tbuckley/cabot-search huggingface dataset:
Impact of overall severity of adverse events (AEs) on long-term outcomes in metastatic colorectal cancer (mCRC) patients (pts) treated with first line systemic chemotherapy: Findings from 3,971 pts in the ARCAD database.
Authors: John Raymond Zalcberg, Qian Shi, Danielle Angela Ferraro, Jeffrey P. Meyers, Leonard Saltz, Richard Goldberg, Eric Van Cutsem, Herbert Hurwitz, Charles Fuchs, Carsten Bokemeyer, Daniel J. Sargent, Aimery De Gramont, Timothy Jay Price, Richard Adams
Journal: Journal of Clinical Oncology (2017)

3582 Background: The prognostic importance of the incidence, severity, type and duration of AEs pts experience during chemotherapy varies between tumor types, and the available evidence across the board is often conflicting. Here we investigated the impact of the overall severity of AEs among pts with mCRC receiving first-line oxaliplatin (Oxa)- and/or irinotecan(Iri)-based regimens. Methods: The overall severity of AE data (i.e., max grade (G) of all AEs) were available on 3,971 pts (median age 61; 60% male, 47% ECOG PS 1+; 57% 2+ metastatic sites) enrolled onto 6 1 st -line randomized trials. Around 46%, 45%, and 9% of pts had received Oxa-, Iri-, and Oxa+Iri-based regimens, respectively. Pts receiving biologic agents were excluded. Stratified multivariate Cox models were used to assess the associations with overall survival (OS) and progression-free survival (PFS); adjusted hazard ratios (HR adj ) and 95% confidence intervals (CIs) are reported. Results: Pts who only received Oxa-based treatment reported the lowest rate of G3+ AEs (p &lt; .0001) compared to pts treated with Iri- or Oxa+Iri-based regimens. Older age, female gender, and PS 1 or 2+ were associated with higher grade AEs (all p &lt; .0001). Considering AEs experienced within 6w after randomization, 10% and 61% of pts experienced G4+ and G2-3 AEs, respectively. G3+ AEs were associated with a shorter OS for both pts receiving Oxa- (HR adj = 1.2, 95% CI, 1.1-1.3, p adj &lt; .0001) and Iri-based regimens (HR adj = 1.4, 95% CI, 1.2-1.5, p adj &lt; .0001). For the entire treatment course, 19% and 72% of pts experienced G4+ and G2-3 AEs, respectively. For Oxa-based regimens, pts with G3+ AEs had a longer OS (HR adj = 0.86, 95% CI, 0.78-0.94, p adj = .0016), whereas G3+ AEs were associated with a shorter OS (HR adj = 1.2, 95% CI, 1.1-1.4, p adj = .0004) for pts treated with Iri-based regimens. Similar patterns were seen for PFS. Conclusions: Pts who reported higher grade AEs during initial treatment (≤6w) have significantly worse outcome than those who do not. Further analyses with treatment exposure/detailed dose-AE profile and its impact on survival are warranted.
Blood measurements of neuroendocrine tumor (NET) transcripts and gene cluster analysis to predict efficacy of peptide radioreceptor therapy.
Authors: Lisa Bodei, Mark S. Kidd, Wouter A van der Zwan, Ignat Drozdov, Richard P. Baum, Dik J. Kwekkeboom, Eric Krenning, Irvin Mark Modlin
Journal: Journal of Clinical Oncology (2017)

4091 Background: Peptide receptor radionuclide therapy (PRRT) capitalizes on somatostatin receptor (SSR) overexpression on NETs to deliver targeted isotope therapy. Objective prediction of efficacy remains to be established. Functional imaging of SSR expression (SRE) is used as a predictor of efficacy. Biomarkers e.g. circulating CgA, are ineffective. Circulating NET transcript analysis (NETest) integrated with tumor grade provides a Predictive Quotient Index (PQI) of PRRT. We validated the utility of this PRRT complementary diagnostic in a prospective, blinded study. Methods: 177 Lu-PRRT (29.1±2.2 GBq). NETs ( n= 35); with progressive disease (66%). Baseline evaluations: Clinical status, Grade (Ki67), SRE, CgA (NeoLisa, ULN &gt; 108ng/ml), and NETest (qRT-PCR - multianalyte algorithmic analyses, ULN &gt; 14%). PQI: “omic” NETest gene expression (regulating metabolism and growth factor signaling) mathematically combined with Ki67 index. PQI has two prediction outputs: “responder” (R) vs “non-responder” (NR). Disease control was by RECIST criteria (R vs NR). All samples were blinded. Statistics: Cox proportional multiple regression, Kaplan-Meier survival, &amp; McNemar-test. Results: At restaging, the overall response (disease control rate) was 77%; median PFS not reached (follow-up 4-13 months). Histology: GI: 5; GII: 21; GIII 1; and lung: TC: 2; AC: 5. SRE was Grade 3 (80%). Baseline CgA was 1556±1454ng/ml (89% elevated) and NETest was 60±21% (100% elevated) respectively. Predictive accuracies of SRE, clinical status, CgA levels ( &gt; 2ULN) and NETest ranged from 25-54% (not-significant). PQI was the only predictive marker by multivariate analysis ( p= 0.002). The PQI diagnostic was 92% concordant with outcome and significantly more accurate than all other markers (McNemar: p&lt; 0.002). Cox-proportional modeling confirmed PQI utility (OR: 9.1, p&lt; 0.004). K-MS analysis identified significantly different mPFS between R (not reached) and NR (9.3 months; HR: 8.3, p&lt; 0.0005). Conclusions: A pre-PRRT analysis of circulating NET genes, the predictive quotient index comprising “omic” analysis and grading, is validated to predict the efficacy of PRRT therapy in GEP and lung NETs.
Antitumor activity, safety and predictive biomarker results of ENMD-2076 administered to patients (pts) with recurrent ovarian clear cell carcinoma (OCCC): A trial of the Princess Margaret Phase II Consortium.
Authors: Victor Rodriguez Freixinos, Julia Burnier, Stephanie Lheureux, Blaise Clarke, Anna Tinker, Prafull Ghatage, Neesha Dhani, Marcus Butler, Helen Mackay, Stephen Welch, Johanne Ingrid Weberpals, Katia Sonia Tonkin, Kelly Brooks, Janelle Ramsahai, Lisa Wang, Patricia Ann Shaw, Amit M. Oza
Journal: Journal of Clinical Oncology (2016)

5564 Background: Approximately 50% of OCCC are characterized by inactivating mutations in ARID1A and upregulation of PIK3/AKT/mTOR pathway. ENMD-2076, an anti-angiogenic/anti-proliferative kinase inhibitor has activity against the mitotic kinase Aurora A and showed 6-month (m) progression free survival (PFS) rate of 22% in platinum resistant ovarian cancer (PMID 229211559). Methods: This is a multi-center, open-label, Phase II study of ENMD-2706 (275 mg daily, 28-day cycle) in pts with recurrent OCCC, ECOG ≤ 2, measurable disease and prior platinum therapy. Primary objectives were overall response rate (ORR) and 6-m PFS rate. ARID1A and PTEN expression by immunohistochemistry (IHC) were correlated with outcomes. Results: 32 pts have been enrolled with median follow-up of 4.9 m (range 1.2-24.4), median age 53 years (39–78); 23 pts (71%) had ECOG ≤ 1 and 12 pts (37.5%) received ≥ 1 prior systemic therapy. Among 26 evaluable pts, 19 (73%) had stable disease (SD) and 17 (65%) had median tumor reduction of -13% (-40% to -1%), however objective responses by RECIST 1.1 were not seen. Median PFS is 3.9m (95%CI: 1.8-5.1) and 6m PFS was 23% (95%CI: 9-41). 18 pts had pretreatment biopsy. PTEN and ARID1A expression in 24 archival samples was 41.6% and 45.8% respectively but did not correlate with response (SD vs PD). However, pts with ARID1A loss remained progression free and on therapy for a significantly longer duration (ARID1A loss vs positive, 7.27 m vs. 2.55 m; p < 0.028). DNA sequencing for PI3KCA, ARID1A and PTEN mutations is ongoing. Drug-related adverse events (AEs) occurred in 24/28 (86%) evaluable pts, the most common being Grade (Gr) 1/2 fatigue, nausea/vomiting, hypertension and diarrhea. Gr ≥ 3 AEs were reported in 46% of pts. AE resulted in dose reductions in 11 pts (39%) and led to treatment discontinuation in 3. Conclusions: ENMD-2076 shows activity in OCCC, is generally well tolerated with a side effect profile typical of this class of agent. Predictive value of loss of ARID1A expression and benefit from ENMD-2076 merits further investigation and prospective validation. Clinical trial information: NCT01914510.
Phase I trial of olaparib (PARP inhibitor) and vistusertib (mTORC1/2 inhibitor) in recurrent endometrial, ovarian and triple negative breast cancer.
Authors: Shannon Neville Westin, Jennifer Keating Litton, Rochelle A Williams, Christopher J. Shepherd, Wolfram Brugger, Elizabeth J. Pease, Pamela T. Soliman, Michael M. Frumovitz, Charles F. Levenback, Anil Sood, Larissa Meyer, Stacy L. Moulder, Vicente Valero, Sadia Saleem, Anna Marie Rodriguez, Annies Cyriac, Laverne Engerman, Christine Samuel, Gordon B. Mills, Robert L. Coleman
Journal: Journal of Clinical Oncology (2018)

5504 Background: We sought to determine the recommended phase II dose (RP2D) of olaparib (O) and vistusertib (V) and evaluate molecular markers of response. Methods:Two oral schedules for V were explored with O tablet BID. Arm 1: BID continuous (5 dose levels (DL)) and Arm 2: BID 2 days on/5 days off (4 DL). Clinical benefit rate (CBR) was defined as objective response or stable disease ≥ 6 cycles by RECIST 1.1. Patients (pts) were evaluable for response if they received at least 1 cycle (28 days). An expansion phase (n = 30) was performed at RP2D of Arm 2 with biopsies at baseline and 28 days. Results: 74 pts were enrolled, 8 with BRCA mutation (11%). Median prior therapies was 4 (1-8). There were 2 DLTs on Arm 1 at DL 5 (O 300mg/V 50mg; G4 thrombocytopenia, G3 allergic reaction). There were 3 DLTs on Arm 2. 2 DLTs at DL 1 (O 100mg/V 125mg; G3 neutropenia > 7 days (n = 1); G3 hyperglycemia (n = 1)) and 1 DLT at DL1b (O 200mg/V 100mg; G3 fatigue). RP2D of Arm 1 was O 200mg/V 50mg. RP2D of Arm 2 was O 300mg/V 100mg. Most common adverse events (≥20%) were nausea (84%, G3/4 4%), anemia (83%, G3/4 15%), hyperglycemia (76%, G3/4 3%), fatigue (73%, G3/4 11%), leukopenia (55%, G3/4 9%), increased creatinine (50%, G3/4 0%), headache (42%, G3/4 0%), vomiting (41%, G3/4 5%), hypercholesterolemia (41%, G3/4 0%), diarrhea (39%, G3/4 0%), hypertriglyceridemia (38%, G3/4 1%), thrombocytopenia (38%, G3/4 14%), mucositis (28%, G3/4 4%), transaminitis (28%, G3/4 1%), constipation (28%, G3/4 1%), and pain (28%, G3/4 1%). Of 64 evaluable pts, response rate (RR) across all DL was 19% with median duration 14 mo (4-34). CBR was 34%. RR was 27%, 20%, and 6% for endometrial, ovarian, and breast cancer, respectively. Among 49 evaluable pts treated on Arm 2, RR was 19% and CBR 37%. In Arm 2, RR was 31%, 15%, and 8% for endometrial, ovarian and breast cancer, respectively. Among 6 endometrial cancer responders (3 endometrioid, 3 serous), PI3K pathway, ARID1A, or FBXW7 mutations were common (67%). Conclusions: The combination of olaparib and vistusertib is well tolerated with durable anti-tumor activity. Promising response was seen in both histologies of endometrial cancer. Assessment of molecular correlatives of response will be presented. Clinical trial information: NCT02208375.
The prognostic impact of consensus molecular subtypes (CMS) and its predictive effects for bevacizumab benefit in metastatic colorectal cancer: molecular analysis of the AGITG MAX clinical trial
Authors: J.K. Mooi, P. Wirapati, R. Asher, C.K. Lee, P. Savas, T.J. Price, A. Townsend, J. Hardingham, D. Buchanan, D. Williams, S. Tejpar, J.M. Mariadason, N.C. Tebbutt
Journal: Annals of Oncology (2018)

BackgroundThe consensus molecular subtypes (CMS) is a transcriptome-based classification of colorectal cancer (CRC) initially described in early-stage cohorts, but the associations of CMS with treatment outcomes in the metastatic setting are yet to be established. This study aimed to evaluate the prognostic impact of CMS classification and its predictive effects for bevacizumab benefit in metastatic CRC by correlative analysis of the AGITG MAX trial.Patients and methodsThe MAX trial previously reported improved progression-free survival (PFS) for the addition of bevacizumab (B) to chemotherapy [capecitabine (C)±mitomycin (M)]. Archival primary tumours from 237 patients (50% of trial population) underwent gene expression profiling and classification into CMS groups. CMS groups were correlated to PFS and overall survival (OS). The interaction of CMS with treatment was assessed by proportional hazards model.ResultsThe distribution of CMS in MAX were CMS1 18%, CMS2 47%, CMS3 12%, CMS4 23%. CMS1 was the predominant subtype in right-sided primary tumours, while CMS2 was the predominant subtype in left-sided. CMS was prognostic of OS (P = 0.008), with CMS2 associated with the best outcome and CMS1 the worst. CMS remained an independent prognostic factor in a multivariate analysis. There was a significant interaction between CMS and treatment (P-interaction = 0.03), for PFS, with hazard ratios (95% CI) for CB+CBM versus C arms in CMS1, 2, 3 and 4: 0.83 (0.43–1.62), 0.50 (0.33–0.76), 0.31 (0.13–0.75) and 1.24 (0.68–2.25), respectively.ConclusionsThis exploratory study found that CMS stratified OS outcomes in metastatic CRC regardless of first-line treatment, with prognostic effects of CMS groups distinct from those previously reported in early-stage cohorts. In CMS associations with treatment, CMS2 and possibly CMS3 tumours may preferentially benefit from the addition of bevacizumab to first-line capecitabine-based chemotherapy, compared with other CMS groups. Validation of these findings in additional cohorts is warranted.Clinical trial numberThis is a molecular sub-study of MAX clinical trial (NCT00294359).
<i>GALNT14</i> genotype-guided, sorafenib in combination with transarterial chemoembolization in hepatocellular carcinoma: An interim report of a prospective randomized controlled trial.
Authors: Chau-Ting Yeh, Wei-Chen Lee, Shi-Ming Lin, Chih-Lang Lin, Chao-Wei Hsu, Ting-Jung Wu, Ming-Chin Yu, Chien-Fu Hung, Jeng-Hwei Tseng, Chen-Chun Lin, Wei-Ting Chen, Wei Teng, Yi-Cheng Chen, Ming-Ling Chang
Journal: Journal of Clinical Oncology (2017)

e15657 Background: Sorafenib is the only approved targeted agent for treatment of unresectable hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is the mainstay of treatment for advanced HCC patients in Barcelona Clinical Liver Cancer (BCLC) stage B. Previous randomized controlled trials did not show definite beneficial effect for TACE + sorafenib combination therapy in Asian HCC patients. Recently, an SNP marker on GALNT14gene, rs9679162, was found associated with therapeutic outcomes in HCC patients receiving chemotherapy or chemoembolization, wherein rs9679162-TT genotype was associated with a favorable therapeutic response. In this study, we examined whether this marker could be used as a guide for TACE + sorafenib therapy. Methods: From 2015-Aug, HCC patients in BCLC stage B were genotyped for GALNT14-rs9679162. Patients with genotype TT were treated with TACE alone. Patients with non-TT (CT or CC) were randomized 1:1 to receive TACE + sorafenib treatment or TACE treatment alone (NCT02504983). Results: Interim analysis was performed on 2017-Jan. Totally 40 patients were enrolled. Of them, 16 and 24 patients had GALNT14-TT and non-TT genotypes, respectively. Of the non-TT patients, 11 and 13 patients were randomized into TACE alone (TACEA) and TACE + sorafenib (TACE+S) group. TACEA patients had significant shorter time-to-tumor progression compared with TACE+S (P = 0.019) and GALNT14-TT patients (P &lt; 0.001). No significant difference was found for time-to-therapeutic response (CR + PR) between the three groups. However, when evaluating the time-to-therapeutic response occurring &gt; 3 m of the first TACE (excluding early response), it was found that TACEA patients had significant longer time-to-therapeutic response compared with TACE+S (P = 0.046) and GALNT14-TT patients (P = 0.034). Conclusions: The interim analysis confirmed that patients with GALNT14-TT genotype had a favorable TACE response compared with the non-TT genotype. In addition, in patients with non-TT genotype, TACE + sorafenib combination therapy had a significantly better therapeutic response compared with TACE alone. Clinical trial information: NCT02504983.
The role of Ki-67 in determining optimal chemotherapy in high grade neuroendocrine tumors.
Authors: Katharine Thomas, Brianne Voros, Dipen Chandrakant Patel, J Philip Boudreaux, Ramcharan Thiagarajan, Eugene Woltering, Robert A. Ramirez
Journal: Journal of Clinical Oncology (2018)

4100 Background: High grade (HG) neuroendocrine tumors (NETs) are rare neoplasms with limited data about optimal treatment. This retrospective analysis was performed to determine the most efficacious chemotherapy regimen in HGNETs. Methods: A single center, retrospective review of patients (pts) who received at least one chemotherapy regimen for HGNET between June 1, 2012 and June 1, 2017 was conducted. Data collection included demographics, pathologic characteristics, imaging results and treatment data. Progression free survival (PFS) was defined as date from initial chemotherapy until date of disease progression based on imaging or death. Median overall survival (mOS) was also analyzed. Chemotherapy regimens included combination capecitabine and temozolomide (CAPTEM), platinum-based therapy (cisplatin or carboplatin) or other (fluorouracil, or capecitabine based chemotherapy). Response to treatment was evaluated using RECIST 1.1. Subset analysis was performed based on Ki-67 ( < 55% or ≥55%). Results: Fifty-five pts received chemotherapy. Median number of treatment for those with a Ki-67 of < 55% and ≥55% was 3 and 1, respectively. MOS was 18 months irrespective of chemotherapy regimen; mOS by Ki-67 was 40 months for Ki-67 < 55% versus 16 months for Ki-67 ≥ 55% (Logrank test p = 0.0016). Among all pts undergoing first line therapy, CAPTEM significantly improved PFS (p = 0.041). In a sub analysis, Ki-67 < 55 had a longer PFS with CAPTEM (12-mo), followed by other (7-mo) and platinum (4-mo). In pts with Ki-67 ≥ 55%, PFS was highest in platinum-based therapy (5-mo), followed by CAPTEM (2-mo) and other (1-mo). Kaplan-Meier 3- and 6-month PFS rates based on chemotherapy regimen for pts with Ki-67 < 55% and Ki-67 ≥55 are shown in the table. Conclusions: This study demonstrates optimal first line chemotherapy treatment is dependent on Ki-67. Pts with a Ki-67 < 55 and Ki-67 ≥55 have improved PFS with CAPTEM and platinum-based therapy, respectively. Ki-67 values should be considered when determining first line chemotherapy regimen among pts with HGNET. 1st Line Regimen N Median PFS (mo) 3-mo PFS rate by Ki-67 (%) 6-mo PFS rate by Ki-67 (%) < 55% ≥55% < 55% ≥55% CAPTEM 15 12 77 50 77 50 Other 5 7 67 50 67 50 Platinum-based 35 4 51 58 25 36 Overall 55 5 65 57 54 38
Pembrolizumab (pembro) in combination with dabrafenib (D) and trametinib (T) for <i>BRAF</i>-mutant advanced melanoma: Phase 1 KEYNOTE-022 study.
Authors: Antoni Ribas, F. Stephen Hodi, Donald P. Lawrence, Victoria Atkinson, Alexander Starodub, Matteo S. Carlino, Rosalie Anne Fisher, Georgina V. Long, Wilson H Miller, Yingjie Huang, Scott J. Diede, Scot Ebbinghaus, Omid Hamid
Journal: Journal of Clinical Oncology (2016)

3014 Background: The anti–PD-1 antibody pembro has demonstrated durable responses in ~30%-40% of patients (pts) with advanced melanoma. The combination of BRAF inhibitor D and MEK inhibitor T, the standard treatment for BRAF-mutant melanoma, leads to rapid responses and improved survival, but 50% of pts eventually experience disease progression around 12 mo. KEYNOTE-022 (NCT02130466) is a phase 1/2 study designed to assess safety and efficacy of the recommended doses of pembro in combination with D and T. Here, we report on the safety and efficacy of this triplet combination in BRAF-mutant melanoma in phase 1 testing. Methods: Key eligibility criteria included BRAFV600E/K-mutant stage III/IV advanced melanoma, ≥ 1 measurable lesion per RECIST v1.1, ECOG PS 0-1, and no prior treatment with BRAF/MEK inhibitors. A 3 + 3 design was used for dose escalation, with dose confirmation in an expansion cohort guided by the toxicity probability interval method. Pts received pembro 2 mg/kg Q3W + D 150 mg twice daily (BID) + T 2 mg daily (QD). AEs (NCI CTCAE v4.0) were collected throughout the study + 30 days; DLT observation window was the first 6 wk after dosing. Primary efficacy end point was ORR (RECIST v1.1, investigator). Results: As of the Jan 2016 data cutoff, 15 pts were enrolled across the dose determination and dose confirmation arms. The predefined criteria for progression to phase 2 were met, with DLTs reported in 3 pts: pt 1 had gr 4 neutropenia (treatment interrupted); pt 2 had gr 4 ALT increased (discontinued); pt 3 had gr 3 ALT, AST, and gamma-glutamyltransferase increased (discontinued). All events resolved. Overall, 10 (67%) pts experienced gr 3-4 treatment-related AEs, with 5 (33%) discontinuations; there were no treatment-related deaths. ORR (unconfirmed) in 15 pts was 60% (n = 9 PR, n = 2 SD, n = 3 PD). Based on these results, the recommended phase 2 regimen is pembro 2 mg/kg Q3W + D 150 mg BID + T 2 mg QD. Conclusions: The approved doses of pembro in combination with D + T administered concurrently provided a manageable toxicity profile in pts with BRAF-mutant melanoma. A phase 2 study will further evaluate safety and efficacy of this triplet combination as first-line therapy for BRAF-mutant melanoma. Clinical trial information: NCT02130466.
Efficacy and safety of additional olanzapine to ondansetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting: A randomized, double-blind, placebo-controlled, crossover study.
Authors: Veerisa Vimolchalao, Siwat Sakdejayont, Ploytuangporn Wongchanapai, Shama Sukprakun, Suleepon Uttamapinan, Nattaya Sintawichai, Nattaya Poovorawan, Sutima Luangdilok, Napa Parinyanitikul, Chanida Vinayanuwattikun, Virote Sriuranpong, Suebpong Tanasanvimon
Journal: Journal of Clinical Oncology (2018)

10019 Background: Currently, the antiemetic regimen consisting of dexamethasone, palonosetron plus a NK-1 antagonist or olanzapine is recommended in prevention of chemotherapy induced nausea and vomiting (CINV) for highly emetogenic chemotherapy (HEC). However, palonosetron and NK-1 antagonists are costly and not accessible for all Thai patients. We sought to evaluate efficacy and safety of the additional olanzapine to ondansetron and dexamethasone for CINV prevention in patients receiving HEC. Methods: We randomly assigned chemotherapy-naïve patients receiving either anthracycline-cyclophosphamide or high dose cisplatin (≥50 mg/m2) regimen, to receive olanzapine or placebo in addition to ondansetron and dexamethasone. All subjects were crossed over to another arm on second-cycle chemotherapy. The primary endpoint was complete response (CR) rate defined as no vomiting and no use of rescue drugs. Results: At first cycle, CR was 69% among the 32 patients receiving olanzapine and 25% among the 32 patients receiving placebo, p < 0.001. CR was significantly better with olanzapine than with placebo in acute phase (0-24 h) (75% vs. 31%, p < 0.001) and delayed phase (24-120 h) (69% vs. 43%, p = 0.038). In analysis after two crossover antiemetic regimens, CR was improved in olanzapine group compared to placebo group in acute phase (72% vs. 33%, p < 0.001), delayed phase (67% vs. 38%, p < 0.001) and overall period (67% vs. 25, p < 0.001). In crossover analysis using visual analog score (VAS), the patients with olanzapine had lower mean VAS in nausea (1.28 vs. 3.05, p < 0.001) and fatigue (3.5 vs. 4.58, p < 0.001) but higher mean VAS in appetite (2.5 vs. 1.55, p = 0.003) and sleepiness (3.26 vs. 2.2, p < 0.001). There were no grade 3 and 4 antiemetic-drug-related toxicities. Mean QT interval change did not different between two groups (-4.30 ms vs. -1.86 ms, p = 0.69). The olanzapine combination was preferable to placebo in 52 of 60 patients (p < 0.001). Conclusions: Without the NK-1 antagonists, the additional olanzapine to ondansetron and dexamethasone significantly improved CINV prevention and was safe in patients receiving HEC.