Median Prolonged Progression-free Survival Research Articles

Chemotherapy plus or minus bevacizumab for platinum-sensitive ovarian cancer patients recurring after a bevacizumab containing first line treatment: The randomized phase 3 trial MITO16B-MaNGO OV2B-ENGOT OV17.

5506 Background: Bevacizumab (BEV) is approved in recurrent ovarian cancer (rOC) for patients not previously treated with the drug. Our study aimed at evaluating whether the addition of BEV to a platinum-based chemotherapy prolongs progression-free survival (PFS) for rOC patients who had already received it during first line. Methods: FIGO stage IIIB-IV rOC patients relapsing at least 6 months after last dose of platinum, who had received BEV during first-line treatment, ECOG PS≤2, were randomized to 6 cycles of platinum-based doublets (carboplatin/paclitaxel or carboplatin/gemcitabine or carboplatin/PLD) with or without BEV administered concomitant with chemotherapy and as maintenance until disease progression. The primary endpoint is PFS. With 90% power in detecting a 0.67 HR, with 2-sided α error 0.05, 265 events were needed. All efficacy analyses are done on an intention-to-treat basis. PFS and OS curves are estimated by Kaplan-Meier method, and compared with a two-sided log-rank test. Toxicity is graded according to NCI-CTCAE v 4.0. Results: 405 pts were enrolled. Median age was 61; 64% of patients had progressed ≥12 months after last dose of platinum and 72% of patients after completion of first-line BEV maintenance. With a median follow-up of 20.3 months, 304 PFS events and 147 deaths were recorded. Median PFS was 8.8 months and 11.8 months without and with BEV, respectively (HR 0.51, 95%CI: 0.41-0.64, p < 0.001). Median OS was 27.1 months and 26.7 months without and with BEV, respectively (HR 1.00, 95%CI: 0.73-1.39, p = 0.98). Severe (≥G3) hypertension (27.5% vs 9.7%, p < 0.001) and proteinuria (4% vs 0, p = 0.007) were more frequent with BEV. Conclusion: This study shows that for rOC patients previously treated with BEV in first line relapsing ≥6 months after last platinum, rechallenge with BEV in combination with platinum-based doublets is associated with a significantly prolonged PFS, with no unexpected toxicity.Supported by Roche. Clinical trial information: NCT01802749.

Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma

ImportancePatients with borderline-resectable pancreatic ductal adenocarcinoma have historically poor outcomes with surgery followed by adjuvant chemotherapy. Evaluation of a total neoadjuvant approach with highly active therapy is warranted.ObjectiveTo evaluate the margin-negative (R0) resection rate in borderline-resectable pancreatic ductal adenocarcinoma after neoadjuvant FOLFIRINOX (fluorouracil, irinotecan, and oxaliplatin) therapy and individualized chemoradiotherapy.Design, Setting, and ParticipantsA single-arm, phase 2 clinical trial was conducted at a large academic hospital with expertise in pancreatic surgery from August 3, 2012, through August 31, 2016, among 48 patients with newly diagnosed, previously untreated, localized pancreatic cancer determined to be borderline resectable by multidisciplinary review, who had Eastern Cooperative Oncology Group performance status 0 or 1 and adequate hematologic, renal, and hepatic function. Median follow-up for the analysis was 18.0 months among the 30 patients still alive at study completion.InterventionsPatients received FOLFIRINOX for 8 cycles. Upon restaging, patients with resolution of vascular involvement received short-course chemoradiotherapy (5 Gy × 5 with protons) with capecitabine. Patients with persistent vascular involvement received long-course chemoradiotherapy with fluorouracil or capecitabine.Main Outcomes and MeasuresThe primary outcome was R0 resection rate; secondary outcomes were median progression-free survival (PFS) and median overall survival (OS).ResultsOf the 48 eligible patients, 27 were men and 21 were women, with a median age of 62 years (range, 46-74 years). Of the 43 patients who planned to receive 8 preoperative cycles of chemotherapy, 34 (79%) were able to complete all cycles. Twenty-seven patients (56%) had short-course chemoradiotherapy, while 17 patients (35%) had long-course chemoradiotherapy. R0 resection was achieved in 31 of the 48 eligible patients (65%; 95% CI, 49%-78%). Among the 32 patients who underwent resection, the R0 resection rate was 97% (n = 31). Median PFS among all eligible patients was 14.7 months (95% CI, 10.5 to not reached), with 2-year PFS of 43%; median OS was 37.7 months (95% CI, 19.4 to not reached), with 2-year OS of 56%. Among patients who underwent resection, median PFS was 48.6 months (95% CI, 14.4 to not reached) and median OS has not been reached, with a 2-year PFS of 55% and a 2-year OS of 72%.Conclusions and RelevancePreoperative FOLFIRINOX followed by individualized chemoradiotherapy in borderline resectable pancreatic cancer results in high rates of R0 resection and prolonged median PFS and median OS, supporting ongoing phase 3 trials.Trial RegistrationClinicalTrials.gov Identifier: NCT01591733

Apatinib: A Review in Advanced Gastric Cancer and Other Advanced Cancers.

Apatinib [Aitan® (brand name in China)], also known as rivoceranib, is a novel, small molecule, selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and is the second anti-angiogenic drug to be approved in China for the treatment of advanced or metastatic gastric cancer. This article summarizes the pharmacological properties of apatinib and reviews its clinical use in chemotherapy-experienced patients with advanced gastric adenocarcinoma, including gastroesophageal adenocarcinoma (GEA), or with other advanced cancers such as non-small cell lung cancer (NSCLC), breast cancer, gynaecological cancers, hepatocellular carcinoma (HCC), thyroid cancer and sarcomas. As third- or subsequent-line therapy, oral apatinib significantly prolonged median progression-free survival (PFS) and overall survival (OS) compared with placebo and had a manageable safety profile in Chinese patients with advanced or metastatic gastric cancer or GEA participating in randomized, double-blind, multicentre, phase 2 and 3 trials. More limited evidence also supports it use as subsequent-line treatment in Chinese patients with other advanced or metastatic solid tumours, including NSCLC, breast cancer and HCC. Further clinical experience and long-term pharmacovigilance data are required to more definitively establish the efficacy and safety profile of apatinib, including its use in combination with other chemotherapy agents and its role in the management of other types of advanced or metastatic solid tumours. In the meantime, given its convenient administration regimen and the limited treatment options and poor prognosis for patients with advanced or metastatic solid tumours, apatinib is an important, emerging treatment option for adult patients with advanced gastric adenocarcinoma or GEA who have progressed or relapsed after chemotherapy.

Impact of oophorectomy and hormone suppression in low grade endometrial stromal sarcoma: A multicenter review

ObjectivesLow grade endometrial stromal sarcoma (LG-ESS) is a rare cancer with an indolent course. We aimed to assess the effectiveness of adjuvant hormonal suppression (HT) with or without oophorectomy (BSO) in prolonging progression free survival (PFS) and overall survival (OS) in patients with LG-ESS. MethodsWe performed a multi-institutional retrospective review of patients treated for low grade LG-ESS from 1985 to 2014. Demographics, treatment and recurrence data were abstracted from medical records. Pathologic diagnosis was confirmed by a gynecologic pathologist. Long-term patient-reported outcomes were obtained via mailed survey. ResultsOne-hundred-twelve patients underwent surgery for LG-ESS; 59 had postoperative data with a median follow-up of 55months (1–325months). The mean age at diagnosis was 48.5years (22–82years). Forty-nine (61%) had stage I disease. The most common presenting symptoms were abnormal uterine bleeding (38%) and pelvic mass (17%). Seventy-one (63%) patients had BSO at the time of diagnosis. Of the 59 patients with postoperative follow-up information, 49 (73%) underwent BSO, 26 (44%) received HT, 20 (33%) were expectantly managed, and 6 (10%) received chemotherapy, radiation or both. Median PFS for the entire group was 53months and OS was 63months. PFS for those who underwent BSO compared with those who retained their ovaries was 38 vs 11months, p=0.071. PFS for HT vs no HT was 28 vs 23months, p=0.77. ConclusionsConsistent with prior series, our results support BSO to prolong PFS in LG-ESS but are limited by sample size. Larger studies with more complete follow-up are needed to determine the effect of adjuvant hormonal suppression.

Monitoring minimal residual disease in canine lymphomas treated with modified L-COP or L-CHOP protocols.

Heteroduplex polymerase chain reaction for antigen receptor rearrangements (hPARR) was developed to monitor minimal residual disease (MRD) in canine B- and T-cell lymphomas treated with the modified L-COP or L-CHOP protocol. Thirty-five dogs were recruited in this study and their neoplastic lineages were determined by immunophenotyping with Pax5 and CD3. Peripheral blood leukocytes were collected prior to and during chemotherapy in weeks 4, 9 and 13 to detect MRD by hPARR. Twenty-eight dogs (80%) had B-cell lymphoma while seven dogs (20%) had T-cell lymphoma. A monoclonal band was detected in 11 cases that showed complete or partial remission before tumour relapse and no response to the current treatment without statistical difference in clinical outcomes; however, the treatment response had an association with the MRD result (P < 0.05). Modified L-CHOP prolonged median progression-free survival as compared to modified L-COP (215 days vs. 93 days; P < 0.05). Substage b had shorter progression-free survival than substage a (90 days vs. 215 days; P < 0.05). Clinical stage III affected median overall survival time when compared to clinical stages IV and V (432, 173 and 118 days, respectively; P < 0.05). hPARR could be used for screening refractory lymphoma together with lymph node measurement in routine clinical cases.

A FavorAx study of axitinib in favorable risk patients with metastatic renal cell carcinoma.

666 Background: Targeted therapy with axitinib resulted in a greater objective response rate and prolonged progression-free survival (PFS) compared to sorafenib in patients with previously treated metastatic renal cell carcinoma (mRCC) in AXIS study. 75% of patients had intermediate and poor IMDC prognosis. In this phase 2 study, we assessed the activity of axitinib in mRCC patients with favourable risk and a history of prior VEGFR-directed therapy. Methods: Patients were required to have clear cell mRCC, favourable risk according to IMDC criteria, and to have received first-line treatment with sunitinib or pazopanib. Prior treatment with other agents was not permitted. The primary endpoint of the study was PFS. Additional endpoints included response rate, safety, and overall survival (OS). Results: A total of 21 patients were enrolled, 62% of whom were male. Median age was 59 years. 11 (52%) patients had 2 and more metastatic sites. 67% and 33% of patients received first-line sunitinib or pazopanib with a median PFS of 17 months (95% CI 14-20). After a median follow-up of 16 months, the median PFS and OS was not yet reached. The current study did achieve its primary endpoint based on the 10-month PFS of 71.4%. 3 (14.3%) patients had confirmed partial responses and 14 (66.7%) had stable disease. No grade 3/4 treatment-related adverse events were observed; the most frequent grade 1/2 treatment-related adverse events were hypertension (57.1%), fatigue (57.1%), GI (33%) and skin (19%) toxicity. 7 patients had dose-escalation of axitinib and 1 patient had dose reduction. Conclusions: The encouraging PFS and favorable safety profile observed in FavorAx study support the administration of axitinib in mRCC patients with favourable IMDC risk and a history of prior sunitinib or pazopanib. Clinical trial information: NCT02700568.

Abstract P5-21-27: Efficacy and safety of ribociclib plus letrozole in US patients enrolled in the MONALEESA-2 study

Abstract Background: Endocrine-based therapy is the standard of care for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC), in whom delaying disease progression is the primary goal. In the randomized Phase 3 MONALEESA-2 study (ClinicalTrials.gov identifier, NCT01958021), first-line ribociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) + letrozole significantly prolonged progression-free survival (PFS) compared with placebo + letrozole in postmenopausal women with HR+, HER2− ABC (hazard ratio, 0.556; 95% confidence interval [CI], 0.429–0.720) at the interim analysis cutoff date. Here, we present safety and efficacy data from US patients who were enrolled in the MONALEESA-2 study. Methods: Postmenopausal women (N=668) with HR+, HER2− ABC who did not receive prior systemic treatment for ABC and had an Eastern Cooperative Oncology Group performance status score of ≤1, adequate bone marrow and organ function, and no history of active cardiac dysfunction were randomized 1:1 to receive either ribociclib (600 mg/d, 3 weeks on/1 week off) + letrozole (2.5 mg/d, continuous) or placebo + letrozole. The primary end point was locally assessed PFS. The data cutoff for this analysis was January 29, 2016. Results: Baseline demographics, patient disposition, and prior therapy were well balanced across treatment groups in the US subset (N=213; ribociclib group, n=100; placebo group, n=113). Median treatment duration was 16.3 months. In US patients, median PFS was significantly prolonged in the ribociclib group (median PFS, not reached [NR]; 95% CI, 17.1 months to NR) versus the placebo group (median PFS, 14.4 months [95% CI, 11.1–18.4 months]; hazard ratio, 0.451 [95% CI, 0.281–0.724]; P=0.000363), with a median follow-up of 11.0 months. In a subsequent preplanned analysis of overall survival, median PFS was 27.6 months in the ribociclib group versus 15.0 months in the placebo group (hazard ratio, 0.527; 95% CI, 0.351–0.793). The overall response rate (ORR) was significantly greater in the ribociclib group (ORR, 38.0%; 95% CI, 28.5–47.5%) versus the placebo group (ORR, 26.5%; 95% CI, 18.4–34.7%; P=0.040). A trend toward benefit was observed with ribociclib in all subgroups (including age, disease burden, prior therapy, and biomarker status), which was consistent with the overall population. No on-treatment deaths occurred. The most common all-grade adverse events, irrespective of causality, were neutropenia (ribociclib, 69.0%; placebo, 3.7%), nausea (ribociclib, 65.0%; placebo, 39.4%), fatigue (ribociclib, 56.0%; placebo, 46.8%), and diarrhea (ribociclib, 41.0%; placebo, 32.1%). The most common grade 3 (≥25% in either group) and grade 4 (≥10% in either group) AE was neutropenia (grade 3: ribociclib, 39.0%; placebo, 0%; grade 4: ribociclib, 14.0%; placebo, 0%). Two patients (2.0%) in the ribociclib group and none in the placebo group experienced febrile neutropenia. Conclusions: The US patients in the MONALEESA-2 study derived significant PFS benefit from ribociclib + letrozole compared with placebo + letrozole, with a 55% reduction in the relative risk of disease progression. The safety profile was consistent with and comparable to the global study population. Citation Format: Yardley DA, Hart L, Favret A, Blau S, Diab S, Richards D, Sparano J, Beck JT, Richards P, Ward P, Ramaswamy B, Tsai M, Pluard T, Tolaney S, Esteva F, Small T, Purkayastha D, Miller M, Hortobagyi G. Efficacy and safety of ribociclib plus letrozole in US patients enrolled in the MONALEESA-2 study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-27.

Abstract GS2-05: First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial

Abstract Background:Endocrine therapy (ET) with ovarian function suppression is an established first-line treatment for pre- and peri-menopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). Addition of ribociclib (orally bioavailable, selective cyclin-dependent kinase [CDK] 4/6 inhibitor) to first-line ET prolonged progression-free survival (PFS) in a Phase III trial of postmenopausal women with HR+, HER2– ABC (MONALEESA-2). Here we report results from MONALEESA-7 (NCT02278120), the first double-blind, randomized, Phase III trial evaluating ribociclib + tamoxifen/non-steroidal aromatase inhibitor (NSAI) and goserelin specifically in pre- and peri-menopausal patients. Methods: Pre- or peri-menopausal women with HR+, HER2– ABC who had received ≤1 line of chemotherapy and no prior ET for ABC were randomized (1:1) to ribociclib (600 mg/day, 3-weeks-on/1-week-off) or placebo in combination with either tamoxifen (20 mg/day) or an NSAI (letrozole [2.5 mg/day] or anastrozole [1 mg/day]) + goserelin (3.6 mg every 28 days). The primary endpoint was locally assessed PFS. Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), and safety. Results: 672 patients were enrolled. Baseline patient characteristics were balanced between treatment arms. The primary analysis was conducted after 318 events had occurred; median time from randomization to data cut-off date was 19.2 months. The study met its primary objective: PFS was significantly improved in the ribociclib arm (median PFS = 23.8 months; 95% CI: 19.2–not reached) vs the placebo arm (median PFS = 13.0 months; 95% CI: 11.0–16.4), with a hazard ratio of 0.553 (95% CI: 0.441–0.694; p=9.83×10–8). Subgroup analyses demonstrated consistent PFS benefits for ribociclib vs placebo. In patients with measurable disease at baseline, ORR was 51% vs 36% (ribociclib vs placebo arm; p=3.17×10–4) and CBR was 80% vs 67% (p=3.40×10–4). The most frequent all-grade adverse events (Aes; ≥25% of patients; ribociclib vs placebo arm) were neutropenia (76% vs 8%), hot flush (34% vs 34%), nausea (32% vs 20%), leukopenia (31% vs 6%), and arthralgia (30% vs 27%). Of these, neutropenia (61% vs 4%) and leukopenia (14% vs 1%) were the only Grade 3/4 events reported in ≥5% of patients (ribociclib vs placebo arm). Febrile neutropenia (ribociclib vs placebo arm) occurred in 2% vs &amp;lt;1% of patients. Grade 3/4 QT prolongation (ribociclib vs placebo arm) was reported in 1% vs &amp;lt;1% of patients. Aes leading to permanent discontinuation of ribociclib + tamoxifen/NSAI + goserelin vs placebo + tamoxifen/NSAI + goserelin occurred in 4% vs 3% of patients. Conclusions: MONALEESA-7, the first dedicated trial investigating a CDK4/6 inhibitor in pre- and peri-menopausal women with HR+, HER2– ABC, demonstrated that addition of ribociclib to first-line ET (tamoxifen/NSAI + goserelin) significantly prolonged PFS and had a manageable safety profile. The trial validates the clinical utility of ribociclib with multiple endocrine therapies, including tamoxifen, in premenopausal women with HR+, HER2– ABC. Citation Format: Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS2-05.

Abstract P5-20-01: Prolonged progression-free survival (PFS) in advanced HER2+ metastatic breast cancer with or without brain metastases: A pooled analysis of tucatinib phase 1b studies

Abstract Background: Advances in the treatment for HER2+ breast cancer using sequential HER2 targeted therapies has resulted in improvements in outcome. Nonetheless, treatment of HER2+ metastatic breast cancer (MBC) following 1st and 2nd line HER2 targeted therapies is therapeutically challenging. Currently there is no consensus regarding a single standard of care for such patients including those with brain metastases (BM). Tucatinib is a highly selective oral tyrosine kinase HER2 inhibitor that has shown promising results in the treatment of HER2+ MBC in patients both with and without BM. Methods: Two Phase 1b studies of tucatinib were pooled to identify and characterize the subgroup of patients with extended PFS as defined by achieving twice the median PFS observed in the trials. Results: 77 patients treated at the recommended Phase 2 dose (tucatinib 300 mg PO BID) were analyzed, 50 in Study 004 (tucatinib + T-DM1) and 27 in Study 005 (tucatinib +/- trastuzumab +/- capecitabine). Patients received a median of 3 prior therapies including a taxane, trastuzumab, pertuzumab, T-DM1 (Study 005 only), and lapatinib. Median PFS was 8.2 months in Study 004 and 7.8 months in the triplet cohort in Study 005. 15 patients (19.5%) demonstrated PFS &amp;gt;16 months, representing an extended PFS subgroup. Of these patients, 50% had baseline brain metastases, similar to the percentage of all patients entering the trial at baseline. No differences in the incidence of hormone receptor status (positive or negative), presence of visceral metastases, number of prior HER2 regimens, time from diagnosis (initial and metastatic) to study initiation, metastatic disease burden at study entry (LDH, number of target and nontarget lesions, sum of diameters of target lesions) or age were seen when comparing patients with or without extended PFS. Conclusions: Nearly 20% of patients treated with tucatinib combinations for late stage MBC demonstrate prolonged PFS defined as &amp;gt; 16 months, representing a significant subgroup of patients who have extended disease control. Patient characteristics such as hormone receptor status, presence of visceral disease, burden of disease and age did not predict for extended PFS on tucatinib. While the presence of BM has historically negatively impacted PFS in clinical trials, baseline BM did not differentiate patients who achieved extended PFS. Further molecular characterization of the extended PFS cohort could help to identify this patient group. These data, demonstrating a significant subgroup of patients with extended PFS, further support the use of tucatinib in the accruing randomized HER2CLIMB trial. Citation Format: Hamilton E, Murthy R, Ferrario C, Conlin A, Krop I, Falkson C, Khan Q, Chamberlain M, Gray T, Borges V. Prolonged progression-free survival (PFS) in advanced HER2+ metastatic breast cancer with or without brain metastases: A pooled analysis of tucatinib phase 1b studies [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-01.

Abstract P5-21-18: Subsequent treatment for postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer who received ribociclib + letrozole vs placebo + letrozole in the phase III MONALEESA-2 study

Abstract Background: In the Phase III MONALEESA-2 study (NCT01958021), ribociclib (RIB; cyclin-dependent kinase 4/6 inhibitor [CDK4/6i]) + letrozole (LET) significantly prolonged progression-free survival (PFS) vs placebo (PBO) + LET in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). The optimal treatment sequence following first-line CDK4/6i-based therapy is not yet known. Here we report the subsequent therapies received following discontinuation from MONALEESA-2. Methods: The MONALEESA-2 study enrolled 668 patients (pts) with HR+, HER2– ABC. Pts were randomized 1:1 to receive RIB (600 mg/day; 3-weeks-on/1-week-off) + LET (2.5 mg/day; continuous) or PBO + LET. Following discontinuation of MONALEESA-2 study treatment, pts were followed for information regarding post-study treatment, including type and duration of therapy. Results: At data cut-off (January 2, 2017), the median duration of follow-up was 26.4 months. Median PFS was 25.3 vs 16.0 months in the RIB + LET vs PBO + LET arms (hazard ratio=0.568; 95% confidence interval [CI]: 0.457–0.704; p=9.63x10–8). 203 (60.8%) vs 246 (73.7%) pts had discontinued RIB + LET vs PBO + LET. The median time to end of treatment was 20.3 months in the RIB + LET arm vs 13.7 months in the PBO + LET arm. First subsequent antineoplastic treatment was reported for 172/203 (84.7%) vs 212/246 (86.2%) pts who received RIB + LET vs PBO + LET; second subsequent therapy was reported for 45/203 (22.2%) vs 68/246 (27.6%) pts. The median time to first subsequent therapy (from randomization to the first post-study dose of therapy) was 24.2 (95% CI: 20.9–27.6) vs 16.7 (95% CI: 14.8–19.3) months in pts who received RIB + LET vs PBO + LET; median time to initiation of second subsequent therapy was not reached in either arm. The most common type of first subsequent therapy was single-agent hormonal therapy in 90 (44.3%) vs 87 (35.4%) pts who discontinued RIB + LET vs PBO + LET; chemotherapy was the most common second subsequent therapy in 20 (9.9%) vs 36 (14.6%) pts. Chemotherapy alone was the first subsequent treatment after MONALEESA-2 discontinuation in 32 (15.8%) vs 55 (22.4%) pts treated with RIB + LET vs PBO + LET. Conclusions: RIB + LET significantly prolongs PFS and delays the start of subsequent lines of therapy vs PBO + LET in pts with HR+, HER2– ABC. The most common first subsequent therapy following discontinuation of RIB + LET or PBO + LET was single-agent hormonal therapy, and fewer pts treated with RIB + LET received subsequent chemotherapy compared with those who received PBO + LET. Citation Format: Blackwell KL, Paluch-Shimon S, Campone M, Conte P, Petrakova K, Favret A, Blau S, Beck JT, Miller M, Sutradhar S, Monaco M, Burris HA. Subsequent treatment for postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer who received ribociclib + letrozole vs placebo + letrozole in the phase III MONALEESA-2 study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-18.

Abstract OT2-06-02: A randomized phase II study of maintenance hormone therapy with or without capecitabine after induction therapy with bevacizumab plus paclitaxel in hormone receptor positive and HER2 negative metastatic breast cancer (KBCSG-TR1214)

Abstract Background: The combination therapy of Bevacizumab (B) and Paclitaxel (P) has proved to prolong progression free survival (PFS) in E2100 and MERiDiAN study for advanced and metastatic breast cancer(AMBC). Because of its longer PFS, developing optimal therapeutic strategy of B+P to improve survival, including management of toxicity is crucial. From the International Consensus Conference for Advanced Breast Cancer, most experts agreed the maintenance endocrine therapy after effective induction chemotherapy in AMBC. In KBCSG-TR 1214 study, we planned to examine the following clinical questions. 1. As a maintenance therapy, which is more effective either endocrine therapy alone (E) or endocrine therapy with capecitabine (E+C)? 2. Can maintenance therapy reduce toxicity of B+P and restore patient's QOL.? 3. How effective is B+P re-challenge after failure of maintenance therapy? Methods: KBCSG-TR 1214 study is multicenter open-labeled randomized phase II trial for hormone receptor (HR)-positive and HER2-nagative patientswho have experienced none or one prior chemotherapy for AMBC. Patients will receive B (10mg/kg q2w) in combination with P (90mg/m2 on day 1, 8, and 15 q4w) as an induction therapy. Patients without progression after 6 cycles of B+P will be randomized to E or E+C. Endocrine treatment has been administrated by their physician's choice. Patients in E+C will receive endocrine therapy with capecitabine 1657mg/m2 on day1 to 21 q4w. Stratification factors for randomization are menopausal status, presence of target lesion, number of prior endocrine therapies for AMBC, with or without 1st line chemotherapy for AMBC. After progression of maintenance therapy (E or E+C), B+P will be started again as a re-challenge therapy. Primary end point is PFS of maintenance therapy. Secondary end points include time to failure of strategy from randomization, efficacy of re-challenge therapy, overall survival and safety of induction therapy. Translational research is also planned. VEGF, angiopoetin-1, and apelin in plasma will be measured at four points (before induction therapy, at the beginning of the maintenance therapy and the re-induction therapy, and at the end of the trial). The sample size was calculated by typeIerror (1-sided) of 0.05 and 80% power to estimate median PFS of each maintenance therapy 9 months with a threshold of 6 months. The target number of patients enrolled and randomized after induction therapy was 120 and 90, respectively. Enrollment has been completed with 116 patients as of April, 2016 and 90 patients had been successful to shift to the maintenance phase with randomization. The last patient had been randomized on October, 2016. The first analysis will be planned during the second quarter of 2018 (UMIN000008662). Citation Format: Yamaguchi M, Nakayama T, Yoshinami T, Ikeda M, Iwamoto M, Komoike Y, Takashima T, Tsurutani J, Yoshidome K, Yamada T, Morita S, Masuda N. A randomized phase II study of maintenance hormone therapy with or without capecitabine after induction therapy with bevacizumab plus paclitaxel in hormone receptor positive and HER2 negative metastatic breast cancer (KBCSG-TR1214) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-06-02.

Randomized, open label, multicenter, phase II trial comparing transarterial chemoembolization (TACE) plus sorafenib with TACE alone in patients with hepatocellular carcinoma (HCC): TACTICS trial.

206 Background: There is no proven evidence that combination therapy of TACE with sorafenib (TS group) prolong progression-free survival (PFS) and/or overall survival (OS) compared to TACE alone (T group) in patients with unresectable HCC. Methods: In this randomized, open label, multicenter, comparative trial (NCT01217034), patients with unresectable HCC, Child-Pugh score ≤7, ECOG performance status 0-1, no vascular invasion (VI), no extrahepatic spread (EHS), size≤10 cm and number≤10 and adequate organ function were randomized 1:1 (stratification by institution, Milan criteria in or out, and number of previous TACE 0 or 1-2) to T or TS. In TS group, sorafenib 400 mg once daily was pretreated for 2-3 weeks prior to TACE followed by 800mg once daily during on-demand conventional TACE sessions until the time to untreatable progression (TTUP), which was defined as the time to the date of a state when TACE continuation is not possible due to untreatable tumor progression, deterioration to Child-Pugh C or appearance of VI/EHS. Co-primary endpoints are PFS and OS. Multiplicity is adjusted using a gatekeeping hierarchical testing. PFS event in this trial was defined as death or time to TTUP. Key secondary endpoints were time to progression and safety. PFS is expected to 40% extension from 18 months (control arm) to 25 months, target HR was 0.71, with a power of 0.80. Results: The trial was conducted in 33 institutions and a total of 156 patients were randomized to T (n = 76) or TS (n = 80). Median PFS in the T group and TS group was 13.5 and 25.2 months (HR = 0.59, 95%CI 0.41-0.87; p = 0.006), respectively. The number of OS events has not reached. Median TTP was 13.5 and 24.1 months in the T and TS groups (HR = 0.56, 95%CI 0.38-0.83; p = 0.004). Median TTUP was 20.6 and 26.7 months in the T and TS groups (HR = 0.57, 95%CI 0.35-0.92; p = 0.02), respectively. There was no unexpected toxicity. Conclusions: Sorafenib in combination with TACE significantly improved PFS over TACE alone in patients with unresectable HCC. Adverse events were consistent with the known safety profile with previous TACE combination trials. Clinical trial information: NCT01217034.

Relation between irinotecan-induced cholinergic syndrome and prognosis of colorectal cancer patients.

859 Background: It is well known that a cetuximab induced rash is strongly associated with improved survival of colorectal cancer patients. Irinotecan Induced Cholinergic Syndrome (IICS), manifesting in such events as early diarrhea and diaphoresis, is a notorious adverse effect of irinotecan. In this study, we reveal the relation between IICS and prognosis of colorectal cancer patients and examine the validity of IICS as a surrogate marker for the efficacy of irinotecan. Methods: We retrospectively reviewed data from 52 colorectal cancer patients who were treated with a chemotherapeutic regimen that included irinotecan at Kure Medical Center between 2012 and 2017. First, to assess the relation between adverse events and efficacy of irinotecan, patients who experienced IICS (n = 11) and did not experience IICS (n = 41) were analyzed from the aspect of overall survival (OS), progression-free survival (PFS), sex, age, dose, performance status (PS) and previous chemotherapy (PC). Kaplan-Meier survival curves were drawn for OS and PFS, and compared by means of a log-rank test. Secondly, to determine the response rate of butylscopolamine for IICS, we injected butylscopolamine 20mg into the irinotecan infusion bag and administered both agents through the intravenous line together to 11 patients who experienced IICS. Results: The presence of IICS was associated with a prolonged median OS (589 vs. 280 days, log-rank p = 0.0282; adjusted hazard ratio (HR) 0.27, 95% confidence interval [CI] 0.06-0.79, p = 0.0140), and prolonged median PFS (317 vs. 154 days, log-rank p = 0.1474; adjusted HR 0.56, 95% CI 0.22-1.25, p = 0.1635). There was no statistically significant difference between the two groups in terms of sex, age, dose, PS and PC. Ten patients of 11 patients who were administered butylscopolamine, experienced complete or partial improvement of IICS. The response rate was nearly 90%. Conclusions: The presence of IICS is associated with an improved OS for colorectal cancer patients and tends to have a positive correlation with PFS. IICS is a viable surrogate biomarker of the antitumor efficacy of irinotecan. As a prophylaxis of IICS, mixing butylscopolamine into the irinotecan infusion bag was remarkably effective.

Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response

Background:Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent.Methods:Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) by receiver operating characteristic (ROC) analysis and logistic regression) for prediction of benefit (PFS) from sunitinib.Results:Data for 237 patients (85 placebo; 152 sunitinib (n=66.50 mg ‘4-weeks on/2-weeks off’ schedule; n=86 ‘37.5 mg continuous daily dosing (CDD)’)) and 788 scans were analysed. The median PFS for sunitinib and placebo were 9.3 months (95% CI 7.6–12.2) and 5.4 months (95% CI 3.5–6.01), respectively (hazard ratio (HR) 0.43 (95% CI 0.29–0.62); P<0.001). A PR was seen in 19 patients (13%) on sunitinib; the median change in the sum of the lesions (vs baseline) was −12.8% (range −100 to +36.4). Month 7 was the most informative time-point (AUC 0.78 (95% CI 0.66–0.9); odds ratio 1.05 (95% CI 1.01–1.08), P=0.002). Reduction of 10% (vs baseline) achieved the highest sensitivity (50%) and specificity (82%), amongst cut-offs tested. A 10% reduction in marker lesions was associated with improved PFS in the whole sunitinib population (HR 0.55 (95 CI 0.3–0.9); P=0.04); mostly in patients on sunitinib CDD (HR 0.33 (95% CI 0.2–0.7); P=0.005). A 10% reduction in marker lesions (P=0.034) and sunitinib treatment (P=0.012) independently impacted on PFS (multivariable analysis).Conclusions:A 10% reduction within marker lesions identifies pNET patients benefiting from sunitinib treatment with implications for maintenance of dose intensity and future trial design.

Outcomes and Treatment Patterns in Patients with Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Diagnosed at Craniotomy: A Single Institution Study

NSCLC remains the largest cause of cancer death in the US and more than two-thirds of patients have either locally advanced or metastatic disease at diagnosis, including a large subset who present with symptomatic intracranial metastases. Historically, such patients had a uniformly poor prognosis, but in recent years, those with oligometastatic disease are increasingly being evaluated for thoracic consolidative radiation therapy (T-RT) due to the improvement in systemic therapies and prolonged progression-free survival (PFS). We retrospectively reviewed a cohort of patients with NSCLC who were diagnosed at craniotomy to establish a pathologic diagnosis and palliate symptoms. We assessed the types of treatments offered, PFS, overall survival (OS), and factors influencing outcome. A neurosurgical database of patients undergoing craniotomy in 2014-2015 was filtered to include those diagnosed with NSCLC at the time of that surgery and underwent further treatment at our institution. Medical records were reviewed for demographics, descriptors of the intracranial and extracranial burden of disease, systemic therapies, radiation therapy courses, PFS, and OS. Descriptive statistics were computed and 95% confidence intervals (CI) were constructed for Kaplan-Meier median survival estimates. Summary statistics were computed for factors associated with receipt of T-RT. Of 104 patients identified, 67 patients met inclusion criteria with available clinical information. Median age at time of presentation was 64 (range: 28-92). Median KPS was 80. Median number of brain metastases was 2 (range: 1-24), with a median volume of largest brain metastasis of 19cc (range: 1-75). WBRT was utilized for 38 patients (56.7%), while 28 (41.8%) had radiosurgery to the craniotomy cavity and other sites of intracranial disease. Two patients (3.8%) went straight to systemic therapy. Consolidative T-RT was used in 28 patients (41.8%); criteria for T-RT use were not pre-specified. Median PFS in patients who did and did not receive T-RT was 8.0 and 2.3 months, respectively (p<0.01). Median OS in patients who did and did not receive T-RT was 17.9 months and 4.3 months, respectively (p<0.01). Factors associated with T-RT receipt included higher KPS (p<0.01) and receipt of SRS for brain lesions (p=0.03). Patients presenting with intracranial metastases from NSCLC who are candidates for craniotomy appear to have prolonged OS as compared to historical benchmarks. In our cohort, consolidation T-RT was associated with prolonged survival. Although assignment of patients to T-RT in this retrospective cohort was not based on pre-specified criteria and might have been related to unknown bias, the hypothesis that T-RT improves OS in patients with oligometastatic disease should be further tested in prospective clinical trials.

Isolated limb perfusion for locally advanced angiosarcoma in extremities: A multi-centre study

BackgroundAngiosarcomas are rare and aggressive soft-tissue sarcomas. The only potential curative treatment is complete surgical excision. This study reports the outcome of isolated limb perfusion (ILP) with high-dose melphalan and tumour necrosis factor α for locally advanced angiosarcoma. Material and methodsAll patients who underwent an ILP for angiosarcomas between 1991 and 2016 in three tertiary referral centres were identified from prospectively maintained databases. ResultsA total of 39 patients were included, with a median follow-up of 18 months (interquartile range 6.1–60.8). Of these patients, 23 (58.9%) patients had a complete response (CR) after ILP, 10 (25.6%) had a partial response, 4 (10.3%) had stable disease and 2 (5.1%) patients had progressive disease immediately after ILP. A total of 22 patients developed local progression (56.4%), whereas nine (23.1%) developed distant metastases. The patients with CR had a significantly prolonged median local progression-free survival (PFS) (15.4 versus 7.3 months, p = 0.015) when compared with non-CR patients, and a trend towards better median overall survival (81.2 versus 14.5 months, p = 0.054). Six patients underwent multiple ILPs, whereby the CR rate of the first, second and third ILPs were 60%, 80% and 67%, respectively. Thirteen (33.3%) patients needed further surgical intervention, consisting of resection in eight patients (20.5%) and amputation in five patients (12.8%). ConclusionILP is an effective treatment option for patients with locally advanced angiosarcoma in the extremities, resulting in a high number of CRs, a high limb salvage rate and prolonged local PFS.

Model-based meta-analysis of progression-free survival in non-Hodgkin lymphoma patients.

Non-Hodgkin lymphoma (NHL) is a group of lymphoproliferative malignancies with varying treatment responses and progression-free survival (PFS) times. The objective of this study was to quantify the effect of treatment and patient-population characteristics on PFS in patients with NHL. A database was developed from 513 NHL clinical trials reported from 1993 to 2015. Summary-level PFS was obtained from 112 of these trials, which included 155 cohorts and 11,824 patients. Characteristics evaluated for their impact on PFS included cohort treatment, percentage of patients with each NHL subtype, percentage of patients with different numbers of prior treatments, percentage of subjects previously administered rituximab, performance status, disease stage, median age, and sex distribution. Rituximab, bendamustine, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone combination)/CHOP-like, and other nonchemotherapy drugs, aside from bortezomib, prolonged median PFS time 2 to 4-fold. Follicular lymphoma patients had 60% longer median PFS time than mantle cell lymphoma (MCL) patients, while diffuse large B-cell lymphoma patients had a median PFS time that was 25% of MCL patients. Patients who received ≤1 prior treatment had median PFS times > 10-fold longer than patients who received ≥2 prior treatments. The final model predicted the hazard ratio in 75% of the studies within 25% of the observed value and the observed median PFS time of 92% of the studies fell within the predicted 90% confidence intervals. The developed PFS model predicts the median PFS time and hazard ratio for specific populations and treatment combinations quantitatively and can potentially be extended to link short-term and long-term clinical outcomes.

Randomized phase IIB evaluation of weekly paclitaxel versus weekly paclitaxel with oncolytic reovirus (Reolysin®) in recurrent ovarian, tubal, or peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study

ObjectiveTo assess whether the addition of oncolytic reovirus (Reolysin®) to weekly paclitaxel prolonged progression-free survival (PFS) in the treatment of women with recurrent or persistent ovarian, tubal or primary peritoneal cancer. Patients and methodsPatients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to paclitaxel (80mg/m2 intravenously days 1, 8, and 15 every 4weeks) or the combination of paclitaxel (80mg/m2 intravenously days 1, 8, and 15) plus reovirus 3×1010TCID50/day intravenously on days 1–5, both every 4weeks until disease progression or toxicity. The primary end point was PFS. The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%. ResultsThe study accrued 108 patients, 100 of whom were evaluable for toxicity. Median PFS was 4.3months for paclitaxel and 4.4months for paclitaxel plus reovirus (hazard ratio, 1.11; 90% two-sided CI, 0.78 to 1.59; one-sided P=0.687). The proportion responding (overall response rate) to paclitaxel was 20% among 45 patients with measurable disease receiving paclitaxel alone, and 17.4% among the 46 patients treated with the combination. The asymptotic relative probability of responding was 0.87 (90% CI, 0.42 to 1.79). Severe adverse events were more common in the combination regimen than in paclitaxel arm for severe neutropenia (grade≥4, 12% versus 0%), and severe respiratory adverse events (grade≥3, 25% versus 2%). No deaths were considered treatment related. ConclusionThe addition of reovirus to weekly paclitaxel in the treatment of women with recurrent or persistent ovarian, tubal or peritoneal cancer did not sufficiently reduce the hazard of progression or death to warrant further investigation.

Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis.

Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting. Patients and Methods The meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Myélome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for primary efficacy analysis. Results Overall, 1,208 patients were included in the meta-analysis (605 patients in the lenalidomide maintenance group and 603 in the placebo or observation group). The median PFS was 52.8 months for the lenalidomide group and 23.5 months for the placebo or observation group (hazard ratio, 0.48; 95% CI, 0.41 to 0.55). At a median follow-up time of 79.5 months for all surviving patients, the median OS had not been reached for the lenalidomide maintenance group, whereas it was 86.0 months for the placebo or observation group (hazard ratio, 0.75; 95% CI, 0.63 to 0.90; P = .001). The cumulative incidence rate of a second primary malignancy before disease progression was higher with lenalidomide maintenance versus placebo or observation, whereas the cumulative incidence rates of progression, death, or death as a result of myeloma were all higher with placebo or observation versus lenalidomide maintenance. Conclusion This meta-analysis demonstrates a significant OS benefit and confirms the PFS benefit with lenalidomide maintenance after ASCT in patients with NDMM when compared with placebo or observation.

Abstract CT010: Efficacy results based on PIK3CA status in BELLE-3: A Phase 3 study of buparlisib (BKM120) + fulvestrant in postmenopausal women with aromatase inhibitor-treated, HR+/HER2- ABC after progression on an mTOR inhibitor

Abstract Introduction The phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is often activated in endocrine therapy (ET)-resistant, hormone receptor-positive (HR+) breast cancer (BC). Adding a PI3K inhibitor (PI3Ki) to ET may overcome ET or mTOR inhibitor (mTORi) resistance. In the Phase 3 BELLE-2 study, the pan-PI3Ki buparlisib (BUP) + fulvestrant (FULV) prolonged progression-free survival (PFS) in patients (pts) with HR+, human epidermal growth factor receptor 2-negative (HER2–) advanced BC (ABC), particularly in pts with PIK3CA mutations in circulating tumor DNA (ctDNA). Here, we report biomarker results from BELLE-3 (NCT01633060). Methods In total, 432 postmenopausal women with HR+/HER2– ABC who previously received an aromatase inhibitor and progressed on/within 30 days of ET + mTORi treatment were enrolled. Pts must not have received &amp;gt;1 chemotherapy regimen for ABC, or any prior PI3Ki, protein kinase B (AKT) inhibitor, or FULV. Pts were randomized 2:1 to receive BUP (100 mg/day) + FULV (500 mg) or placebo (PBO) + FULV, stratified by visceral disease status. PIK3CA status was assessed by BEAMing (exons 9 and 20 only) in plasma ctDNA collected at baseline, and in archival tumor samples by polymerase chain reaction (PCR) and next-generation sequencing (NGS). The primary endpoint was locally assessed PFS (RECIST v1.1). Secondary endpoints included overall survival, overall response rate, PFS by ctDNA PIK3CA status, quality of life, and safety; with exploratory PFS analyses by PIK3CA status in tumor tissue. Results BELLE-3 met its primary objective: PFS was significantly prolonged for BUP vs PBO, with hazard ratio (HR) 0.67 (95% confidence interval [CI]: 0.53–0.84; p&amp;lt;0.001) and median PFS 3.9 vs 1.8 months. PIK3CA mutations were present in 135/348 (39%) available ctDNA samples, 109/321 (34%) tumor samples (by PCR), and 76/185 (41%) tumor samples (by NGS). PFS benefit for BUP vs PBO was higher in the PIK3CA-mutant ctDNA group (HR 0.46 [95% CI: 0.29–0.73]; median PFS 4.2 vs 1.6 months) than the PIK3CA-wild-type (WT) group (HR 0.73 [95% CI: 0.53–1.00]; median PFS 3.9 vs 2.7 months). PFS benefit was also higher in the PIK3CA-mutant tumor tissue group by PCR (HR 0.39 [95% CI: 0.23–0.65]) than the PIK3CA-WT group (HR 0.83 [95% CI: 0.60–1.14]), and in the PIK3CA-mutant tumor tissue group by NGS (HR 0.46 [95% CI: 0.26–0.82]) than the PIK3CA-WT group (HR 0.62 [95% CI: 0.40–0.97]). PIK3CA status in ctDNA and archival tissue by PCR had an overall concordance of 83%, with a sensitivity of 79% and specificity of 85%. Conclusions BELLE-3 met its primary endpoint in the full population. PFS benefit for BUP vs PBO was higher in pts with PIK3CA mutations detected in ctDNA or archival tissue (by PCR or NGS). Ongoing Phase 3 studies with PI3Kα-selective inhibitors will confirm the predictive value of PIK3CA mutations in ctDNA and tumor tissue on efficacy. Citation Format: Ruth O'Regan, Carlos L. Arteaga, Thomas Bachelot, Eva Ciruelos, Per E. Lønning, Banu Sankaran, Ying A. Wang, Nicolas Scheuer, Dalila Sellami, Samit Hirawat, Angelo Di Leo. Efficacy results based on PIK3CA status in BELLE-3: A Phase 3 study of buparlisib (BKM120) + fulvestrant in postmenopausal women with aromatase inhibitor-treated, HR+/HER2- ABC after progression on an mTOR inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT010. doi:10.1158/1538-7445.AM2017-CT010