bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of the PI3Kδ inhibitor zandelisib (ME-401) on an intermittent schedule (IS) in patients with relapsed/refractory follicular lymphoma (FL) with progression of disease within 24 months of first-line chemoimmunotherapy (POD24).
Authors: Pagel John M. , Reddy Nishitha , Jagadeesh Deepa , Stathis Anastasios , Asch Adam Steven , Salman Huda S. , Kenkre Vaishalee Padgaonkar , Soumerai Jacob Drobnyk , Llorin-Sangalang Judith , Gorbatchevsky Igor , Li Joanne , Zelenetz Andrew David 
Published: June 2021

7550 Background: FL patients (pts) with POD24 have poorer survival and may benefit from novel therapies at relapse. Zandelisib, a potent, selective, and structurally differentiated oral PI3kδ inhibitor was evaluated in a dose escalation/expansion Phase 1b study for FL demonstrating a high objective response rate (ORR) and well tolerated when given on IS (J Clin Oncol 2020;38:#8016). We report here results based on POD24 status (NCT02914938). Methods: Eligible pts had ≥1 prior therapy, adequate bone marrow and organ function, ECOG performance status ≤2, and no prior PI3K therapy. Zandelisib was administered at 60 mg once daily for 8 weeks followed by IS on days 1-7 of each subsequent 28-day cycle, either as monotherapy or with rituximab at 375 mg/m2 for 8 doses in Cycles 1-6. Treatment was continued until disease progression, intolerance, or withdrawal of consent. Imaging scans were obtained after 2 and 6 cycles, and then every 6 cycles. Response was reported based on Lugano criteria. Results: 37 FL pts were enrolled and received zandelisib on IS as monotherapy (N = 18) or in combination with rituximab (N = 19). Median number of prior therapies = 2 (range, 1-5). The ORR was 86.5% (32/37) with 27% CR (complete response). In the monotherapy group the ORR and CR were 77.8 % (14/18) and 27.8% and with rituximab 94.7% (18/19) and 26.3% respectively. Median duration of response (DOR) among all pts was not reached with a median follow-up of 16.9 months (mos) (1.2-33.1+). 22 pts (59%) were POD24, of which 15 (68%) had ≥2 prior lines of therapy. Despite more refractory disease, ORR among the POD24 pts was 81.8% (Table). Zandelisib on IS was well tolerated. 3 pts (8%) discontinued therapy due to an adverse event (AE) for any cause. Grade (Gr) 3 AE of special interest (AESI) were 2 (5.4%) diarrhea, 2 (5.4%) colitis, 3 (8.1%) rash, 3 (8.1%) ALT elevation, 1 (2.7%) AST elevation and no pulmonary infection. Conclusions: Zandelisib administered on IS as monotherapy or with rituximab resulted in a high-rate of durable responses in FL, both in POD24 and non-POD24 groups and therapy was well-tolerated with low rate of Gr 3 class-related AESI and discontinuation rate due to AE’s. Zandelisib as monotherapy is being evaluated in a global Phase 2 study in FL and MZL after failure of 2 prior therapies (NCT03768505). A Phase 3 study of zandelisib plus rituximab in FL and MZL after failure of prior immunochemotherapy will begin enrollment in 2021. Clinical trial information: NCT02914938. [Table: see text]
Long-term follow-up results of a phase II study of dose-adjusted (DA)-EPOCH-R with high-dose methotrexate (HD-MTX) for newly diagnosed stage II-IV CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL).
Authors: Miyazaki Kana , Sakai Rika , Iwaki Noriko , Yamamoto Go , Yamada Tomomi , Nishimura Yuki , Tamaru Satoshi , Asano Naoko , Miyawaki Kohta , Izutsu Koji , Kinoshita Tomohiro , Suzuki Ritsuro , Ohshima Koichi , Kato Koji , Katayama Naoyuki , Yamaguchi Motoko 
Published: June 2021

7551 Background: CD5+ DLBCL is characterized by a poor prognosis and frequent central nervous system (CNS) relapse after standard immunochemotherapy. In the primary analysis of our multicenter phase II study of DA-EPOCH-R/HD-MTX for newly diagnosed stage II-IV CD5+ DLBCL, the 2-year (yr) progression-free survival (PFS) was 79% and the 2-yr CNS relapse rate was 9% at a median follow-up of 3.1 yrs (Miyazaki, et al. 2020). The aim of this preplanned 5-yr follow-up was to assess PFS, overall survival (OS), the CNS relapse rate, and late toxicity. Methods: A total of 47 patients (pts) with newly diagnosed stage II-IV CD5+ DLBCL between 20-75 yrs old and ECOG PS of 0-3 were enrolled. The treatment included 4 cycles of DA-EPOCH-R followed by 2 cycles of HD-MTX (3.5 g/m2) and 4 additional cycles of DA-EPOCH-R. Intrathecal administration of MTX and/or cytarabine was not allowed. 45 (96%) pts completed the protocol treatment. The data were updated as of December 1, 2020. Results: The median follow-up of alive pts was 6.0 yrs (range, 5.0-7.7). The pts’ characteristics were as follows: age, 37-74 yrs (median, 62); male, 38%; ECOG PS > 1, 4%; stage III/IV, 57%; IPI HI/H, 47%; CNS-IPI high, 21%; and ABC/GCB/unclassified (n = 46), 85%/9%/7%. The 5-yr PFS and OS were 72% (95% CI, 57-83%) and 79% (95% CI, 64-88%), respectively. The 5-yr PFS and OS of pts with CD5+ ABC DLBCL (n = 39) were 72% and 74%, respectively. The 5-yr CNS relapse rate in all 47 pts was 9% (95% CI, 3-22%). There were no CNS relapse events after the primary analysis. Neither grade 3/4 late adverse events nor cardiac events of any grade were observed. Possible second malignancies were recorded in 6 (13%) pts. Among them, one pt who received R-ICE as salvage therapy experienced acute myeloid leukemia. The other 2 pts had colon cancers treated with endoscopic polypectomy/mucosal resection. Conclusions: Both the survival benefit and safety of DA-EPOCH-R/HD-MTX were maintained during a 5-yr follow-up, indicating the excellent efficacy, and safety of this approach as a first-line therapy for CD5+ DLBCL. Clinical trial information: UMIN000008507.
Surgical outcomes for early-stage non-small cell lung cancer at facilities with stereotactic body radiation therapy programs.
Authors: Syed Yusef , Stokes William A. , Khullar Onkar , Sebastian Nikhil , Rupji Manali , Yuan Liu , Bradley Jeffrey D. , Higgins Kristin Ann , Curran Walter J , Ramalingam Suresh S. , Sancheti Manu , Fernandez Felix , Moghanaki Drew 
Published: June 2021

8538 Background: Patients undergoing surgery for early-stage non-small cell lung cancer (NSCLC) may be at high-risk for post-operative mortality. Access to stereotactic body radiation therapy (SBRT) offers a less invasive alternative for this population that may facilitate more appropriate patient selection for surgery. Methods: An analysis of all patients with early-stage NSCLC reported to the National Cancer Database between 2004-2015 was performed. Post-operative mortality rates were derived using vital status data. Utilization of SBRT was defined by each facility’s SBRT Experience in years and SBRT-to-Surgery volume ratios, defined by quartiles. Multivariable logistic regression with backward elimination was used to test for independence of associations between exposures of interest and post-operative mortality. Interaction testing was performed to assess the statistical relationship of covariates found to have independent associations. Results: The study cohort consisted of 202,542 patients who underwent surgical resection of clinical stage T1-T2 NSCLC (AJCC 7th edition). The 90-day post-operative mortality rate declined significantly during the study period from 4.6% to 2.6% (p < 0.001). During this period, the proportion of facilities that utilized SBRT increased from 3.3% to 77.5% (p < 0.001) and the proportion of patients treated with SBRT increased significantly from 0.7% to 15.4% (p < 0.001). Lower 90-day post-operative mortality rates were observed at facilities with greater than six years of SBRT experience (OR 0.84, CI 0.76-0.94, p = 0.003) and SBRT-to-Surgery volume ratios above 17% (OR 0.85, CI 0.79-0.92, p < 0.001). Additional covariates associated with 90-day mortality included higher surgical volume, geographic region, year of diagnosis, age, sex, race, insurance status, facility type, Charlson-Deyo score, clinical T stage, histology, anatomic location, surgery type, and prior malignancy. Interaction testing between these covariates was negative, demonstrating that higher SBRT Experience and SBRT-to-Surgery volume ratios were independently associated with lower 90-day surgical mortality. Conclusions: Patients who underwent surgery for early-stage NSCLC at facilities with higher SBRT Experience and SBRT-to-Surgery volume ratios had lower rates of post-operative mortality. These findings suggest that the availability of SBRT may be a surrogate for a more comprehensive and safer approach to matching patients to surgery or SBRT. The observation of higher post-operative mortality rates at facilities without an SBRT program deserves further study.
A comparative analysis of mortality between black and white stage III non–small cell lung cancer patients in the United States.
Authors: Elimimian Elizabeth Blessing , Arteta-Bulos Rafael , Liang Hong , Bilani Nadeem , Elson Leah , Saravia Diana , Alley Evan W. 
Published: June 2021

8552 Background: Lung cancer remains the leading cause of cancer death in the United States (U.S.). For stage III non-small cell lung cancer (NSCLC), concurrent chemotherapy (CT) plus radiotherapy (RT) within 30 days (CCRT) confers a survival benefit. The proportion of Black and White NSCLC patients not receiving CCRT and their outcomes have not been explored. Methods: Stage III NSCLC in Black and White patients diagnosed between 2004 and 2015 from the U.S. NCDB were included. Those with multiple tumors and who received surgery were excluded. Six groups were analyzed: CCRT (0-30 days between CT and RT), SCRT (31-120 days between CT and RT), RT (only RT), CT (only CT), No-RT-nor-CT (didn’t receive RT nor CT), and other (uncategorized). Univariate, multivariate, and Kaplan-Meier analyses were utilized (p<0.05). Results: A total of 22,459 Black (CCRT 42.3%, SCRT 7.6%, RT 13.8%, CT 15.1%, and No-RT-nor-CT 21.2%) and 138,477 White (CCRT 43.9%, SCRT 7.0%, RT 12.7%, CT 14.9%, and No-RT-nor-CT 21.5%) stage III NSCLCs were analyzed. Male gender and White race were positive predictive factors for receiving CCRT (Table). In Black patients SCRT (HR 1.1; 95% CI 1.04-1.17), RT only (HR 1.2; 95% CI 1.81-1.99), CT only (HR 1.4; 95% CI 1.36-1.49), and No RT or CT (HR 2.6; 95% CI 2.49-2.69) was associated with decreased overall survival (OS) compared to CCRT. In White patients, SCRT (HR, 1.0; 95% CI, 0.99-1.03) did not decrease OS compared to CCRT, whereas RT only (HR 1.8; 95% CI, 1.74-1.80), CT only (HR 1.3; 95% CI, 1.29-1.34), and No RT or CT (HR 2.6; 95% CI, 2.59-2.67) were associated with decreased OS. Median OS with CCRT was 18 months for Black patients, versus 16 months for White patients (p<0.0001). Conclusions: OS was highest when CCRT was given. A lower proportion of Black cases were managed with CCRT, but Black patients benefit more from CCRT and had improved OS than White patients. Despite the known benefits of CT and RT in stage III NSCLC, the second largest management cohort received neither RT nor CT.[Table: see text]
Radical surgery in malignnant pleural mesothelioma (MPM): An analysis of SEER database.
Authors: Wang Qian , Zhang Yaning , Ru Meng , Jiang Changchuan , Tran Jessica , Wisnivesky Juan P. , Veluswamy Rajwanth 
Published: June 2021

8554 Background: MPM is an aggressive malignnancy with poor overall prognosis. A combined treatment approach involving radical surgery (RS), radiation (RT) and chemotherapy (CT) provide improved survival compared to systemic treatment alone. Selecting patients who may benefit from RS is challenging. The NCCN guidelines recommend that up to T3N1M0 (Stage IIIA) epithelioid or biphasic MPM should be considered for multimodality therapy incorporating RS. However, the impact of clinical and pathologic features within each histologic subtype of MPM on RS outcomes is unknown. Methods: MPM patients from the SEER 18 program from 2004-2015 were identified. Cox proportional hazard regression models were used to examine the independent contribution of several clinical and pathologic features on overall survival (OS) in patients who received RS vs those that did not. Results: A total of 5,498 MPM patients were identified, of which 531 underwent RS. Overall, RS was associated with improved OS in the multivariate model adjusting for important clinical and pathological characteristics (Table). When stratifying according to histology, epithelioid subtype was linked to improved OS with RS despite of the presence male gender, age > 60 years old, T3, T4 or N2 or above disease; and the OS improved among those who also underwent CT ± RT with RS. Patients with sarcomatoid histology also had OS benefit from RS (HR=0.59, 95%CI: 0.37-0.93), even those that were > 60 years old, but not among those with more advanced disease (T3/4, N2/3). Sarcomatoid patients who received CT ± RT (HR = 0.52, 95%CI: 0.30-0.90) also experienced OS benefit. Among biphasic histology, no OS benefit was found overall (P = 0.11) or within other high-risk clinical features except for those who were treated CT ± RT (HR = 0.64, 95%CI: 0.45-0.90). Conclusions: Our findings demonstrate that the presence of high-risk clinical and pathologic features does not impact OS benefit of RS in epithelioid MPM, however should be considered when deciding on RS in sarcomatoid and biphasic histologies. Poor prognostic histology especially sarcomatoid subtype may experience improved survival with RS if in conjunction with other treatment modalities.[Table: see text]
Real-world evidence of cancer immunotherapy (CIT) combination treatment in first-line (1L) extensive-stage small cell lung cancer (ES-SCLC).
Authors: Nadler Eric S. , Vasudevan Anupama , Davies Kalatu , Wang Yunfei , Johnson Ann , Ogale Sarika 
Published: June 2021

8561 Background: Atezolizumab plus chemotherapy was the first CIT combination regimen approved for 1L treatment of ES-SCLC in 2019. This study investigated patient characteristics and treatment patterns for patients with ES-SCLC receiving this regimen in the real-world community oncology setting. Methods: This was a retrospective study including adult patients diagnosed with ES-SCLC between 01-Oct-2018 (after IMpower 133 publication in NEJM Sep-2018) and 31-Dec-2019, with follow-up through 31-March-2020 using The US Oncology Network electronic health records data. Descriptive analyses of patient characteristics and treatment patterns were conducted, with Kaplan-Meier (K-M) methods used to assess time to treatment discontinuation (TTD) and time to next treatment/death (TTNT). Results: Of the 408 patients included in this study, 267 (71.4%) received atezo+carboplatin+etoposide (Atezo+Chemo), 80 (21.4%) received carboplatin+etoposide (Chemo only) and the rest received other regimens. The Atezo+Chemo patients in the real-world cohort compared with the IMpower 133 trial (n = 201) were older (median age 68 vs. 64 years) and included fewer males (45% vs. 64%), fewer white race (73% vs. 81%), more patients with brain metastases at baseline (23% vs. 9%), and more patients with worse ECOG (2/3) performance-status score (24% vs. 0%). The median follow-up, TTD, and TTNT in months (mo) for the real-world cohort are presented in the table alongside the best comparable measures reported for the trial. Conclusions: Most patients in this real-world ES-SCLC cohort received the Atezo+Chemo regimen in the 1L setting. While the follow-up was much shorter and patients had worse baseline characteristics (age, brain metastases, ECOG) in the real-world setting compared to the IMpower 133 trial, the real-world median TTD in this descriptive analysis was found to be in line with the median duration of treatment in the trial. Further research with longer follow-up comparing the real-world effectiveness of the CIT and chemo regimens is needed.[Table: see text]
Cisplatin versus carboplatin for the treatment of limited-stage small cell lung cancer (LS-SCLC).
Authors: Azar Ibrahim , Austin Adam , Kim Seongho , Jang Hyejeong , Surapaneni Malini , Kurtz Daniel , Yazdanpanah Omid , Chopra Amit , Mehdi Syed , Mamdani Hirva 
Published: June 2021

8565 Background: Standard of care therapy for LS- SCLC is concurrent chemo-radiation (CRT) with a platinum-etoposide backbone. Cisplatin is traditionally the preferred platinum agent in the curative intent setting. Data comparing the efficacy of the less toxic carboplatin to cisplatin in LS-SCLC are lacking. Methods: Data from the National VA Cancer Cube were collected. Pathologically confirmed cases of LS-SCLC that received concurrent CRT with platinum-based multiagent chemotherapy were included. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median overall survival (OS) and hazard ratio (HR), respectively. Survival curves were compared by a Wald test. Results: 801 LS-SCLC patients who received carboplatin-based therapy (Carbo-SCLC) and 1018 who cisplatin-based therapy (Cis-SCLC) were included in the analysis. Median OS with Carbo-SCLC and Cis-SCLC were 2.13 years (95% CI 1.97-2.31) and 2.24 years (95% CI 2.09-2.4), respectively (HR=1.04;95% CI, 0.94-1.16; p=0.46). Subset analysis showed similar median OS for Carbo-SCLC and Cis-SCLC in patients with ECOG-PS of 0, 1 and 2, as well as patients in their 50s, 60s and >70. Multivariable regression analysis accounting for age and ECOG-PS shows a HR of 0.99 (95% CI 0.86-1.14; p=0.91). Conclusions: Concurrent CRT with carboplatin-etoposide was associated with similar OS compared to cisplatin-etoposide in LS-SCLC, irrespective of PS and age. Carboplatin’s advantageous toxicity profile and comparable OS indicate that it is an acceptable choice of platinum for LS- SCLC.[Table: see text]
First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA.
Authors: Reck Martin , Ciuleanu Tudor-Eliade , Cobo Manuel , Schenker Michael , Zurawski Bogdan , Janoski de Menezes Juliana , Richardet Eduardo , Bennouna Jaafar , Felip Enriqueta , Juan-Vidal Oscar , Alexandru Aurella , Sakai Hiroshi , Scherpereel Arnaud , Lu Shun , Paz-Ares Luis G. , Carbone David Paul , Memaj Arteid , Marimuthu Sathiya , Tran Phuong , John Tom 
Published: June 2021

9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]
Brigatinib in Japanese patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC): First results from the J-ALTA tyrosine kinase inhibitor (TKI)-naive expansion cohort.
Authors: Kondo Masashi , Sugawara Shunichi , Yokoyama Toshihide , Kumagai Toru , Nishio Makoto , Goto Koichi , Ohe Yuichiro , Seto Takashi , Yamamoto Nobuyuki , Kudou Kentarou , Asato Takayuki , Zhang Pingkuan , Nakagawa Kazuhiko 
Published: June 2021

9042 Background: Brigatinib is a next-generation ALK inhibitor with demonstrated activity against ALK mutations. We report primary analysis results with brigatinib in Japanese patients with ALK-positive NSCLC who have not previously been treated with an ALK TKI in the phase 2 J-ALTA study (NCT03410108). Methods: J-ALTA, a multi-cohort study, included a TKI-naive expansion cohort. Patients in the TKI-naive cohort received brigatinib 180 mg qd with 7-day lead-in at 90 mg. Primary endpoint was 12-month progression-free survival (PFS) as assessed by an independent-review committee (IRC). Secondary endpoints included confirmed objective response rate (ORR; IRC- and investigator-assessed); IRC-assessed PFS and duration of response (DoR); overall survival (OS); intracranial PFS (iPFS by IRC); and safety. Results: A total of 104 patients were enrolled in the whole study; of these, 32 patients had TKI-naive NSCLC (median age, 60.5 y; 94% had adenocarcinoma; 22% had baseline brain metastases; 25% received prior chemotherapy). As of September 29, 2020, median follow-up was 14.2 months and 27 patients remained on treatment. IRC-assessed 12-month PFS was 93% (90% CI, 79–98). Confirmed ORR was 97% (90% CI, 84–100) by IRC, with 2 complete responses and 29 partial responses. Median DoR as assessed by the IRC was not mature; median PFS, iPFS, and OS were not reached. In the TKI-naive cohort, treatment-emergent adverse events (TEAEs) were reported in all 32 patients (most common: increased creatine phosphokinase, 81%; hypertension, 59%; diarrhea, 47%). Grade ≥3 TEAEs were reported in 91% of patients in this cohort (most common: increased creatinine phosphokinase, 44%; hypertension, 34%; increased lipase, 19%) and 75% of all patients. Three cases (9.4%) of interstitial lung disease/pneumonitis were reported in the TKI-naive cohort; all were grade 1 and occurred after day 15 of brigatinib treatment. Dose discontinuations/interruptions/reductions due to AEs in the TKI-naive cohort were 0%/94%/66%, respectively, and in the total study population were 5%/72%/41%. AE frequency and profile were similar in the TKI-naive and overall cohorts. Conclusions: In the J-ALTA TKI-naive cohort, brigatinib demonstrated substantial efficacy and manageable safety in the Japanese patient population. Brigatinib remains one of the treatment options in Japanese patients. Clinical trial information: NCT03410108.