1L Platinum-based Chemotherapy Research Articles

Avelumab First-Line Maintenance for Locally Advanced or Metastatic Urothelial Carcinoma: Results From the Real-World US PATRIOT-II Study

IntroductionIn JAVELIN Bladder 100, avelumab first-line maintenance (1LM) improved overall survival (OS) and progression-free survival (PFS) in patients with locally advanced/metastatic urothelial carcinoma (la/mUC) without progression following 1L platinum-based chemotherapy (PBC) versus best supportive care. PATRIOT-II describes real-world outcomes with avelumab 1LM. Patients and MethodsThis observational, retrospective study of avelumab 1LM in US community/academic centers used medical record data collected from avelumab initiation for ≥12 months to assess survival, safety, and healthcare resource utilization; analyses are descriptive. ResultsThe study included 160 patients from 37 centers (median age, 70 years; 77% male). Avelumab 1LM was initiated at a median of 4 weeks (IQR 3-6) after PBC completion. Median follow-up from avelumab 1LM was 16 months (IQR 11-21). At study end, 19.4% of patients continued avelumab; 73.7% had discontinued due to progression, adverse events (AEs), or performance status deterioration. Median PFS and OS from avelumab initiation were 5.4 months (95% CI, 3.8-6.9) and 24.4 months (95% CI, 20.4-28.4), respectively. Grade ≥3 treatment-related AEs (TRAEs) occurred in 15 patients (9.4%); 35 (21.9%) had any-grade immune-related AEs, and 23 (14.3%) received high-dose systemic corticosteroids for AEs. Forty-four patients (27.5%) were hospitalized during the avelumab treatment period, of whom 13 (8.1%) were hospitalized due to TRAEs. Limitations of this study include a small sample size, potential selection bias, and missing/unknown data. ConclusionThese results align with the JAVELIN Bladder 100 clinical trial and other real-world studies, supporting avelumab 1LM use in patients with la/mUC without progression following 1L PBC.

Real-world (rw) treatment (tx) patterns and clinical outcomes among patients (pts) with metastatic urothelial carcinoma (mUC) receiving first-line (1L) systemic tx and avelumab 1L maintenance (1LM): Results from the IMPACT UC-III study.

390 Background: Avelumab 1LM is a standard of care for pts with mUC that has not progressed after 1L platinum-based chemotherapy (PBC). Immuno-oncology (IO) monotherapy is considered in pts with mUC who are ineligible to receive PBC. Recently approved 1L tx options include enfortumab vedotin + pembrolizumab and nivolumab + gemcitabine/cisplatin. This US retrospective study examined pt characteristics, tx patterns, and clinical outcomes among pts with mUC receiving 1L tx, including avelumab 1LM. Methods: Pts with mUC (bladder cancer; stage IIIB or IV, or ≥2 claims with ICD-10 diagnoses for metastatic cancer) aged ≥18 years, who initiated 1L tx (index date) from Jan 1, 2020 to Jul 31, 2023, were identified from the Healthcare Integrated Research Database (HIRD®; claims and clinical data from the health plan’s Cancer Care Quality Program). Clinical outcomes, including time to next tx (TTNT; time from 1L tx initiation to second-line tx) and overall survival (OS), were evaluated post index date. Pt characteristics and tx patterns were summarized using descriptive statistics. Avelumab 1LM use was identified on/after June 30, 2020 and ≤90 d after 1L PBC discontinuation. OS from the start of 1L tx or 1LM was analyzed using Kaplan-Meier methodology. Results: Of 2,820 pts with mUC, 1L tx was PBC in 37.0% (n=1,044), IO monotherapy in 39.0% (n=1,099), and other tx in 24.0% (n=677; antibody-drug conjugates and non-PBC). Among pts who received 1L PBC, 15.0% (n=157) initiated avelumab 1LM within 90 days of completing 1L PBC. Avelumab uptake in 2020-2023 by year was 10.8% (Jun-Dec 2020), 29.9%, 34.4%, and 24.8% (Jan-Aug 2023), respectively; 38.9% of pts were still receiving avelumab at the end of the study period. In the 1L PBC and IO cohorts, mean age (SD) was 65.5 (11.1) and 74.6 (10.7) years, respectively. 60% of pts were male. In the 1L PBC and 1L IO monotherapy cohorts, respectively, median follow-up (IQR) was 11.2 (5.6-20.3) and 8.6 (4.0-17.7) months (mo); median TTNT (IQR) was 4.8 (2.8-8.3) and 5.5 (2.8-11.0) mo; and median OS (95% CI) was 29.7 (25.1-37.2) and 20.0 (17.1-25.6) mo. In pts who received avelumab 1LM, median follow-up (IQR) from start of 1L PBC was 14.6 (9.2-21.3) mo; median TTNT (IQR) was 7.6 (6.2-12.3) mo; median time on avelumab tx was 5.0 (1.8-10.2) mo; and 1- and 2-year OS rates, respectively, from start of avelumab 1LM were 78% and 65%, and from start of 1L PBC were 84% and 68% (median OS was not estimable because >50% of pts remained alive at the end of the study period). Conclusions: Despite advances in 1L tx for mUC, IO monotherapy remains a prevailing option for older, commercially insured patients in the US. In this descriptive rw study, pts treated with 1L PBC had longer OS than pts treated with 1L IO monotherapy. Future studies with longer follow-up are needed to further evaluate pt outcomes.

Reevaluating the role of platinum-based chemotherapy in the evolving treatment landscape for patients with advanced urothelial carcinoma.

Platinum-based chemotherapy has been the standard first-line (1L) treatment for advanced urothelial carcinoma (UC) for decades, based on the proven efficacy and established safety profiles of cisplatin- and carboplatin-based regimens. With the emergence of novel regimens, it is important to reevaluate and contextualize the role of 1L platinum-based chemotherapy. Platinum-based chemotherapy followed by avelumab 1L maintenance in patients without disease progression following platinum-based chemotherapy was established as a standard 1L regimen based on the JAVELIN Bladder 100 phase III trial. More recently, the EV-302 phase III trial showed the superiority of 1L enfortumab vedotin (EV) + pembrolizumab versus platinum-based chemotherapy, and the Checkmate 901 phase III trial showed the superiority of 1L nivolumab + cisplatin/gemcitabine versus cisplatin/gemcitabine alone. These 2 regimens have now been included as standard 1L options in treatment guidelines for advanced UC. EV + pembrolizumab is now the preferred 1L treatment, and in locations where EV + pembrolizumab is not available or individual patients are not considered suitable, recommended options are platinum-based chemotherapy followed by avelumab maintenance or nivolumab + cisplatin-based chemotherapy. In this review, we discuss current treatment options for advanced UC recommended in guidelines, practical considerations with platinum-based chemotherapy, the role of avelumab 1L maintenance, recent phase III trials of EV + pembrolizumab and nivolumab + cisplatin/gemcitabine, safety profiles of recommended 1L treatments, and second-line treatment options.

Prescribers and patients drive maintenance therapy patterns in a community oncology practice: National guidelines versus the real-world experience

ObjectivePrevious studies have shown that first-line (1L) maintenance therapy (MT) with poly(ADP-ribose) polymerase inhibitors and/or bevacizumab improves outcomes among patients with advanced ovarian cancer (OC); however, these treatments are underutilized. This study aimed to provide a real-world understanding of MTs among patients with advanced OC who received 1L platinum-based chemotherapy (PBC). MethodsA retrospective chart review using iKnowMed electronic health records to identify patients aged ≥18 years with advanced OC who initiated 1L PBC between January 1, 2018–December 31, 2020. Following 1L PBC, patients could have received MT or active surveillance (AS). Kaplan–Meier methods were used to estimate time to treatment discontinuation (TTD), real-world progression-free survival (rwPFS), and overall survival (OS). ResultsOf the 600 chart-reviewed patients included, 239 (39.8 %) received MT and 315 (52.5 %) received AS. Patients who were <65 years of age, or those with higher-stage disease or those who had received neoadjuvant treatment, were more likely to initiate MT than AS. Genetic testing rates were low across both cohorts. Median (95 % confidence interval [CI]) TTD for the MT cohort was 13.6 months (11.0, 21.2). Median (95 % CI) rwPFS was 26.9 months (21.3, not reached) and 11.3 months (9.5, 13.0) for the 1L MT and AS cohorts, respectively (p < 0.0001). OS at 36 months was 82.4 % in the 1L MT cohort and 58.0 % in the 1L AS cohort. ConclusionsThis study reinforces clinical trial findings that 1L MT improves outcomes in patients with advanced OC; however, genetic testing rates and 1L MT remained low.

Avelumab first-line maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma: real-world results from a Korean expanded access program.

The JAVELIN Bladder 100 phase 3 trial demonstrated the efficacy and safety of avelumab administered as first-line (1L) maintenance treatment in patients with advanced urothelial carcinoma (UC) without disease progression after 1L platinum-based chemotherapy. This study provides the first real-world data from Korea regarding avelumab 1L maintenance treatment, comprising data obtained from a nationwide expanded access program (EAP). This open-label EAP was conducted at five centers from September 2021 until June 2023. Eligible patients had unresectable locally advanced or metastatic UC and were progression free after 1L platinum-based chemotherapy. Patients received avelumab 10 mg/kg intravenously every 2 weeks per local prescribing information. Safety and effectiveness were assessed by treating physicians according to routine practice. Overall, 30 patients were enrolled. At initial UC diagnosis, 20 patients (66.7%) had stage 4 disease and 12 (40.0%) had visceral metastases. The most common 1L chemotherapy regimen was gemcitabine + cisplatin (21 patients; 70.0%). All but one patient (96.7%) had received 4-6 cycles of 1L chemotherapy. The median interval from end of 1L chemotherapy to start of avelumab was 4.4 weeks. Median duration of avelumab treatment was 6.2 months (range, 0.9-20.7); nine patients (30.0%) received >12 months of treatment. Adverse events related to avelumab occurred in 21 patients (70.0%) and were grade ≥3 or classified as serious in three patients (10.0%). Median progression-free survival was 7.9 months (95% CI, 4.3-13.1). Overall survival was not analyzed because only one patient died. Results from this EAP demonstrated the clinical activity and acceptable safety of avelumab 1L maintenance treatment in Korean patients with advanced UC, consistent with previous studies.

Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from the JAVELIN Bladder 100 trial in patients (pts) with histological subtypes.

4567 Background: Results from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) led international treatment guidelines to recommend avelumab 1L maintenance as a standard-of-care treatment for pts with aUC without progression after 1L platinum-based chemotherapy (PBC). Around 20% of UCs are mixed with other histological subtypes/variants; these tumors do not have specific treatment guidelines and represent an unmet treatment need. In the large real-world AVENANCE study (NCT04822350; N=594) of avelumab 1L maintenance in pts with aUC in France, outcomes in pts with histological subtypes were consistent with those in the overall population. Here, we report a post hoc analysis of long-term outcomes from JAVELIN Bladder 100 in pts with predominantly UC mixed with &lt;50% histological subtype component. Methods: Eligible pts had unresectable locally advanced or metastatic UC without progression after 1L PBC and were randomized 1:1 to receive avelumab + best supportive care (BSC) or BSC alone. The primary endpoint was overall survival (OS) measured from randomization; secondary endpoints included progression-free survival (PFS) and safety. This post hoc analysis was conducted in all pts with histological subtypes. Results: In the avelumab + BSC and BSC alone arms, respectively, 44/350 and 57/350 pts had histological subtypes. At efficacy data cutoff (June 4, 2021), median follow-up in both arms was ≥38.0 mo. In pts with histological subtypes, OS and PFS measured from randomization were prolonged with avelumab + BSC vs BSC alone (Table). Long-term safety (cutoff, April 6, 2023) in treated pts with histological subtypes was generally consistent with the overall safety population. Treatment-related adverse events (TRAEs) of any grade occurred in 36 pts (83.7%) in the avelumab + BSC arm vs 1 pt (1.8%) in the BSC alone arm; grade ≥3 TRAEs occurred in 9 pts (20.9%) and 0 pts, respectively. Conclusions: This exploratory analysis shows the long-term efficacy and safety of avelumab 1L maintenance in pts with histological subtypes in JAVELIN Bladder 100. No new safety concerns were identified. These results were consistent with those in the overall population and support the use of avelumab 1L maintenance in pts with aUC without progression following 1L PBC, including pts with predominantly UC mixed with &lt;50% histological subtype component. Clinical trial information: NCT02603432 . [Table: see text]

Avelumab first-line maintenance (1LM) for advanced urothelial carcinoma (aUC): Long-term outcomes from JAVELIN Bladder 100 in patients (pts) with low tumor burden.

4566 Background: In the JAVELIN Bladder 100 phase 3 trial, avelumab 1LM + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in pts with aUC that had not progressed with 1L platinum-based chemotherapy (PBC). Results led to the incorporation of avelumab 1LM into international guidelines. Prior analyses have shown that low tumor burden (eg, nonvisceral metastases or lymph node [LN]-only disease) is associated with better outcomes in pts with aUC receiving immune checkpoint inhibitors. We report post hoc analyses of efficacy and safety in subsets of pts with low tumor burden from JAVELIN Bladder 100. Methods: Eligible pts with unresectable locally advanced (LA) or metastatic UC without progression after 1L PBC were randomized 1:1 to receive avelumab + BSC (n=350) or BSC alone (n=350). The primary endpoint was OS measured from randomization; secondary endpoints included PFS and safety. In this post hoc analysis, pts with nonvisceral metastases included those with LA disease or only nonvisceral disease, including bone metastasis, at randomization. Results: In the avelumab + BSC and BSC alone arms, 159 and 159 pts had nonvisceral metastases and 51 and 51 pts had LN-only disease, of whom 42 and 35 pts had LN-only disease in the pelvic/retroperitoneal area. At the efficacy data cutoff (June 4, 2021), median follow-up was ≥38 mo in both arms (≥2 y in all pts). In all subgroups, OS and PFS were prolonged with avelumab + BSC vs BSC alone (Table). Incidence of treatment-related adverse events (TRAEs) with avelumab were similar across subgroups. In the avelumab + BSC and BSC alone arms, subsequent anticancer drug treatment was received by 90 (56.6%) vs 119 pts (74.8%) with nonvisceral metastases, 27 (52.9%) vs 39 pts (76.5%) with LN-only disease, and 22 (52.4%) vs 27 pts (77.1%) with pelvic/retroperitoneal LN-only disease. Conclusions: Exploratory analyses suggest that avelumab 1LM has pronounced efficacy and manageable toxicity in pts with aUC who have low tumor burden, supporting its use as a standard of care in this setting. Clinical trial information: NCT02603432 . [Table: see text]

Real-world treatment patterns and outcomes in US patients (pts) with advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy (PBC) and anti–PD-(L)1 treatment.

8627 Background: Effective treatment options for advanced or metastatic NSCLC are limited, especially for pts who progress after treatment with PBC and an anti–programmed cell death 1 protein (PD-1) or ligand 1 (PD-L1) regimen. Examining real-world treatment patterns and long-term outcomes, we report on progression-free survival (PFS) and overall survival (OS) in pts with NSCLC who previously received PBC and anti–PD-(L)1 regimens. Methods: This study used the nationwide Flatiron Health electronic health record–derived deidentified database. Pts included in the analysis were ≥18 years old with an initial diagnosis of advanced or metastatic NSCLC and an ECOG PS of 0 or 1 who had received prior PBC and anti–PD-(L)1 therapy in 1 (in combination) or 2 (in sequence) lines and had initiated ≥1 subsequent line of treatment between 2018 and 2023; the start date of subsequent treatment (defined as the index regimen) was the index date. Pts were followed up until death or last available data through Mar 31, 2023. Pt characteristics, treatment patterns, and outcomes were analyzed for the overall pt group and according to initial treatment cohort (cohort 1: first-line [1L] PBC plus anti–PD-(L)1; cohort 2a: 1L PBC and second-line [2L] anti–PD-(L)1; or cohort 2b: 1L anti-PD-(L)1 and 2L PBC). PFS and OS were estimated using Kaplan-Meier methods. Results: Of 1793 pts, most were in cohort 1 (73.5%), with fewer pts in cohorts 2a (22.5%) and 2b (4.1%). The majority of pts in cohort 2b had PD-L1 ≥50% (n = 57, 78.1%), while the percentage was lower in cohorts 1 (n = 262, 19.9%) and 2a (n = 72, 17.9%). Most pts (n = 1626, 90.7%) had stage IV disease. Median time from advanced diagnosis to index date was 10.5 months (range, 1.1-103.8); median follow-up from index date was 7.8 months (range, 0.0-65.0). A broad range of treatments were used after PBC and anti–PD-(L)1 regimens; among all pts, the most common were docetaxel + ramucirumab and docetaxel monotherapy. Among all pts, median PFS and OS from the time of starting these index regimens were 5.29 and 11.20 months, respectively; PFS and OS were similar across cohorts. Conclusions: A broad range of subsequent treatments were used following PBC and anti–PD-(L)1 regimens, most commonly docetaxel with or without ramucirumab. Short median PFS and OS underscore a significant unmet need among pts previously treated with PBC and anti–PD-(L)1. [Table: see text]

Abstract A056: Development and application of an epithelial ovarian cancer-specific line of therapy algorithm using real-world data

Abstract Introduction. Characterizing lines of therapy (LoTs) helps researchers describe the epithelial ovarian cancer (EOC) patient treatment journey, but they are not routinely captured in real-world data. Algorithms must therefore be developed to transform individual treatment data into summary LoTs. Special considerations must be made for EOC as maintenance (MTx) therapy, which includes poly ADP ribose polymerase inhibitors (PARPi) and/or bevacizumab, may be given following treatment (Tx) lines. We developed an EOC-specific LoT algorithm and evaluated its performance using real-world data. Methods. Patients were sampled from the Syapse Learning Health Network, a database of cancer patients treated in large community health systems across 25 states in the US and were eligible for inclusion if they were diagnosed with EOC between 01/01/2015 and 09/30/2022 (index date) and had manually curated systemic therapy data. All patients were followed through 12/31/2022. Assignment of Tx and MTx lines and regimens and allowable treatment gaps were based on national treatment guidelines and typical disease course. To distinguish between Tx and MTx lines, all eligible patients who received systemic therapy following the initial diagnosis of EOC were assigned first-line (1L) Tx, and each subsequent LoT was classified as a Tx or MTx line depending on the therapies in the present LoT and one immediately preceding it. Therapies could be added or switched within a LoT, and assigned regimens distinguished between therapies given in combination from switch therapies. A shorter treatment gap was used to identify later LoTs to account for more rapid disease progression. Unexpected regimens were flagged for further evaluation. A subset of patients with advanced stage, non-mucinous EOC who received 1L platinum-based chemotherapy were manually reviewed by a medical oncologist to identify patients who received 1L MTx. Results. There were 2,275 eligible EOC patients. 415 patients with missing, incomplete, or invalid therapy dates were excluded, leaving 1,860 patients in the LoT analysis. Median follow-up was 23 months (IQR, 13-41 months). Nearly half (48%) of the patients received only one LoT; 15% of patients received 3 or more LoTs. Out of all patients, 15% received 1L MTx without any subsequent treatment. The top 1L Tx regimens were platinum and taxane combination, platinum and taxane plus bevacizumab, and platinum alone (73%, 16%, and 2% of patients who received 1L Tx, respectively). The top 1L MTx regimen was PARPi alone, followed by bevacizumab alone and bevacizumab plus PARPi (57%, 35%, and 8% of patients who received 1L MTx, respectively). 1,355 (74%) patients were identified for expert review. Among these, concordance in 1L MTx determination between expert review and the algorithm was 98%. Conclusion. The EOC-specific LoT algorithm performed well: line and regimen distributions aligned with real-world practice and expert clinical review. Researchers may wish to utilize this algorithm for real-world studies of ovarian cancer. Citation Format: Connor Sweetnam, Tirza Areli Calderón Boyle, Sara Burns, Jessica Perhanidis, Matthew Rioth, Rayna K Matsuno. Development and application of an epithelial ovarian cancer-specific line of therapy algorithm using real-world data [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A056.

Germline mutations of homologous recombination genes and clinical outcomes in pancreatic cancer: a multicenter study in Taiwan

BackgroundCancer susceptibility germline mutations are associated with pancreatic ductal adenocarcinoma (PDAC). However, the hereditary status of PDAC and its impact on survival is largely unknown in the Asian population.MethodsExome sequencing was performed on 527 blood samples from PDAC individuals and analyzed for mutations in 80 oncogenic genes. Pathogenic and likely pathogenic (P/LP) germline variants were diagnosed according to the ACMG variant classification categories. The association between germline homologous recombination gene mutations (gHRmut, including BAP1, BRCA1, BRCA2, PALB2, ATM, BLM, BRIP1, CHEK2, NBN, MUTYH, FANCA and FANCC) and the treatment outcomes was explored in patients with stage III/IV diseases treated with first-line (1L) platinum-based versus platinum-free chemotherapy.ResultsOverall, 104 of 527 (19.7%) patients carried germline P/LP variants. The most common mutated genes were BRCA2 (3.60%), followed by ATR (2.66%) and ATM (1.9%). After a median follow-up duration of 38.3-months (95% confidence interval, 95% CI 35.0–43.7), the median overall survival (OS) was not significantly different among patients with gHRmut, non-HR germline mutations, or no mutation (P = 0.43). Among the 320 patients with stage III/IV disease who received 1L combination chemotherapy, 32 (10%) had gHRmut. Of them, patients receiving 1L platinum-based chemotherapy exhibited a significantly longer median OS compared to those with platinum-free chemotherapy, 26.1 months (95% CI 12.7–33.7) versus 9.6 months (95% CI 5.9–17.6), P = 0.001. However, the median OS of patients without gHRmut was 14.5 months (95% CI 13.2–16.9) and 12.6 months (95% CI 10.8–14.7) for patients receiving 1L platinum-based and platinum-free chemotherapy, respectively (P = 0.22). These results were consistent after adjusting for potential confounding factors including age, tumor stage, performance status, and baseline CA 19.9 in the multivariate Cox regression analysis.ConclusionsOur study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHRmut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis.

Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (aUC): Long-term outcomes from the JAVELIN Bladder 100 trial in patients (pts) with high body mass index (BMI).

600 Background: Avelumab 1L maintenance is recommended as standard of care by international treatment guidelines for pts with aUC that has not progressed with 1L platinum-based chemotherapy, based on level 1 evidence from the phase 3 JAVELIN Bladder 100 trial (NCT02603432). In the trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone (median OS, 23.8 vs 15.0 mo; HR, 0.76 [95% CI, 0.63-0.91]; 2-sided p=0.0036). The long-term safety of avelumab 1L maintenance was also demonstrated. It is estimated that 25% of the world’s population will have BMI ≥30 by 2035, and high BMI is a risk factor for bladder cancer. We report post hoc analyses of long-term outcomes from JAVELIN Bladder 100 in pts with high BMI (≥30) at baseline. Methods: Eligible pts with unresectable locally advanced or metastatic UC without progression after 4-6 cycles of 1L platinum-based chemotherapy were randomized 1:1 to receive avelumab 10 mg/kg every 2 wk + BSC (n=350) or BSC alone (n=350). The primary endpoint was OS; secondary endpoints included PFS and safety. Results: At data cutoff (June 4, 2021), median follow-up was ≥38 mo in both arms. In the avelumab + BSC and BSC alone arms, 67 and 55 pts had high BMI at baseline, respectively. In these pts, median OS was 20.8 mo (95% CI, 16.9-34.4) with avelumab + BSC vs 12.7 mo (95% CI, 8.1-26.6) with BSC alone (HR, 0.77 [95% CI, 0.49-1.21]); 2-y OS rates were 47.8% vs 37.6%, respectively. Median PFS by investigator was 5.6 mo (95% CI, 3.7-7.5) with avelumab + BSC vs 2.1 mo (95% CI, 1.9-4.0) with BSC alone (HR, 0.64 [95% CI, 0.42-0.97]); 2-y PFS rates were 23.5% vs 11.3%, respectively. Long-term safety in pts with high BMI was generally consistent with the overall safety population (Table). Conclusions: This exploratory analysis shows the long-term efficacy and tolerability of avelumab 1L maintenance in pts with high BMI in JAVELIN Bladder 100, with no new safety concerns identified. These results further support the use of avelumab 1L maintenance as standard of care in pts with aUC who are progression free after 1L platinum-based chemotherapy, including pts with high BMI. Clinical trial information: NCT02603432 . [Table: see text]

Real-world (rw) treatment patterns, sequencing, and outcomes in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) receiving avelumab first-line maintenance (1LM) in the US.

605 Background: Avelumab 1LM is recommended in international guidelines for pts with la/mUC and disease control after 1L platinum-based chemotherapy (PBC). This study describes the treatment landscape after FDA approval of avelumab in June 2020 by examining pt characteristics, treatment patterns and sequencing, and rw outcomes in pts treated with avelumab 1LM. Methods: This noninterventional retrospective study identified pts with la/mUC who received avelumab 1LM in the US using data from Flatiron Health’s electronic health record database. Pts aged ≥18 y with ≥2 visits on/after Jan 1, 2011, diagnosed with la/mUC from Jan 1, 2019 - Dec 31, 2022, treated with 1L PBC followed by avelumab 1LM on/after Jul 1, 2020, ≤90 d after 1L PBC discontinuation, and with no disease progression ≤14 wk after 1L PBC were included. Treatment patterns in 1LM, second line (2L), and third line (3L) were assessed. Clinical outcomes, including rw progression-free survival (rwPFS), rw overall survival (rwOS), time to treatment discontinuation (TTD), and time to next treatment (TTNT) from 1LM or 2L initiation, were assessed using Kaplan-Meier methods. Results: 214 avelumab 1LM-treated pts met eligibility criteria. Median age was 70 y; most pts were male (77%), White (66%), and had an ECOG of 0-1 (77%). Median follow-up from 1LM was 8.7 mo. Of 96 (45%) pts who received 2L treatment post avelumab 1LM, enfortumab vedotin (EV) monotherapy (55%) was most common, followed by carboplatin-based therapy (11%). Of 40 (42%) pts who received 3L treatment, EV monotherapy was most common (25%), followed by sacituzumab govitecan (20%). Median PFS and OS from start of avelumab 1LM was 5.1 (95% CI 4.1-7.0) and 23.8 (95% CI 18.2-NE) mo. Median TTNT from avelumab 1LM initiation was 7.0 (95% CI 5.6-8.6) mo. Of pts who received 2L EV, median rwPFS and rwOS from 2L initiation were 4.9 (95% CI 3.9-8.8) and 11.2 (95% CI 6.8-NE) mo. Further rw outcomes are presented in the Table. Conclusions: Clinical outcomes in this study are aligned with those of the JAVELIN Bladder 100 trial (NCT02603432), further supporting avelumab 1LM as a standard of care. With each additional line of therapy, substantial treatment attrition and less favorable clinical outcomes were observed. This study provides insights into the sequencing of treatments and management of pts with la/mUC after disease progression with avelumab 1LM in this rapidly evolving therapeutic landscape. The use of more effective upfront therapies may decrease the attrition rates. [Table: see text]

Subgroup analyses from READY: Real-world data from an Italian compassionate use program (CUP) of avelumab first-line maintenance (1LM) treatment for locally advanced or metastatic urothelial carcinoma (la/mUC).

558 Background: A multicenter CUP provided early access to avelumab 1LM in Italian patients (pts) with Ia/mUC before reimbursement. Real-world pt characteristics and outcomes with avelumab 1LM from READY were reported previously. Here, we report updated data and subgroup analyses of effectiveness with avelumab 1LM. Methods: This prospective, noninterventional CUP included pts with la/mUC who were progression free after 1L platinum-based chemotherapy (PBC; 4-6 cycles, starting avelumab 1LM 4-10 wk after last PBC dose). Pts were enrolled from Jan 18, 2021 to Mar 7, 2022. Avelumab was provided per physician request and after approval by local ethics committees, per Italian compassionate-use regulations. Pts who had a relapse within 12 mo of prior adjuvant or neoadjuvant systemic therapy, including immune checkpoint inhibitors, were excluded. Results: 464 pts were included (78.45/21.55% male/female; median age, 70.0 y [interquartile range, 63.0-76.0]). At data cutoff (July 30, 2023), median follow-up from start of avelumab 1LM in 411 evaluable pts was 20.24 mo (95% CI, 19.78-20.93); median overall survival (OS) and progression-free survival (PFS) from start of avelumab were 26.22 mo (95% CI, 19.97-not estimable [NE]) and 7.63 mo (95% CI, 5.79-9.24), respectively. In pts aged &lt;60 y (n=53), 60-70 y (n=150), and &gt;70 y (n=208), median OS (95% CI) was not reached (NR; 12.86 mo-NE), NR (24.21 mo-NE), and 24.01 mo (16.94-NE), and median PFS was 5.20 mo (2.83-6.71), 7.70 mo (5.26-10.07), and 8.82 mo (6.05-12.93), respectively. In pts who received 1L cisplatin + gemcitabine (n=183) and 1L carboplatin + gemcitabine (n=219), median OS (95% CI) was NR (16.05 mo-NE) and 25.10 mo (19.97-NE), and median PFS was 6.61 mo (5.30-9.18) and 8.42 mo (6.05-12.73), respectively. The table shows OS and PFS in other subgroups defined by best response to 1L PBC and number of 1L PBC cycles received. Conclusions: Real-world outcomes with avelumab 1LM in this CUP in Italy show clinical benefit across various subgroups. These data are clinically relevant and are consistent with other real-world country-based studies and the phase 3 JAVELIN Bladder 100 trial. Findings further support the use of avelumab 1LM as standard of care in pts with la/mUC who are progression free after PBC. [Table: see text]

Avelumab first-line maintenance (1LM) in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC) in the Czech Republic: Interim real-world results from a national reimbursement registry.

557 Background: Avelumab 1LM treatment is recommended by international guidelines as the standard of care for pts with la/mUC that has not progressed with 1L platinum-based chemotherapy (PBC) and has been approved in the EU since Jan 2021. In the Czech Republic, following EU approval, there is a requirement to provide real-world data for “highly innovative medicinal products” such as avelumab 1LM when reimbursement decisions are temporary. Obtaining reimbursement therefore requires the creation of a registry to collect real-world data. We report interim results from a retrospective analysis of a national reimbursement registry for avelumab 1LM in the Czech Republic. Methods: Registry data were collected by the Office of Health Insurance (KZP) for pts with la/mUC receiving avelumab 1LM in the Czech Republic between Oct 2021 and Jan 2023. The primary endpoint was overall survival (OS) from the start of avelumab 1LM (index date); secondary endpoints included progression-free survival (PFS) from the start of avelumab 1LM and safety. Descriptive statistics were used to analyze the data. OS and PFS were estimated using the Kaplan-Meier method. Results: 59 eligible pts with la/mUC were treated and documented. At data cutoff (Jan 3, 2023), median follow-up was 6.1 mo (range, 0-16.5). All pts were White; 43 were male and 16 were female. At the start of avelumab 1LM, median age was 71 y (range, 49-84) and 22 pts (37.3%) had visceral metastases. 1L PBC was cisplatin-based in 30 pts (50.8%), carboplatin-based in 24 (40.7%), and both (switched from cisplatin to carboplatin) in 5 (8.5%). Best response to 1L PBC was complete response in 5 pts (8.5%), partial response in 30 (50.8%), and stable disease in 24 (40.7%). Median time from the end of PBC to the start of avelumab was 4.1 wk (range, 1.0-44.0). Effectiveness data for avelumab 1LM are shown in the Table. OS and PFS data are immature, with only 14 pts (23.7%) having died or had disease progression at the time of analysis. 10 adverse events were reported in 9 pts (15.3%), including grade 3 infusion-related reaction (1 pt), grade 2 diarrhea (2 pts), and grade 2 nephritis, pneumonitis, and Addison disease (1 pt each). At last evaluation, 53 pts were alive, of whom 5 pts had started subsequent treatment. Conclusions: This is the first study of pts with la/mUC treated with avelumab 1LM in a real-world setting in the Czech Republic. These preliminary data agree with the results of the phase 3 JAVELIN Bladder 100 trial and other real-world studies, confirming the effectiveness and manageable safety profile of avelumab 1LM in la/mUC. Follow-up for OS is ongoing. [Table: see text]

Early recurrence, time-to-recurrence, and recurrence patterns: Assessing their impact on survival outcomes in head and neck squamous cell carcinoma (R/M-HNSCC) patients treated with first line platinum-based chemotherapy.

R/M-HNSCC patients typically receive 1L platinum-based chemotherapy with pembrolizumab or cetuximab. However, the outcomes for patients with early recurrence (<6 months) remain unclear due to their exclusion from most 1L studies. This study aimed to assess the impact of time-to-recurrence intervals (TTRI) and recurrence patterns on the survival of R/M-HNSCC patients. We identified non-curable R/M-HNSCC patients at our institution from 1/2008 through 6/2020. We analyzed the outcomes of early recurrent patients who received 1L systemic treatment, with different TTRIs and recurrence patterns. Our study included 234 eligible patients. The majority (47%) experienced early recurrence (<6 months), while 22%, 20%, and 11% had recurrences at 6-12 months, >12 months, and de novo metastasis, respectively. The platinum-based regimen was the most commonly used chemotherapy (86%), with cetuximab and immunotherapy utilized in 3% and 5% of cases, respectively. Significant differences in PFS and OS were observed among TTRI groups. For patients with early recurrence, both platinum-doublet and monotherapy treatments significantly improved OS. Locoregional recurrence (47%) was the most common, followed by distant metastasis (22%) and both (20%). Recurrence patterns were significantly associated with OS but not with PFS. In multivariate analysis, TTRI ≥12 months significantly correlated with improved PFS (HR 0.51; p = 0.004) and OS (HR 0.58; p = 0.009), whereas recurrent pattern did not. TTRI significantly influenced the survival, while recurrence patterns did not. In our study, the retrospective design limited our ability to definitively establish whether early recurrent R/M-HNSCC patients would benefit more from platinum-doublet. Despite poor prognosis, early recurrent patients benefited from 1L systemic treatments. Given the variation in prognoses, TTRI should be considered a stratification factor in future clinical trials.

First-line maintenance use among patients with advanced ovarian cancer in a community oncology setting: A retrospective observational study in the United States (US).

544 Background: Ovarian cancer (OC) accounts for 1.1% of all cancers and is the fifth leading cause of cancer-related death in women in the US. Poly(ADP-ribose) polymerase inhibitors (PARPi) are targeted therapies that induce synthetic lethality in tumor cells with homologous recombination deficiencies, including BReast CAncer gene (BRCA) mutations. Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF) ligand to inhibit angiogenesis. Active surveillance (AS) is close monitoring of patients with OC without providing treatment. Both maintenance therapy and AS require frequent surveillance to achieve optimal outcomes. Previous studies have shown that maintenance therapy with PARPi and/or bevacizumab are effective treatment strategies for patients with advanced stage OC, however, they are often underutilized by physicians (Gogineni V et al. J Cancer 2021;12(1):38-53). Methods: This retrospective study accessed the Ontada iKnowMed database to review the charts of patients who initiated platinum-based chemotherapy (PBC) in the first-line (1L) setting between January 1, 2018–December 31, 2020. Follow-up data for patients were collected through September 30, 2021. Kaplan-Meier estimates were used to compare utilization of maintenance therapy versus AS following 1L PBC for real-world progression-free survival (rwPFS) and overall survival (OS). Results: Following 1L PBC, 239 (39.8%) patients received maintenance therapy (56.5% received PARPis, 34.3% received bevacizumab and 9.2% received PARPi and bevacizumab) and 315 (52.5%) received AS. Median (min, max) follow-up time from initial diagnosis was 20.1 (2.2, 43.3) months for patients who received AS and 20.0 (4.4, 44.2) months for patients who received 1L maintenance therapy. Mean (standard deviation [SD]) age was 62.4 (12.0) and 65.8 (12.9) years for the maintenance and AS groups, respectively. Biomarker testing was not available in &gt;40% of patients. Observed median rwPFS was 26.9 months (95% confidence interval [CI]: 21.3, not reached) for patients who received 1L maintenance therapy and 11.3 months (95% CI: 9.5, 13.0) for patients who received AS (log rank p&lt;0.0001). Whilst observed median OS was not reached for either group, OS probabilities were 95.7%, 88.3%, and 82.4% at 1 year, 2 years, and 3 years respectively for patients who received 1L maintenance therapy and 85.9%, 71.5%, and 58.0% for patients who received AS. Conclusions: Despite previous studies demonstrating the benefits of maintenance therapy, &lt;50% of patients in this study received 1L maintenance therapy following 1L PBC. These results show that maintenance therapies can improve rwPFS and OS in patients with advanced OC compared to AS. Therefore, there is a need to better understand maintenance therapy provider preferences and/or challenges. Funding: GSK 217225.

Real-world (RW) use of niraparib (Nir) monotherapy (mono) as first-line (1L) switch maintenance (1LSM) therapy following chemotherapy (CT) plus bevacizumab (bev) induction treatment in patients (pts) with epithelial ovarian cancer (EOC) in the SW1TCH study.

536 Background: In the RW CHAR1ZMA study, 414 pts with EOC treated with 1L platinum-based CT (pbCT) and receiving 1L maintenance (1LM) nir mono had a median time to next treatment (TTNT) from end of 1L, a proxy for RW progression-free survival, of 13.3 mo (95% CI, 12.0–15.8 mo).1 Limited data exist on RW outcomes in pts with EOC who receive nir mono as 1LSM after 1L pbCT + bev treatment. The SW1TCH study describes nir mono use and outcomes as 1LSM therapy after 1L pbCT + bev treatment in a US RW setting. Methods: Using the nationwide Flatiron Health electronic health record–derived deidentified database, this retrospective observational study included pts ≥18 y of age at initial EOC diagnosis who received 1L pbCT + bev treatment followed by nir 1LM mono, initiated between Jan 1, 2017, and Sep 2, 2022. The index date was the initiation of nir 1LM. Pts were followed until the earliest of date of death, last activity, or end of study (Nov 30, 2022). Time to treatment discontinuation (TTD) and TTNT were estimated with Kaplan-Meier methods. Results: Of 93 pts selected, median age at index was 67 y (IQR, 60–72 y). Most pts had an Eastern Cooperative Oncology Group performance score of 0–1 (75.3%) and stage III/IV disease at diagnosis (89.2%). Overall, 86.0% of pts had BRCA wild-type EOC. 19.4% and 22.6% of pts had evidence of homologous recombination (HR)-deficient and HR-proficient EOC, respectively, whereas HR deficiency status was unknown for 58.1%. Median duration of 1L therapy was 4.8 mo (IQR, 3.6–6.0 mo), and median time from end of 1L pbCT to start of 1LM was 1.2 mo (IQR, 0.8–1.8 mo). Reasons for nir discontinuation are shown in the Table. Median TTD from index was 9.3 mo (95% CI, 6.0–11.3 mo). Median TTNT from end of 1L was 12.9 mo (95% CI, 11.5–19.0 mo). Conclusions: Observed results are consistent with CHAR1ZMA,1 suggesting the RW benefit of nir mono in 1LM regardless of bev use with1L pbCT. This RW study demonstrates that nir mono as 1LSM therapy is a viable treatment option for pts with advanced EOC.

Healthcare costs associated with first-line (1L) treatment of patients with locally advanced or metastatic urothelial carcinoma (la/mUC) in the United States (US).

11 Background: In 2023 in the US, 82,290 new cases of bladder cancer and 16,670 related deaths were estimated. Prior analyses assessing the economic burden of la/mUC in the current and evolving treatment landscape have been limited. This study aimed to estimate the direct medical costs of treating patients with la/mUC, from US Medicare and commercial perspectives. Methods: A cost model was developed to estimate annual direct medical care costs in patients with la/mUC eligible for 1L platinum-based chemotherapy (PBC) in 2023. Costs (2023 USD)—including drug acquisition and administration, disease management and adverse event (AE) management—were calculated, including subsequent therapy costs. Inputs included estimated number of treated patients per year, treatment duration, progression-free survival and overall survival with various therapies, AEs incidence, and market shares. Efficacy and safety data were sourced from product prescribing information, epidemiology data from Surveillance, Epidemiology, and End Results (SEER) database and published literature. Market share assumptions were based on market research data. Results: For a hypothetical health plan with 1,000,000 members, 108 and 22 patients with la/mUC from Medicare and commercial perspectives, respectively, were estimated to be eligible for 1L PBC in 2023. Estimated total annual costs per treated patient are shown in the Table below. With market share data comprising 1L PBC, with and without avelumab (AVE) 1L maintenance (61% and 25%) and enfortumab vedotin (EV) + pembrolizumab (PEM) (for cisplatin-ineligible patients, 14%), annual costs of $16,673,645 ($12,861 per treated member per month) and $4,637,226 ($17,852 per treated member per month) were estimated for Medicare and commercial perspectives, respectively. Drug acquisition costs in 1L represented most of the total costs (Medicare, 75%; commercial, 64%). Conclusions: Understanding the economic burden associated with la/mUC treatments may facilitate informed decision making on treatment choice and optimal sequencing. Further real-world studies are needed to assess the impact of these innovative treatments on disease and AE management costs of la/mUC. [Table: see text]

Evaluating Oncologists' Practice Patterns and Decision-Making in Locally Advanced or Metastatic Urothelial Carcinoma: The US Physician PARADIGM Study.

The treatment landscape for locally advanced/metastatic urothelial carcinoma (la/mUC) has evolved. This study examined US prescribing patterns and clinical decision-making for first-line (1L) and first-line maintenance (1LM) treatment. US-based oncologists (N = 150) completed an online survey on patient demographics, practice patterns, and important factors considered in 1L/1LM selection. Multivariable logistic regression was used to assess factors associated with more vs less frequent 1L/1LM prescribing. Physician reports estimated that 23% of patients with la/mUC had not received any systemic therapy in the previous 6 months; however, 46% received 1L, 32% received second-line, and 22% received subsequent-line systemic treatments. Of patients who were receiving 1L treatment, 72% were estimated to be receiving 1L platinum-based chemotherapy. Around 69% of patients eligible for 1LM received the treatment. Physicians categorized as frequent prescribers reported overall survival (OS), disease control rate (DCR), and rate of grade 3/4 adverse events (AEs) as factors associated with 1L treatment selection (all P < .05). OS, rate of grade 3/4 immune-mediated AEs, and inclusion in institutional guidelines were reported as attributes used in 1LM treatment selection (all P < .05). Multivariable analysis revealed OS, DCR, and rate of grade 3/4 AEs as important factors in oncologists' 1L treatment selection; academic practice setting and use of Response Evaluation Criteria in Solid Tumors version 1.1 were associated with 1LM use (all P < .05). OS and AEs were found to be relevant factors associated with offering 1L and 1LM treatment. Variability exists in physicians' decision-making in the real-world setting for la/mUC.

Characteristics, treatment patterns, and clinical outcomes in patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertions.

Epidermal growth factor receptor (EGFR) exon 20 insertions (ex20ins) are associated with poor prognosis and resistance to traditional therapies in patients with non-small cell lung cancer (NSCLC). We aimed to elucidate the characteristics and treatment patterns to improve outcomes among this population in Taiwan. Patients with advanced or recurrent NSCLC harboring EGFR ex20ins from 2011 to 2021 were reviewed. The treatment groups were classified as platinum-based chemotherapy (PtC), EGFR tyrosine kinase inhibitor (TKI), and others. The response to therapy, objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and factors associated with survival were analyzed. Among the 71 patients, most were never-smoking males with stage IVB adenocarcinoma. The most common first-line (1L) regimen was PtC, followed by TKI. The most common second-line (2L) regimen was TKI. The median PFS of 1L treatment was 5.03 months, and the median OS was 18.43 months. Compared with that of TKI, 1L PtC use was associated with a higher ORR (26.3% vs. 9.1%) and DCR (60.5% vs. 18.2%) and a longer PFS (5.37 vs. 3.13 months, p = 0.044). PFS was also significantly longer in the 2L PtC group than in the 2L TKI group (4.73 vs. 2.25 months, p = 0.047). No patients receiving an immune checkpoint inhibitor-based regimen exhibited a therapeutic response. This study demonstrated the heterogeneous clinical characteristics and treatment pattern of NSCLC patients with EGFR ex20ins, underscoring the need for more effective therapies for this distinct molecular subtype.