Updated Survival Results Research Articles

Long-term survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for oesophageal squamous cell carcinoma: insights from the EC-CRT-001 phase II trial

In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses. This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50mg/m2 of paclitaxel and 25mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4Gy in 28 fractions), and toripalimab (240mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170). With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR]=13.73, 95% CI 4.43-42.54, P<0.0001) and PFS (HR=32.08, 95% CI 8.57-120.10, P<0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P=0.082) and better PFS (HR=0.43, 95% CI 0.19-0.93, P=0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs (P=0.036). The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis. National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.

Palbociclib plus exemestane with GnRH agonist vs capecitabine in premenopausal patients with HR+/HER2- metastatic breast cancer: Updated survival results of the randomized phase 2 study Young-PEARL.

LBA1002 Background: The Young-PEARL study demonstrated improved progression free survival (PFS) (mPFS: 20.1 vs. 14.4 mo.) of exemestane plus palbociclib with ovarian function suppression (OFS) compared to capecitabine in premenopausal patients with HR+/HER2- metastatic breast cancer (mBC). Here we report updated survival outcomes with median follow-up of 54.8 months (data cutoff, November 30, 2023). Methods: Premenopausal women aged 19 years or older with HR+/HER2- BC who had relapsed or progressed during previous tamoxifen therapy were enrolled. One line of previous chemotherapy for mBC was allowed. The primary endpoint was PFS, which was defined as the time from C1D1 to disease progression or death. The key secondary endpoint was overall survival (OS). Other secondary endpoints included objective response rate (ORR) and toxicities. Results: 184 patients were randomly assigned to exemestane plus palbociclib with OFS (n=92) or capecitabine (n=92). Median age was 44.0 years (range, 28-58). Key efficacy and safety are shown in Table. Final analysis was conducted for 174 patients. The updated mPFS was 19.5 mo. (90% CI, 14.3-22.3) for exemestane + palbociclib + OFS compared with 14.0 mo. (90% CI, 11.7-18.7) for capecitabine (HR 0.75, P=0.04). mOS was 54.8 mo. (95% CI, 48.9-77.1) for palbociclib arm and 57.8 mo. (95% CI, 46.3-N/A) for capecitabine arm (HR 1.06, P=0.77). mPFS2 (from the date of 1st PD to 2nd PD) was significantly shorter in palbociclib arm than those of capecitabine arm (7.5 vs. 11.7 mo. P=0.02). Confirmed ORR based on the investigator assessments was 33.3% (95% CI, 23.6-43.1) for palbociclib and 33.7% (95% CI, 23.6-43.9) for capecitabine. Median treatment duration was 18.9 mo. (range 1.6-88.4) in palbociclib and 13.5 mo. (range 0.1-70.8) in capecitabine. In palbociclib arm, 86 (93.5%) experienced grade 3 or more TEAEs, mainly asymptomatic neutropenia (64.1%), compared to 41 (48.2%) patients with grade ≥3 TEAEs in the capecitabine arm, mainly Hand-Foot syndrome and neutropenia (18.8% for each). Conclusions: Young-PEARL study showed exemestane + palbociclib with OFS improves efficacy compared with capecitabine in terms of PFS, which did not lead to an OS benefit for patients with premenopausal HR+/HER2- mBC (median follow-up duration: 54.8 months). The overall safety profile of palbociclib and capecitabine continues to be manageable with longer follow-up. Clinical trial information: NCT02592746 . [Table: see text]

428P Total neoadjuvant FOLFIRINOX in patients with resectable locally advanced gastric and gastroesophageal junction cancer: Updated survival results

428P Total neoadjuvant FOLFIRINOX in patients with resectable locally advanced gastric and gastroesophageal junction cancer: Updated survival results

Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Updated survival results of DESTINY-Breast03.

1025 Background: DESTINY-Breast03 (NCT03529110), a randomized, multicenter, open-label, phase 3 study, assessed the efficacy and safety of T-DXd vs T-DM1 in pts with HER2+ mBC treated with ≥1 prior anti-HER2 regimen. Median (m) overall survival (OS) was not reached in either arm at the prior data cutoff (DCO; Jul 25, 2022). We report updated survival results, including efficacy and safety, after median duration of follow-up of 41 mo. Methods: Pts were randomized 1:1 to T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg once every 3 weeks. Primary endpoint was progression-free survival (PFS) by blinded independent central review (assessed at prior DCO); key secondary endpoint was OS. Other secondary endpoints included objective response rate (ORR), PFS, duration of response (DoR), PFS from time of randomization to progression on next line of therapy or death (PFS2), and safety. All secondary endpoints were based on investigator assessment. Results: 524 pts were randomized (T-DXd, n = 261; T-DM1, n = 263). As of Nov 20, 2023, median duration of follow-up was 43.0 mo (range, 0.0-62.9) for T-DXd and 35.4 mo (range, 0.0-60.9) for T-DM1. mOS (95% CI) was 52.6 mo (48.7-not evaluable [NE]) for T-DXd and 42.7 mo (35.4-NE) for T-DM1 (hazard ratio [HR], 0.73), with 110 (42.1%) and 126 (47.9%) OS events, respectively. OS rate (95% CI) at 36 mo was 67.6% (61.3-73.0%; T-DXd) vs 55.7% (49.2-61.7%; T-DM1). mPFS was 29.0 mo for T-DXd and 7.2 mo for T-DM1; PFS rate (95% CI) at 24 mo was 55.8% (49.1-62.0%; T-DXd) vs 20.6% (15.4-26.4%; T-DM1). mPFS2 was 45.2 mo (T-DXd) vs 23.1 mo (T-DM1). Median treatment duration was 18.2 mo (range, 0.7-56.6) with T-DXd vs 6.9 mo (range, 0.7-55.2) with T-DM1; rates of treatment-emergent adverse events (TEAEs) were consistent with prior DCO. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 16.7% of pts with T-DXd (4 new events [all grade 2] since prior DCO) vs 3.4% with T-DM1 (1 new event [grade 1]); neither arm had grade 4 or 5 events. Key efficacy and safety results are shown in the table. Conclusions: The superiority of T-DXd over T-DM1 was reinforced in this long-term analysis, as observed by clinically meaningful improvement in OS, PFS, and PFS2, consistent with prior DCO. The safety profile of T-DXd continues to be manageable with no cumulative toxicities observed with longer follow-up. Clinical trial information: NCT03529110 . [Table: see text]

Updated survival results of BBCAPX-II: Sintilimab combined with bevacizumab and CapeOx as first-line treatment in patients with RAS-mutant, microsatellite stable, unresectable metastatic colorectal cancer.

3563 Background: Microsatellite stable (MSS) and RAS-mutant metastatic colorectal cancer (mCRC) patients are characterized by an immunosuppressive microenvironment and a low response rate to immunotherapy. Sintilimab plus bevacizumab and CapeOX (BBCAPX) has proved its efficacy and safety in above unresectable mCRC patients (Ying Yuan et al. ASCO 2023 and Xuefeng Fang et al. ASCO 2022). Here, we report updated survival results of this single arm, open-label, phase 2 trial. Methods: Eligible patients were aged 18 to 75 years with histologically confirmed unresectable metastatic colorectal adenocarcinoma by multidisciplinary team, and had RAS gene mutation and confirmed MSS status. All patients received treatment with sintilimab (200 mg, day 1) plus bevacizumab (7.5mg/kg, day 1) and oxaliplatin (135 mg/m2, day 1) and capecitabine (1g/m2, bid, day 1-14) of each 21-day cycle. The primary endpoint included objective response rate (ORR) and adverse events. Secondary endpoint was disease control rate (DCR) and progression-free survival (PFS). Results: From April 2021 to December 2021, 25 patients were enrolled. The ORR was 84% and the DCR was 100%. Six (24%) patients underwent surgical treatment and unexpectedly achieved no evidence of disease status. At the data cut-off day (January 26, 2024), the median PFS in the full analysis set was 17.9 months (95% CI, 8.84-27), and the median PFS in the per-protocol set was 9.79 months (95% CI, 6.44-24.3). Median PFS was 23.7 months (95% CI, 4.8-NA) in the patients with only liver metastasis and 11.5 months (95% CI, 4.83-24.3) in the patients with other metastasis. The PFS rate at 6 months was 84% (95% CI, 70.8-99.7). The PFS rate at 12 months was 56% (95% CI, 39.6-79.3). The most frequent grade 3 or 4 TRAEs were neutropenia (3/25) and increased alanine transaminase (2/25). No grade 5 adverse events occurred during the study. Conclusions: The combination of sintilimab plus bevacizumab and CapeOx showed promising antitumor activity and manageable toxicity in RAS-mutant, MSS, unresectable mCRC. Patients with liver metastases presented better prognosis compared other metastases. Furthermore, we are currently launching a phase III, randomized, open-label, multicentric clinical trial (NCT05171660) to further analyze the effects, safety, and prognostic biomarkers of this regimen. Clinical trial information: NCT04194359 . [Table: see text]

Updated survival results of ALTER-C002: Anlotinib combined with CAPEOX as first-line treatment in RAS/BRAF wild-type unresectable metastatic colorectal cancer.

131 Background: Anlotinib is an oral multi-target tyrosine kinase inhibitor, mainly targeting VEGFR 1-3, FGFR 1-4, PDGFR a/b and c-kit. Previous trial had demonstrated that anlotinib monotherapy was effective and safe in advanced colorectal cancer. ALTER-C002 trial is an open-label, single-arm, phase II study, aimed to evaluate the efficacy and safety of anlotinib plus CAPEOX as first-line therapy in patients with RAS/ BRAF wild-type unresectable metastatic colorectal cancer (mCRC). The progression-free survival has been reported, preliminary results demonstrated significant antitumor activity and manageable toxicity, here we reported the overall survival results at the data cutoff of May 29, 2023. Methods: RAS/BRAF wild-type unresectable mCRC patients with no prior systemic treatment received anlotinib (12 mg p.o. qd, d1-d14, q3w), capecitabine (850 mg/m2 p.o., bid, d1-d14, q3w) and oxaliplatin (130 mg/m2 i.v., d1, q3w) for 6 cycles followed by anlotinib and capecitabine as maintenance therapy until disease progression. Tumor response was assessed every 6 weeks according to RECIST v1.1 by investigator. The primary endpoint was ORR, and secondary endpoints included safety, DCR, DOR and PFS. Results: From Nov 2019 to February 2021, 30 eligible patients were enrolled, of whom, median age was 60y (range, 32-72y), 26 (86.7%) had left colon or rectal cancer, and 25 (83.3%) had liver metastases. In previous reports, ORR, DCR, and median PFS were 76.7%, 93.3%, and 11.3 months, respectively. At a Median follow-up of 31.7 months (95% CI, 27.8-35.6), the median OS was 29.7 months (95% CI, 21.2-38.2), the 24-month OS rate was 55.0% (95%CI, 35.4-70.9%) and the 30-month OS rate was 40.6% (95%CI:21.6-58.9%). Conclusions: Anlotinib combined with oxaliplatin and capecitabine achieved considerable OS and showed potential efficacy as first-line therapy for mCRC with manageable toxicity profiles. Clinical trial information: NCT04080843 .

Trastuzumab deruxtecan in previously treated patients with HER2-positive metastatic breast cancer: updated survival results from a phase II trial (DESTINY-Breast01)

Primary analysis of the multicenter, open-label, single-arm, phase II DESTINY-Breast01 trial (median follow-up 11.1 months) demonstrated durable antitumor activity with trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1). We report updated cumulative survival outcomes with a median follow-up of 26.5 months (data cut-off 26 March 2021). Patients with HER2-positive mBC resistant or refractory to T-DM1 received T-DXd 5.4 mg/kg intravenously every 3 weeks until disease progression, unacceptable adverse events, or withdrawal of consent. The primary endpoint was confirmed objective response rate (ORR) by independent central review (ICR). Secondary endpoints included overall survival (OS), duration of response (DoR), progression-free survival (PFS), and safety. The ORR by ICR was 62.0% [95% confidence interval (CI) 54.5% to 69.0%] in patients who received T-DXd 5.4 mg/kg every 3 weeks (n= 184). Median OS was 29.1 months (95% CI 24.6-36.1 months). Median PFS and DoR were 19.4 months (95% CI 14.1-25.0 months) and 18.2 months (95% CI 15.0 months-not evaluable), respectively. Drug-related treatment-emergent adverse events (TEAEs) were observed in 183 patients (99.5%), and 99 patients (53.8%) had one or more grade ≥3 TEAEs. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 15.8% of patients (n= 29), of which 2.7% (n= 5) were grade5. These updated results provide further evidence of sustained antitumor activity of T-DXd with a consistent safety profile in heavily pretreated patients with HER2-positive mBC.

Breast density reduction as a predictor for prognosis in premenopausal women with estrogen receptor-positive breast cancer: an exploratory analysis of the updated ASTRRA study.

While the relationship between mammographic breast density reduction (MDR) and endocrine therapy efficacy has been reported in estrogen receptor (ER)-positive breast cancer, it is still unclear in premenopausal women, especially in the case of adding ovarian function suppression (OFS) to antihormone therapy. The authors investigated the impact of MDR on prognosis stratified by treatment based on the updated results of the ASTRRA trial. The ASTRRA trial, a randomized phase III study, showed that adding OFS to tamoxifen (TAM) improved survival in premenopausal women with estrogen receptor-positive breast cancer after chemotherapy. The authors updated survival outcomes and assessed mammography before treatment and the annual follow-up mammography for up to 5 years after treatment initiation. Mammographic density (MD) was classified into four categories based on the Breast Imaging-Reporting and Data System. MDR-positivity was defined as a downgrade in MD grade on follow-up mammography up to 2 years after randomization, with pretreatment MD grade as a reference. The authors evaluated MDR in 944 of the 1282 patients from the trial, and 813 (86.2%) had grade III or IV MD. There was no difference in the MDR-positivity rate between the two treatment groups [TAM-only group (106/476 (22.3%)) vs. TAM+OFS group (89/468 (19.0%)); P =0.217). MDR-positivity was significantly associated with better disease-free survival (DFS) in the TAM+OFS group (estimated 8-year DFS: 93.1% in MDR-positive vs. 82.0% in MDR-negative patients; HR: 0.37; 95% CI: 0.16-0.85; P =0.019), but not in the TAM-only group ( Pinteraction =0.039). MDR-positive patients who received TAM+OFS had a favorable DFS compared to MDR-negative patients who received only TAM (HR: 0.30; 95% CI: 0.13-0.70; P =0.005). Although the proportion of MDR-positive patients was comparable between both treatment groups, MDR-positivity was independently associated with favorable outcomes only in the TAM+OFS group.

P2.06-11 Camrelizumab Plus Apatinib as First-Line Treatment for Advanced Squamous Non-small-Cell Lung Cancer: Updated Survival Results of a Phase 2 Trial

P2.06-11 Camrelizumab Plus Apatinib as First-Line Treatment for Advanced Squamous Non-small-Cell Lung Cancer: Updated Survival Results of a Phase 2 Trial

376O Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Updated survival results of the randomized, phase III DESTINY-Breast04 study

376O Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Updated survival results of the randomized, phase III DESTINY-Breast04 study

Effect of 1 H-NMR serum lipoproteins on immunotherapy response in advanced triple-negative breast cancer patients.

We previously reported the results of a phase II trial of anti-PD-1 antibody plus anti-vascular endothelial growth factor receptor 2 inhibitors and eribulin in heavily pretreated advanced triple-negative breast cancer with a favorable objective response rate (ORR) of 37.0% (NCT04303741). Here we report updated survival outcomes and serum metabolite changes of the study. Proton nuclear magnetic resonance spectroscopy was used to detect metabolite dynamics and explore biomarkers for response. We found that treatment-sensitive patients had higher very low-density lipoprotein-related metabolite expression at baseline. A lipid proteomics model consisting of six metabolites predicted ORR and progression-free survival at 6 months with area under the receiver operating characteristic curves of 0.88 and 0.87, respectively. Serum asparagine and sarcosine concentrations were significantly higher after treatment in treatment-resistant patients. In conclusion, we constructed a model consisting of six metabolites to identify patients who benefit more from the triplet treatment, and asparagine and sarcosine may be associated with treatment resistance.

Abstract GS2-02: GS2-02 Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated survival results of the randomized, phase 3 study DESTINY-Breast03

Abstract Background: Trastuzumab deruxtecan (T-DXd) is approved in the United States and European Union for use in patients (pts) with HER2+ unresectable/metastatic breast cancer (mBC) after ≥1 prior anti–HER2 regimen(s). Approval was based on the randomized, multicenter, open-label, phase 3 DESTINY-Breast03 study (NCT03529110), in which T-DXd demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with trastuzumab emtansine (T-DM1). At the primary interim analysis (data cutoff May 21, 2021), the risk of disease progression or death was reduced by 72% with T-DXd (P &amp;lt; 0.001; Cortes et al. N Engl J Med 2022). Overall survival (OS) data were immature for both treatment groups; although the prespecified cutoff for significance was not reached (NR), a trend toward benefit with T-DXd was observed. With further follow-up, we report results from the prespecified OS analysis of DESTINY-Breast03 (data cutoff July 25, 2022), including updated efficacy and safety. Methods: Pts with HER2+ mBC previously treated with trastuzumab and a taxane in either the metastatic setting or (neo)adjuvant setting with progression within 6 mo of therapy, who could have received pertuzumab, were randomly assigned 1:1 to receive T-DXd 5.4 mg/kg every 3 weeks (Q3W) or T-DM1 3.6 mg/kg Q3W until disease progression. The primary endpoint was PFS by blinded independent central review (BICR). The key secondary endpoint was OS (80% powered at 2-sided significance level of 5%); other secondary endpoints included objective response rate (ORR), duration of response (DoR), PFS based on investigator assessment, and safety. Results: 524 pts received either T-DXd (n = 261) or T-DM1 (n = 263). As of the updated data cutoff, median duration of study follow-up was 28.4 mo (range, 0.0-46.9 mo) for T-DXd and 26.5 mo (range, 0.0-45.0 mo) for T-DM1. Median treatment duration was 18.2 mo (range, 0.7-44.0 mo) for T DXd and 6.9 mo (range, 0.7-39.3 mo) for T-DM1. The risk of death was reduced by 36% (HR, 0.64; P = 0.0037) with T-DXd; median OS (mOS) was NR (95% CI, 40.5 mo-not evaluable [NE]), with 72 (27.6%) OS events, for T-DXd vs NR (95% CI, 34.0 mo-NE), with 97 (36.9%) OS events, for T-DM1. Landmark 12-mo OS rate was 94.1% (95% CI, 90.4-96.4) for T-DXd vs 86.0% (95% CI, 81.1-89.8) for T-DM1; 24-mo OS rate was 77.4% (95% CI, 71.7-82.1) for T-DXd vs 69.9% (95% CI, 63.7-75.2) for T-DM1. The P value for OS crossed the prespecified boundary (P = 0.013) and was statistically significant. mPFS by BICR was 28.8 mo (95% CI, 22.4-37.9 mo) with T-DXd, compared with 6.8 mo (95% CI, 5.6-8.2 mo) with T-DM1; HR, 0.33; nominal P &amp;lt; 0.000001. Key efficacy and safety results are shown in the table. Grade ≥3 treatment-emergent adverse events were experienced by 56.4% of T-DXd-treated pts and 51.7% of T DM1-treated pts. Drug-related interstitial lung disease/pneumonitis, as evaluated by an independent adjudication committee, was experienced by 39 pts (15.2%) in the T-DXd arm and 8 pts (3.1%) in the T DM1 arm; no adjudicated drug-related grade 4 or 5 events were observed in pts who received T-DXd. Conclusions: Updated results confirm the superiority of T-DXd compared with T-DM1 for pts with HER2+ mBC previously treated with an anti-HER2 therapy, with highly clinically meaningful and statistically significant benefit in OS and PFS and a manageable safety profile with longer treatment duration. Editorial Acknowledgment Under the guidance of authors, assistance in medical writing and editorial support was provided by Laura Halvorson, PhD, and Rachel Hood, PhD, of ApotheCom, and was funded by Daiichi Sankyo. Funding This study was funded by Daiichi Sankyo and AstraZeneca. Table. Summary of Efficacy Results for T-DXd and T-DM1 Citation Format: Sara Hurvitz, Roberto Hegg, Wei-Pang Chung, Seock-Ah Im, William Jacot, Vinod Ganju, Joanne Win Yang Chiu, Binghe Xu, Erika Hamilton, Srinivasan Madhusudan, Hiroji Iwata, Sevilay Altintas, Jan-Willem Henning, Giuseppe Curigliano, José Manuel Pérez-García, Anton Egorov, Yali Liu, Jillian Cathcart, Shahid Ashfaque, Javier Cortés. GS2-02 Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated survival results of the randomized, phase 3 study DESTINY-Breast03 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS2-02.

Updated survival outcomes with ivosidenib in patients with previously treated IDH1-mutated intrahepatic-cholangiocarcinoma: an Italian real-world experience.

The results of the phase III ClarIDHy trial led to the FDA approval of ivosidenib as a therapeutic option for patients with locally advanced or metastatic cholangiocarcinoma (CCA) harboring isocitrate dehydrogenase 1 (IDH1) mutations. We recently published the first data on the use of ivosidenib in a real-world setting. Here we report the updated survival results of 11 patients with locally advanced or metastatic IDH1-mutated CCA who received ivosidenib in clinical practice. Patients treated with ivosidenib as second- and third-line treatments for advanced CCA have been collected with the aim to evaluate the survival outcomes. A molecular study has been performed by next generation sequencing essay. Overall, 11 patients were included. After a median follow-up of 13.7 months, median progression-free survival from the start of treatment with ivosidenib was 4.4 months (95% CI: 2.0-5.8), whereas median overall survival was 15 months (95% CI: 6.6-15.0) regardless of treatment line. Disease control rate was 63%, with two patients achieving a partial response (18%). Eighteen percent of patients experienced at least one treatment-related adverse events (AEs), but no grade ⩾3 was reported. The most frequently observed grade 2 AEs were prolonged QT interval and hypomagnesemia. A molecular profiling was performed on 8 out of 11 patients, highlighting TP53, BAP1, CDKN2A, and CDKN2B as the most common co-altered genes in these patients. The present update confirms the results of our previous real-world experience on the use of ivosidenib in IDH1-mutated CCA. Real-world evidence on larger numbers of patients is needed to confirm our findings.

SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma: A Systematic Review and Pooled Analysis of Treatment Outcomes.

Simple SummarySMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare but locally aggressive malignancy which usually presents very late with invasion into the orbits and intracranium, and compression of adjacent cranial nerves and their branches at diagnosis, and has a poor survival outcome. So far, less than 200 cases have been reported. The optimal treatment strategy for this rare but intractable malignancy is yet to be determined. We performed a systematic review and included patients treated at our institution for treatment outcome and survival analysis. Multivariable analysis revealed that T4b disease at diagnosis was the only prognostic factor of overall survival. In view of the extreme challenge of managing this malignancy, we are initiating a phase II trial on tazemetostat, an EHZ2 inhibitor, as induction therapy with systemic chemotherapy followed by radical surgery or chemoradiation, and as maintenance therapy for previously untreated stage III to IVA SMARCB1 (INI-1)-deficient sinonasal carcinoma.(1) Background: SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare sinonasal malignancy; since its discovery and description in 2014, less than 200 cases have been identified. It is almost impossible to perform randomized-controlled trials on novel therapy to improve treatment outcomes in view of its rarity. We performed a systematic review of all the published case reports/series and included our patients for survival analysis. (2) Methods: In this systematic review, we searched from PubMed-MEDLINE, EMBASE, Scopus, Cochrane Library, CINAHL, and Google Scholar for individual patient data to identify and retrieve all reported SMARCB1-deficient sinonasal carcinoma. Clarification on treatment details and the most updated survival outcomes from all authors of the published case reports/series were attempted. Survival analysis for overall survival (OS) and identification of OS prognostic factors were performed. This systematic review was registered with PROSPERO (CRD42022306671). (3) Results: A total of 67 publications were identified from the systematic review and literature search. After excluding other ineligible and duplicated publications, 192 patients reported were considered appropriate for further review. After excluding duplicates and patients with incomplete pretreatment details and survival outcomes, 120 patients were identified to have a complete set of data including baseline demographics, treatment details, and survival outcomes. Together with 8 patients treated in our institution, 128 patients were included into survival analysis. After a median follow up of 17.5 months (range 0.3–149.0), 50 (46.3%) patients died. The 1-year, 2-year and 3-year OS rates were 84.3% (95% CI % 77.6–91.0), 62.9% (95% CI 53.1–72.7), and 51.8% (95% CI 40.8–62.8), respectively, and the median OS was 39.0 months (95% CI 28.5–49.5). Males (p = 0.029) and T4b disease (p = 0.013) were significant OS prognostic factors in univariable analysis, while only T4b disease (p = 0.017) remained significant in multivariable analysis. (4) Conclusions: SMARCB1-deficient sinonasal carcinoma is an extremely aggressive sinonasal malignancy with a dismal prognosis. Early diagnosis and a multimodality treatment strategy are essential for a better treatment and survival outcome.

Breast density reduction as a predictor for prognosis in premenopausal women with hormone receptor–positive breast cancer: A retrospective analysis of the ASTRRA study.

531 Background: While the relationship between mammographic breast density (MD) decline and anti-hormone therapy efficacy has been reported in estrogen-receptor (ER)-positive breast cancer, it is still unclear in premenopausal women and in the case of adding ovarian function suppression (OFS) to anti-hormone therapy. We aimed to investigate the MD reduction (MDR) rate and impact of MDR on prognosis stratified by treatment from the updated result of the ASTRRA trial. Methods: ASTRRA trial, a randomized phase 3 study, showed that adding ovarian function suppression (OFS) to tamoxifen (TAM) improved survival in premenopausal women with ER+ breast cancer after chemotherapy. We updated survival outcomes with a median follow-up of 108 months. We assessed mammography taken before treatment and the follow-up mammography taken annually for up to five years after initiation of treatment. MD was classified into four categories based on the Breast Imaging Reporting and Data System. MDR positivity was defined as a downgrade in MD among follow-up mammography up to two years after randomization, with the pretreatment MD grade as a reference. Results: Among the 1,293 patients from ASTRRA trial, we successfully evaluated MDR in 947 patients, of which 796 (83.4%) belong to high MD (grade C or D). The patient characteristics were similar between the entire ASTRRA trial and the subgroup with available MDR. There was no difference in MDR-positive rate between two treatment groups (106 of 477 [22.2%] in TAM-only group vs. 87 of 470 [18.5%] in TAM + OFS group, P =.156). MDR-positivity was significantly associated with better disease-free survival (DFS) in TAM + OFS group (estimated 8-year DFS: 92.9% in MDR-positive vs. 82.2% in MDR-negative, P =.013), but did not in TAM-only group (estimated 8-year DFS: 80.3% in MDR-positive vs. 80.2% in MDR-negative, P =.927; Pinteraction =.025). Simialr trends were observed in terms of recurrence-free survival, distant metastasis-free survival (DMFS), locoregional-free survival, and overall survival. In addition, MDR-positivity was an independent factor for favorable DFS (adjusted hazard ratio [HR], 0.37; 95% CI, 0.16 to 0.86; P =.021) and DMFS (adjusted HR, 0.35; 95% CI, 0.13 to 0.98; P =.045) in TAM + OFS group. Conclusions: Although the proportion of patients with MDR-positive was comparable between the two treatment groups, MDR-positive was independently associated with favorable outcomes only in TAM + OFS group. Future work is warranted to verify the mechanism by which the association between MDR and clinical benefit differs according to the treatment group. Clinical trial information: NCT00912548.

481P - Updated survival outcomes of the phase II study of low starting dose of afatinib as first-line treatment in patients with EGFR mutation-positive non-small cell lung cancer (KTORG1402)

BackgroundThe phase II trial evaluated the efficacy and safety of low starting dose of afatinib in patients with advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). In primary analysis, progression free survival (PFS) met the primary endpoint. Here, we report updated survival outcomes. MethodsThis study was a multi-center, single-arm, open-label phase II trial. Treatment-naïve patients with common EGFR mutation-positive NSCLC were treated with afatinib starting at a dose of 20 mg/day. If tolerated, the dose is increased by 10- mg increments up to 50mg/day. PFS and overall survival (OS) were re-evaluated at the final data cut-off point (October 2018). Results46 patients were enrolled. Median age was 73 years (range, 43-86). The median follow-up was 31.9 months. Median PFS of entire population was 15.2 months (95% confident interval (CI), 13.2–21.2), and 2-year PFS rate was 27.7% (95% CI, 17.1-44.7). Median OS was not estimated, and the 2-year overall survival was 76.1% (95% CI, 64.7-89.5). Performance status (PS) and existence of brain metastases at study entry were revealed to have significant impact on the survival with Cox-regression test. Among patients with disease progression on afatinib (n = 36), rebiopsy was performed on 29 patients, and T790M was proved positive on 14 patients. Twelve out of the 14 patients positive for T790M received osimertinib as a second line therapy. Median time from enrollment to progression on the osimertinib (PFS2) was 32.6 months (95%CI: 20.5-NE). ConclusionsLow starting dose afatinib therapy demonstrated promising OS outcome. PS and existence of brain metastases were predictive factors of this therapy. Clinical trial identificationUMIN 000016444. Legal entity responsible for the studyKyoto Thoracic Oncology Research Group. FundingHas not received any funding. DisclosureT. Yokoyama: Honoraria (self): Boehringer Ingelheim Japan; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Ono pharmaceutical; Honoraria (self): MSD. H. Yoshioka: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Eli Lilly Japan; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis; Honoraria (self): Merck Serono; Honoraria (self): Kyowa Kirin; Honoraria (self): AstraZeneca; Honoraria (self): Ono pharmaceutical; Honoraria (self): Daiichi Sankyo; Honoraria (self): MSD. D. Fujimoto: Honoraria (self), Research grant / Funding (self): AstraZeneca KK; Honoraria (self): Ono Pharmaceutical Co Lt; Honoraria (self): Bristol-Myers Squibb Co Ltd; Honoraria (self): Taiho Pharmaceutical Co ; Honoraria (self), Research grant / Funding (self): Chugai Pharmaceutical Co Ltd; Honoraria (self): MSD KK; Honoraria (self): Boehringer Ingelheim Japan Inc; Honoraria (self): Eli Lilly Japan KK. K. Hirano: Honoraria (self): Boehringer Ingelheim Japan. T. Ishida: Honoraria (self): Boehringer Ingelheim Japan. T. Hirai: Research grant / Funding (institution): Boehringer Ingelheim Japan. All other authors have declared no conflicts of interest.

Nivolumab plus Ipilimumab for Advanced NSCLC: Updated Survival Results

A prior report of the phase III trial CheckMate 227 trial (NEJM JW Oncol Hematol Jul 2018 and N Engl J Med 2018; 378:2093) showed that

Cost-effectiveness of tumor-treating fields added to maintenance temozolomide in patients with glioblastoma: an updated evaluation using a partitioned survival model.

A first cost-effectiveness analysis has raised a strong concern regarding the cost of tumor treatment fields (TTF) added to maintenance temozolomide for patients with glioblastoma. This evaluation was based on effectiveness outcomes from an interim analysis of the pivotal trial, moreover it used a "standard" Markov model. Our objective was to update the cost-effectiveness evaluation using the more flexible potential of the "partitioned survival" model design and using the latest effectiveness data. We developed the model with three mutually exclusive health states: stable disease, progressive disease, and dead. Good fit parametric models were developed for overall survival and progression free survival and these generated clinically plausible extrapolations beyond the observed data. We adopted the perspective of the French national health insurance and used a 20-year time horizon. Results were expressed as cost/life-years (LY) gained (LYG). The base case model generated incremental benefit of 0.604 LY at a cost of €453,848 which, after 4% annual discounting of benefits and costs, yielded an incremental cost effectiveness ratio (ICER) of €510,273/LYG. Using sensitivity analyses and bootstrapping methods results were found to be relatively robust and were only sensitive to TTF device costs and the modelling of overall survival. To achieve an ICER below €100,000/LYG would require a reduction in TTF device cost of approximately 85%. Using a different type of model and updated survival outcomes, our results show TTF remains an intervention that is not cost-effective, which greatly restrains its diffusion to potentially eligible patients.

Abstract CT115: Updated survival results of the KEYNOTE-040 study of pembrolizumab vs standard-of-care chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma

Abstract Background: It was known that survival data were outstanding on several patients (pts) when the final analysis of the multinational, open-label, phase 3 KEYNOTE-040 study (NCT02252042) of pembro vs SOC for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) was performed. This abstract presents OS and PFS data using the same data cutoff date but with full survival acquisition. Methods: 495 pts with SCC of the oral cavity, oropharynx, hypopharynx, or larynx who had recurrence or PD after a platinum-containing regimen were randomized 1:1 to pembro 200 mg Q3W for 24 mo or investigator's choice of methotrexate, docetaxel, or cetuximab. Primary end point was OS in the ITT population. Key secondary end points included OS in the PD-L1 combined positive score (CPS) ≥1 population and PFS in the ITT and CPS ≥1 populations. OS and PFS in the PD-L1 tumor proportion score (TPS) ≥50% population were prespecified exploratory end points. Response was assessed per RECIST v1.1 by blinded, independent central review. Results: With full acquisition of survival data, HR was 0.80 (95% CI, 0.65-0.98) (nominal P = 0.0161) for OS and 0.96 (95% CI, 0.79-1.16) (nominal P = 0.33) for PFS in the ITT population. Median (95% CI) OS was 8.4 mo (6.4-9.4) for pembro vs 6.9 mo (5.9-8.0) for SOC; median PFS was 2.1 mo (2.1-2.3) vs 2.3 mo (2.1-2.8). Pembro benefit was greater in pts with PD-L1 CPS ≥1 and TPS ≥50% (Table). Conclusions: Pembro provided a clinically meaningful prolongation of OS compared with SOC in pts with R/M HNSCC. With full acquisition of survival data and compared with the previous analysis, the HR for OS decreased from 0.81 to 0.80, and the P value decreased from 0.0204 to 0.0161. There continued to be an enhanced benefit for pembro in pts with PD-L1–expressing tumors. Along with previously presented safety data, these results provide stronger support for the benefit of pembro in pts with R/M HNSCC. Table. OS and PFS in the PD-L1 CPS ≥1 and TPS ≥50% Populations CPS ≥1TPS ≥50%Pembron = 196SOCn = 191Pembro n = 64SOCn = 65OSMedian (95% CI), mo8.7 (6.9-11.4)7.1 (5.7-8.3)11.6(8.3-19.5)6.6(4.8-9.2)HR (95% CI)0.74 (0.58-0.93)0.53 (0.35-0.81)Pa0.00490.0014PFSMedian (95% CI), mo2.2 (2.1-3.0)2.3 (2.1-3.0)3.5(2.1-6.3)2.1(2.0-2.4)HR (95% CI)0.86 (0.69-1.06)0.58 (0.39-0.86)Pa0.080.003aNominal one-sided P value stratified by the randomization stratification factors. Citation Format: Denis Soulieres, Ezra Cohen, Christophe Le Tourneau, Jose Dinis, Lisa Licitra, Myung-Ju Ahn, Ainara Soria, Jean-Pascal Machiels, Nicolas Mach, Ranee Mehra, Barbara Burtness, Pingye Zhang, Jonathan Cheng, Ramona Swaby, Kevin J. Harrington. Updated survival results of the KEYNOTE-040 study of pembrolizumab vs standard-of-care chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT115.

Erratum to updated survival outcomes and analysis of long-term survivors from the MORE study on safety and efficacy of radioembolization in patients with unresectable colorectal cancer liver metastases.

[This corrects the article DOI: 10.21037/jgo.2017.03.10.].