and OS [not reached versus 36.7 (95% CI, 32.5-40.9) months; p = 0.005] than patients who did not. A multivariate analysis showed that PTCT was an independent factor associated with better PFS [hazard ratio (HR), 0.22; 95% CI, 0.10-0.49; p < 0.001] and OS [HR, 0.10; 95% CI, 0.01-0.82; p = 0.032]. The PFS benefits of PTCT were consistent across subgroups, and the HR tended to be lower in patients aged <65 years, males, smokers, stage IVB disease, L858R, PD-L1 expression ⩾1%, non-oligometastasis, and brain metastasis. Of the patients with advanced EGFR-mutant LAD, those who underwent PTCT had a significantly better survival outcome than those who did not. The survival benefits were consistent across different subgroups.

Abstract B112: Disparities in cervical cancer survival among Hispanic subpopulations living in the United States

Abstract Purpose: The Hispanic population bears a high burden of cervical cancer; however, disaggregated data, which is vital in equitable resource allocation, lacks in this group. Our study evaluated disparities in cervical cancer survival among Hispanic subpopulations receiving guideline-concordant care and identified factors affecting survival. Methods: Data from the National Cancer Database was used to identify patients with cervical cancer from 2004-2019. The Hispanic cohort was analyzed in its entirety, and by region of origin. Nine quality metrics were established to assess guideline-concordant care for eligible patients across various cancer stages. Demographic data, treatment modalities, and survival were described. Demographic and clinical variables were stratified by Hispanic subpopulation and compared using chi-squared tests. Kaplan-Meier curves were employed to examine cervical cancer survival among the Hispanic subpopulation for each quality metric. Marginal Poisson log-linear models were utilized to evaluate the association Hispanic subpopulation and the receipt of eligible quality metrics, and obtain adjusted relative risks (aRR), while controlling for potential confounders. Results: A total of 77,567 patients were included, 4363 (5.6%) of which identified as Hispanic. Compared to non-Hispanic White (NHW) and non-Hispanic Black (NHB) populations, larger proportion of the Hispanic population was uninsured (19.16%, p &amp;lt; 0.001) and more likely to live in neighborhoods with lowest rates of high school diploma attainment (61.43%, p &amp;lt;0.001). Significant differences in neighborhood income, education level, insurance status, and stage at presentation among Hispanic subpopulations were identified (p&amp;lt;0.001). Survival among patients with stage IA2-IIA2 patients undergoing radical hysterectomy was lowest among NHB and Cuban patients when compared to NHW and other Hispanic patients (p&amp;lt;0.001). Survival among stage IB2-IVA patients undergoing primary radiation and concurrent chemotherapy was also lowest among Cuban, NHW and NHB patients when compared to other populations, and highest among Mexican populations (p&amp;lt;0.001). Among patients with stage IVB disease receiving chemotherapy, Dominican populations had the highest survival rates p&amp;lt;0.001). Compared to Mexican patients, Cuban patients were 1.18 times as likely to receive timely initiation of treatment in early stage (RR 1.18, 95% CI 1.03-1.34, p=0.01). Patients of South or Central American origin (RR 1.18, 95%CI 1.09-1.28, p&amp;lt; 0.001), Cuban (RR 12.5, 95%CI 1.1-1.43, p&amp;lt;0.001), and Dominican (RR1.19, OR 1.01-1.4, p=0.03) were more likely to undergo timely initiation of treatment in locally advanced disease when compared to Mexican patients. Conclusion: Significant differences in survival outcomes for patients with cervical cancer were identified among our cohort, as well as within the Hispanic population. Variation in initial of treatment, treatment type received, and social factors may contribute to these disparities. Citation Format: Andreea Dinicu, Shayan Dioun, Yongzhe Wang, Yongmei Huang, Jason Wright, Ana Tergas. Disparities in cervical cancer survival among Hispanic subpopulations living in the United States [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B112.

Lacutamab in Patients with Relapsed and Refractory Sèzary Syndrome: Results from the Tellomak Phase 2 Trial

Introduction Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin lymphoma. Sézary syndrome (SS) is a rare, aggressive and advanced type of CTCL. It has a unique biology, with high expression of KIR3DL2, a killer immunoglobulin-like receptor, reported in more than 85% of patients. SS is characterized by erythroderma, significant blood involvement with malignant SS cells, and lymphadenopathy. These patients suffer from debilitating itching and recurrent skin infections, often affecting quality of life (QoL). SS is distinguished by its poor prognosis, as the median survival of patients is approximately 5 years. Lacutamab is a first-in-class monoclonal antibody designed to specifically deplete KIR3DL2-expressing cells via antibody-dependent cell-cytotoxicity and phagocytosis. Methods TELLOMAK is an international, open-label, Phase 2 trial with multiple cohorts (NCT03902184). We report here results from Cohort 1, designed to evaluate safety and efficacy of single agent lacutamab in patients with relapsed/refractory (R/R) SS after at least 2 prior systemic therapies including mogamulizumab. Patients had blood stage B2 (≥1000 circulating Sézary cells/mm 3) at screening based on central evaluation by flow cytometry. Patients with evidence of large cell transformation were excluded. Lacutamab 750 mg is administered as an intravenous infusion weekly × 5 weeks (w), every 2 w × 10, then every 4 w until progression or unacceptable toxicity. Primary endpoint was Objective Response Rate (ORR) by global response score based on the evaluation of 4 compartments: skin, blood, lymph nodes and viscera according to International Consensus criteria (Olsen 2011). Secondary endpoints included but not limited to additional efficacy endpoints, safety, QoL assessments. Results At the data cut-off of May 1, 2023, 56 SS patients were enrolled treated and evaluated in Cohort 1. Median age was 69 years (range: 42-86), the median prior lines of systemic therapies was 6.0 (range: 2-15), 60.7 % (n=34) had stage IVA1, 32.1 % (n=18) had stage IVA2 and 7.1% (n=4) had stage IVB disease at baseline, all patients (100%) had blood involvement (B2), 67.9% (n=38) had confluence of erythema covering ≥ 80% body surface area (T4), 35.7% (n=20) had lymph node lymphoma involvement (N3). Median follow-up was 14.4 months (95% CI 9.0-18.4). In the ITT population (n=56), Global confirmed ORR was 37.5% (n=21; 95% CI 26.0-50.6) including 2 CRs, with a median time to response of 2.8 months (range 1-9; Figure 1). Confirmed ORR in skin was 46.4% (n=26; 95% CI 34.0-59.3) including 5 CRs. Confirmed ORR in blood was 48.2% (n=27; 95% CI 35.7-61.0) including 15 CRs. Clinical Benefit Rate (CBR, defined as CR+PR+SD) was 87.5 % (n=49; 95% CI 76.4-93.8). Median PFS was 8.0 months (95% CI 4.7-21.2). Grade ≥ 3 Treatment-related (TR) Treatment-Emergent Adverse events (TEAEs) were observed in 10/56 (17.9%) pts, Serious TR TEAEs were observed in 4/56 (7.1%) and 3/56 (5.4%) pts discontinued study drug due to TR TEAE. Data from additional key endpoints will be presented. Conclusion In this SS cohort from the TELLOMAK study, our data confirm that lacutamab monotherapy shows promising clinical activity in a R/R population previously treated with 2 or more prior systemic therapies including mogamulizumab, and an overall favourable safety profile. Continued evaluation of this new targeted treatment option for patients with SS is warranted.

Optimum Radiation Dose for Palliation in Head and Neck SCC: A Phase III Randomized Controlled Trial (OPRAH)

Palliative radiotherapy has been used to alleviate symptoms in locally advanced (T4b) head and neck Squamous cell carcinoma, but optimum dose is still debated. The trial has been designed to determine if high palliative radiation dose (30 Gy/ 5#/ 5 days) improves progression free survival compared to low palliative dose (20 Gy/ 5# 5 days). The secondary objective was to compare toxicity rates profile between the two radiation doses (CTCAE version 5) and compare Quality of life between the two arms with QOL - HN35 questionnaire. This is a prospective randomized phase III randomized controlled trial. We hypothesized that by increasing the dose per fraction and total dose there would be an improvement in PFS without difference in late toxicity and QOL. The present study will also perform an exploratory analysis of effect of palliative radiotherapy on immune function and its effect on survival. Considering median PFS 2.5 months in 20 Gy arm we assumed that PFS will improve by 1.25 months (total PFS 3.75 months) in 30 Gy arm. To reach the hypothesis with 90% power and alpha error of 0.05, attrition rate of 10% sample size calculated was 286. Patients with cT4b disease of larynx/ Hypopharynx/ Oropharynx/ Oral cavity not amenable to surgery, Carotid encasement > 180 degree, histologically proven squamous cell carcinoma, Age > 18 years and < 75 years ECOG PS 0-2 were eligible. Until December 2022, we completed accrual of 239 patients. Median age: 53 years (Range: 29-70 years); Gender: Male: Female = 9: 1 (214: 25). 145 patients had history of smoking, 87 had additional history of tobacco chewing. 67 patients had history of alcohol consumption, 13 patients had history of smoking, tobacco and alcoholism. All patients had stage IVA or Stage IVB disease. Primary site was oral cavity in 58%, Oropharynx in 19%, larynx in 10% and hypopharynx in 8% cases. 72.3% patients had a PS of 1, 21.7% had PS 2 at presentation. Prior to RT requirement of analgesic was: No pain medicine: 5; WHO step I:173, WHO step II: 52, WHO step III:14. All patients received conformal radiation with 6 MV linear accelerator. Target volume was GTV plus 1 cm margin to form CTV and 5 mm expansion to generate PTV. Out of 239 patients 67 patients had a disease progression. Mucositis is the commonest side effect affecting most of the patients and improve with best supportive care. High dose palliation appears to be equally well tolerated. However, the impact of such dose escalation will be established if final analysis reaches the pre-defined endpoint.

Statement of the Uterus Commission of the Gynecological Oncology Working Group (AGO) on the Use of Primary Chemoimmunotherapy to Treat Patients with Locally Advanced or Recurrent Endometrial Cancer.

The publication of two large randomized studies - the ENGOT-EN-6-NSGO/GOG-3031/RUBY trial and the NRG-GY018 trial - which investigated combining chemotherapy with immunotherapy to treat patients with primary advanced or recurrent endometrial cancer (EC) has transformed the clinical study landscape in terms of first-line therapy for affected patients and has set a new standard of therapy. In the ENGOT-EN-6-NSGO/GOG-3031/RUBY trial, the addition of dostarlimab to standard chemotherapy with carboplatin and paclitaxel resulted in a significant and clinically relevant improvement of progression-free survival and overall survival in the overall population, a significant and clinically relevant improvement of progression-free survival and overall survival in the subgroup with dMMR/MSI-high tumors, and a significant and clinically relevant improvement of progression-free survival in the subgroup with pMMR/MSI-low tumors. In the NRG-GY018 trial, the addition of pembrolizumab to standard chemotherapy with carboplatin and paclitaxel resulted in a significant and clinically relevant improvement of progression-free survival in the group with dMMR tumors, and a significant and clinically relevant improvement of progression-free survival in the group with pMMR tumors. As expected, the effect in both trials was much more pronounced in the group of patients with dMMR/MSI-high tumors. According to the assessment of the Uterus Organ Commission of the AGO, all patients with dMMR/MSI-high tumors should receive chemoimmunotherapy and all patients with pMMR/MSI-low tumors who meet the inclusion criteria of the two trials discussed here may have chemoimmunotherapy. For dostarlimab this means: patients with EC recurrence who will not undergo surgery or radiotherapy, patients with stage IIIA, IIIB or IIIC1 disease and a measurable lesion postoperatively, patients with stage IIIA, IIIB or IIIC1 disease with histological findings of serous EC, clear-cell EC or carcinosarcoma with or without a measurable lesion postoperatively, and patients with stage IIIC2 or IV disease with or without a measurable lesion postoperatively. For pembrolizumab this means: patients with EC recurrence (except carcinosarcoma) who will not undergo surgery or radiotherapy, and patients with stage III or IVA disease (except carcinosarcoma) and a measurable lesion postoperatively or with stage IVB disease with or without a measurable lesion.

The right time for change: A report on the heterogeneity of IVB endometrial cancer and improved risk-stratification provided by new 2023 FIGO staging criteria

ObjectiveWe sought to provide a contemporary report on stage IVB endometrial carcinoma (2009 FIGO criteria) and applied the 2023 FIGO staging criteria to this population. MethodsRetrospective review of patients who underwent cytoreduction for stage IVB endometrial carcinoma (2009 FIGO criteria) from 2014 to 2020 was performed. Demographics, clinicopathologic factors, and outcomes were recorded. Disease burden and distribution were determined by imaging, operative notes, and pathology reports. Patients were re-staged according to 2023 FIGO staging criteria. Categorical variables were compared using χ2 or Fisher's exact test, and Kaplan-Meier curves compared survival outcomes using the log-rank test. ResultsEighty-eight cases were included. Most patients (63.6%) were not suspected to have stage IVB (2009 FIGO criteria) disease prior to surgery. Seventy-two percent of patients underwent primary cytoreduction, and 12 (19%) were suboptimal. Median progression-free survival (PFS) was 12 months (95% CI 10–16 months), and median overall survival (OS) was 38 months (95% CI 19–61 months). Degree of cytoreduction (p = 0.0101) and pelvic-confined metastatic disease (p = 0.0149) were significant prognostic factors, while distant metastases were not associated with worse outcomes. For those patients who underwent primary cytoreduction, number (p = 0.0453) and diameter (p = 0.0192) of tumor deposits were associated with PFS. When 2023 FIGO staging criteria were applied, 58% of patients underwent change in stage, and 8% did not meet criteria for complete staging. PFS was significantly different based on 2023 FIGO staging (p = 0.0307); a trend in OS was also noted (p = 0.0550). ConclusionStage IVB endometrial carcinoma (2009 FIGO criteria) encompasses a diverse cohort of patients, where certain clinicopathologic features, tumor burden, and degree of cytoreduction are associated with outcomes. The 2023 FIGO staging criteria significantly improves our ability to risk-stratify patients.

Tislelizumab plus chemotherapy in patients with advanced brain metastases of non-squamous non-small cell lung cancer: A multicenter, prospective, open-label phase 2 study.

9080 Background: Patients (pts) with brain metastases (BM) were usually unrepresented in clinical trials assessing the efficacy of PD-(L) 1 inhibitors. Here, we investigated the efficacy and safety of tislelizumab (TIS) plus chemotherapy in NSCLC pts with asymptomatic untreated BM or with stable BM after local radiotherapy. Methods: This multicenter, prospective, open-label phase 2 study enrolled systemic treatment-naïve pts with stage IV non-squamous (nsq) NSCLC without EGFR or ALK mutations who had BM. Pts received TIS combined with pemetrexed and carboplatin for 4 cycles, followed by maintenance TIS and pemetrexed. RECIST v1.1 and RANO-BM were applied for assessment for systematic and brain disease, respectively. The primary endpoint was the investigator-assessed 1-year PFS rate per RECIST v1.1. Results: 36 pts were enrolled with 77.8% having stage IVB disease, 25.0% liver metastases and 41.7% bone metastases. 29 (80.6%) pts were with untreated, asymptomatic brain metastases, and the other 7 (19.4%) received radiotherapy for BM previously. As of 30 Nov 2022, the median follow-up was 12.3 months. 1-year systematic PFS rate was 36.8% (95% CI, 18.0-55.7), with median PFS of 7.5 months (95% CI, 5.1-NE). Systematic ORR was 50.0% (95% CI, 31.9-68.1%). Median OS was not reached, with 1-year OS rate of 70.5% (95% CI, 51.7-83.1). For intracranial efficacy assessment per RANO-BM, 1-year intracranial PFS (iPFS) rate was 56.6 % (95% CI, 31.7-75.5), with 45.5% (95% CI, 19.4, 68.5) and 100% in pts with untreated and pretreated BM, respectively. Intracranial ORR was 56.7% (95% CI, 37.4-74.5%), with 53.8% (95% CI, 33.4-73.4%) in pts with untreated BM and 75% (95% CI, 19.4-99.4%) in pretreated BM. No grade 5 toxicities were observed. Grade 3-4 TRAEs occurred in 33.3% (12/36) of pts. 13.9% of pts experienced irAEs; grade 3-4 irAEs occurred in 2 (5.6%) pts. Conclusions: TIS plus chemotherapy yielded promising systematic and intracranial PFS, and was generally well tolerated in nsq-NSCLC pts with untreated or pretreated BM. Clinical trial information: NCT04507217 . [Table: see text]

Induction and concomitant chemoradiotherapy (CCRT) using modified TPF (docetaxel, cisplatin and 5-FU) for the patients with stage IVB advanced head and neck cancer.

e18031 Background: Efficacy of TPF chemotherapy has been reported mainly in the induction chemotherapy (IC) for head and neck squamous cell carcinoma (HNSCC) so far. The aim of this study was to determine the safety and efficacy of CCRT using modified TPF protocol in patients with Stage IVB HNSCC. Methods: Patients with previously untreated, histologically proven Stage IVB disease of the head and neck were eligible for the study. Twenty-six patients of the HNSCC were enrolled between January 2018 and October 2021 including 6 HPV(-) oropharyngeal, 5 hypopharyngeal, 4 ethmoid, 4 maxillary, 2 primary unknown and 5 other cancers. There were 14 T4b and 13 N3b tumors. CCRT consisted of radiotherapy administered once daily to a total dose of 70 Gy, concomitant with 120-hour infusions of 5-FU (600 mg/m2/day), Docetaxel (50 mg/m2, day 2) and Cisplatin (60 mg/m2, day 2) given during first and fifth week of radiotherapy. These drug doses were determined from the results of our former phase I study to assess the dose limiting toxicity of this protocol. Median follow-up period was 21 months. Results: Eight patients with Stage IVB HNSCC underwent IC and CCRT with this modified TPF protocol. Eight patients underwent CCRT using 2 courses of modified TPF. Five patients underwent CCRT with CDDP, three of them underwent arterial infusion of CDDP by super-selective angiography via external carotid artery. Three other patients underwent CCRT using other protocols and two underwent RT without chemotherapy. Bone marrow suppression was the most common adverse event observed through this study. Although all patients showed dermatitis and mucositis at any grade, other grade 3 or 4 adverse events in these patients were not common. Complete response was obtained in all patients except four patients. The progression-free and over-all survival rates at 24 months of all the patients with Stage IVB HNSCC in our series were 53.4% and 59.1%, respectively. Those of the patients who underwent IC and CCRT with modified TPF protocol were 58.3% and 80.0%, respectively and significantly better than those of the patients with other treatment protocols. Conclusions: Our results suggested that IC followed by CCRT using modified TPF was feasible and very effective in patients with Stage IVB HNSCC.

The Role of Neutrophil-to-Lymphocyte Ratio in Advanced EGFR-Mutant NSCLC Patients Treated with First-Line Osimertinib.

Although serum neutrophil-to-lymphocyte ratio (NLR) is correlated with the outcome of various cancer types, its role in treatment-naïve, advanced, epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with osimertinib remains uncertain. We have the intention to use this biomarker to evaluate the outcomes in NSCLC. Advanced EGFR-mutant NSCLC patients receiving osimertinib as the first-line treatment were included. We evaluated the prognostic role of baseline NLR and explored its association with patients' characteristics. A high NLR was defined as pretreatment serum NLR ≥ 5. A total of 112 eligible patients were included. The objective response rate was 83.7%. The median progression-free survival (PFS) and overall survival (OS) were 20.5 months (95% CI 14.5-26.5) and 47.3 months (95% CI 36.7-58.2), respectively. A high NLR predicted an inferior PFS (HR 1.90 [95% CI 1.02-3.51], P = 0.042) and OS (HR 3.85 [95% CI 1.39-10.66], P = 0.009). Patients with stage IVB disease were more likely to have a high baseline NLR than those with stage IIIB-IVA (33.9% vs 15.1%, P = 0.029). Other patients' characteristics did not correlate with the baseline NLR significantly. Patients with a high NLR had significantly more metastatic organs than those with a low NLR (2.5 ± 1.3 vs 1.8 ± 0.9, P = 0.012), particularly brain, liver, and bone metastasis. There was no significant association between NLR and intrathoracic metastasis. Baseline serum NLR could act as an important prognostic marker for EGFR-mutant NSCLC patients receiving first-line osimertinib. A high NLR was associated with higher metastatic burden, more extrathoracic metastases, and therefore, a worse outcome.

Abstract 964: Genomic and clinical predictors of early disease progression and chemoimmunotherapy benefit in advanced NSCLC

Abstract Background: Immune checkpoint inhibitors (ICIs) as monotherapy (ICI-mono) or with chemotherapy (ICI-chemo) are standard first-line treatment in NSCLC patients lacking targetable driver mutations. Biomarkers to identify patients at risk for early progression on ICI-mono or those who would maximally benefit from upfront ICI-chemo have not been defined. Methods: We queried the GEMINI database to identify metastatic NSCLC patients without targetable EGFR/ALK alterations who were treated with ICI-mono or ICI-chemo. Mutational profiling was performed on tissue or blood using targeted NGS. Outcome measures were defined as clinical progression free survival (PFS) or early progressive disease (PD) rate (defined as rate of 3-month progression), and their association with variables was assessed via Cox Proportional Hazards regression (PFS) or logistic regression (early PD). Predictive deep learning models were used to integrate clinicopathological factors and genomic profile. Results: 735 patients were included in this study, 269 treated with ICI-chemo and 466 with ICI-mono; 446 were treated in the first-line setting. TP53 was the most frequently altered gene (60%), followed by KRAS (37%), AR (21%), and STK11 (19%). In ICI-mono patients, alterations in STK11, ERBB2, ARID1A and CDK6 were associated with a higher likelihood of early PD; only STK11 was associated with early PD (29% vs 17%, P = 0.04) on ICI-chemo. In all patients, low PD-L1 expression and high disease burden (stage IVb and liver metastases) associated with early PD, but there were borderline significant treatment effects in favor of ICI-chemo in never smokers and patients with liver metastases and stage IVb. Shorter PFS was observed in the ICI-chemo group who had CDKN2A alterations vs wild type (median PFS: 5.1 vs 9.0 months; HR: 1.72; P = 0.01). A subgroup analysis of patients with CDKN2A alterations demonstrated preferentially worse outcomes in ICI-chemo compared to ICI-mono, with the best PFS achieved in the ICI-mono treated patients with CDKN2A point mutation. Integration of clinicogenomic features into a multivariate model with feature selection to predict early PD demonstrated a predictive performance of AUC 0.73 (vs PD-L1 alone, AUC 0.60) in the ICI-mono group, driven by liver metastases, stage IVb disease, PD-L1 expression, and STK11 alterations. These features were less predictive in ICI-chemo-treated patients, indicating a protective effect against early PD in these patients from combination chemoimmunotherapy. Conclusions: Low PD-L1, high disease burden, and STK11 alterations are markers of early PD on ICI-mono, and patients with these features may particularly benefit from upfront combination treatment with ICI-chemo to protect against early progression. Citation Format: Lingzhi Hong, Muhammad Aminu, Xuetao Lu, Maliazurina B. Saad, Pingjun Chen, Waree Rinsurongkawong, Amy Spelman, Yasir Y. Elamin, Marcelo V. Negrao, Ferdinandos Skoulidis, Carl M. Gay, Tina Cascone, Mara B. Antonoff, Boris Sepesi, Jeff Lewis, Don L. Gibbons, Ara A. Vaporciyan, Xiuning Le, J.Jack Lee, Sinchita Roy-Chowdhuri, Mark J. Routbort, John V. Heymach, Jia Wu, Jianjun Zhang, Natalie I. Vokes. Genomic and clinical predictors of early disease progression and chemoimmunotherapy benefit in advanced NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 964.

Outcomes associated with treatment to all sites of disease in patients with stage IVB cancer of the cervix

ObjectiveThe use of chemoradiation in patients with stage IVB cancer of the cervix was evaluated to determine if definitive treatment offers benefit.MethodsA database of 546 patients with cancer of the...

High-dose continuous-infusion ifosfamide in advanced thymic epithelial Tumors: A TYME network study

BackgroundWe reported the efficacy and safety results of high-dose, continuous-infusion Ifosfamide,in patients with advanced thymoma (TM) and thymic carcinoma (TC). MethodsThis was a multicentric, prospective study in patients with advanced TM or TC, who had progressed after at least one line of platinum-based chemotherapy. Previous treatment with an anti-angiogenesis or anti-PD(L)1 was allowed.Patients received Ifosfamide (1 g/m2/day) and sodium-2-mercaptoethanesulfonate (1 g/m2/day), as continuous infusion, via a portable pumps for 14 consecutive days.Treatment was administered every 4 weeks until progression or unacceptable toxicity, up to a maximum of 6 cycles.The primary endpoint was the overall response rate (ORR) assessed by RECIST1.1.Secondary endpoints included disease control rate (DCR), Progression-free survival (PFS), overall survival (OS), and safety. ResultsEighteen patients were enrolled from October 2020 to January 2022.Twelve patients had a TC, 5 a TM and 1 a mixed TM/TC. Sixty-one percent of patients (11/18) had stage IVB disease according to Masaoka-Koga, and 39% (7/18) had an ECOG-PS 2. The median number of previous lines of therapy was 2 (range:1–5), and 72% (13/18) and 61% (11/18) of patients were pretreated with an anti-angiogenesis drug and an anti-PD(L)1 drug respectively.The ORR and the disease control rate (DCR) were 28 % (95 %CI: 10 %-53 %) and 67 % (95 %CI: 41 %-86 %), respectively.The median follow-up for PFS was 17.3 months (95 %CI: 4.3-NA), and median PFS was 5.4 months (95 %CI: 2.9–6.4). The median duration of response and SD was respectively 19.6 months (95 %CI: 3.5-NA) and 6.0 months (95 % CI: 3.8–6.4).In patients with TC, the ORR and DCR were 15 % (95 % CI: 2 %-45 %) and 54 % (95 % CI: 25 %-81 %), respectively. In the subgroup of 5 patients with TM, 2 PR and 3 SD were observed.Most patients had only mild (grade 1–2) AEs, the most common being nausea and vomiting (39%; 7/18) and transaminases elevation (33%; 6/18).Twenty-two percent of patients (4/18) experienced an AEs of grade 3 and required ifosfamide dose reduction. No patients had severe AEs. ConclusionHigh-dose continuous-infusion Ifosfamide can be considered as a valuable treatment option in patients with advanced thymic epithelial tumors.