Background

REGOMA trial showed that regorafenib (REG) significantly improved OS and PFS in patients (pts) with relapsed GBM with respect to lomustine (LOM). REG showed a different toxicity profile compared to LOM. Here, we report final results of the HRQoL assessment, a secondary end point.

Methods

HRQoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and brain module (QLQ-BN20) administered before any MRI assessments, every 8 weeks (+/- 2 weeks) until disease progression. To evaluate treatment impact on HRQoL, questionnaires at progression were excluded. Mixed-effect linear models were fitted for each of the HRQOL domain to examine the change over progression-free time within and between arms. The models included the time of questionnaire assessment, the treatment group and their interaction, as fixed effects, and a compound symmetry covariance structure for the random effects. Differences of at least 10 points were classified as a clinically meaningful change. To correct for multiple comparisons and to avoid type I error, the level of significance was set at P = 0.01 (2-sided).

Results

Of 119 randomized pts, 117 participated in the HRQoL evaluation, and 114 had a baseline assessment (n = 56 REG; n = 58 LOM).

No statistically significant differences were observed in any generic or cancer specific domain during treatment in the REG and LOM arms, or between the two arms, except for the appetite loss scale which was significantly worse in PTS treated with REG (Global mean 14.7 (SD = 28.6) vs 7.6 (SD = 16.0); p = 0.0081). The rate of pts with a clinically meaningful worsening for appetite loss was not statistically different between the two arms (9 out of 24 and 0 out of 13 in the REG and LOM arm, respectively; p = 0.02).

Conclusions

In the REGOMA trial, HRQoL did not change during regorafenib treatment. Pts treated with regorafenib and lomustine reported no significant difference in HRQoL.

Legal entity responsible for the study

Giuseppe Lombardi.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

The cancer treatments bring with it body image challenges, causing low self-esteem and contributing to worsen the quality of life. Chemotherapy (CT)-induced hair loss (HL) is one of the most emotionally distressing side effects of several breast cancer (BC) treatments. The DigniCap system (DCS), using the scalp cooling system, has been shown to reduce CT-induced alopecia (A) in a multicenter prospective trial. The purpose of this prospective observational study was to describe our experience.

Methods

Two DCS device are available at the Brindisi Oncology Dpt. From February 2016 and January 2019, 158 consecutive early stage BC pts who received anthracycline and/or taxane-based treatment were enrolled, post local Ethics Committees approval. A nurse and a psychologist were dedicated for these pts. Success of scalp cooling was defined according to the Dean’s scale: G0=no HL; G1 < 25% HL; G2=25–50% HL; G3=50–75% HL; G4 >75% HL.

Results

A total of 158 women were included in the following treatment cohorts: n = 70 (44.30%) received 4 courses of EC (epirubicin at 90 mg/m2 and cyclophosphamide (c) at 600 mg/m2 intravenously (IV) on day 1, with 21 days between cycles) followed by 12 courses of paclitaxel (P) 80 mg/m2 IV once a week (w); n = 56 (35.4%) received only 4 courses of EC, n = 28 pts (17.7%) P (80 mg/m2 IV once a w) and concurrent trastuzumab (2 mg/Kg IV; loading dose 4 mg/kg) for 12 consecutive doses and n = 4 (2.6%) pts received 4 courses of TC (docetaxel at 75 at 90 mg/m2 and c at 600 mg/m2 IV on day 1, every three w. Median age was 49 years (range 31-74). Overall success was observed in 115 pts (72.8%). Full preservation of the hair (G0) was observed in 37 pts (23.4%), G1 in 47 pts (29.7%) and G2 in 31 pts (19.6%). Most frequent scalp cooling-related symptoms were coldness (n = 129, 81.6%), neck pain (n = 83, 52.2%) and headache (n = 113, 71.5%). Overall, 14.6% (n = 23) of pts discontinued DCS because of unsatisfactory hair preservation (n = 11, 7.0%) and cold discomfort (n = 12; 8.4%). Furthermore we observed a hair growth when DCS was continued for pts with A G3 – G4.

Conclusions

Our results confirmed and reinforced previous evidences, showing that DCS is a good chance to prevent A during CT with anthracycline and/or taxane-based regimen and supported the wider use to all women with early stage BC.

Legal entity responsible for the study

Saverio Cinieri.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Genotyping on cfDNA offers potential advantages in clinical practice for pt selection and serial monitoring of treatment (Tx) efficacy. Clinical relevance of sequential RASmut in cfDNA at different time points during 1L of pt with RASwt solid biopsies (SB) was evaluated.

Methods

Prospective, multi-center study in mCRC pt with RASwt according to SB and treated following standard practice. Liquid biopsies (LB) were collected before starting 1L, at 20 (± 2) weeks (w) and at disease progression (PD). Beaming PCR was used for cfDNA analysis; 3 mutant allele fraction (MAF) cutoffs were considered: 1%, 0.1% & 0.02%.

Results

Median progression-free survival (PFS) was 11.7 months (m) (9.9-13.0) (n = 102). There were no differences in the overall response rate (ORR) according to baseline LB at any cut off, being at MAF 0.02%: 78.7% (68.2- 87.1) in RASwt pt (n = 80) vs 61.5% (31.6 - 86.1) in RASmut pt (n = 13) (OR: 2.32; p = 0.180). MAF was not correlated with total cfDNA levels (p = 0.957). The % of mut cfDNA pt varied along time, with the smallest % at 20 w (Table). There were no emergent mutations at 20 w. Ten pt wt according to baseline LB presented mutations at PD. ORR was 76.9% (63.2 - 87.5) in pt always wt (n = 52) vs 76.2% (52.8 - 91.8) in pt with mut cfDNA at any time point (n = 21) (p = 1.0). There were also no differences in PFS between these 2 groups of pt: 13.0 m (10.9 - 15.4) vs 11.4 m (7.1 – 13.7) at MAF 0.02% (p = 0.095).Table:

531PD

Conclusions

RAS mutational status assessed in cfDNA before starting 1L or sequentially during P+CT Tx in pt with RASwt SB was not a significant predictor of PFS and ORR in none of the cutoffs considered, although in RASmut pt clinical results tended to increase as MAF decreased. The highest proportion of mutated pt was observed at PD, which may be linked to the emergence of resistance. Mutated cfDNA by itself did not predict a lack of clinical benefit to CT and P in our study.

Editorial acknowledgement

Marta Muñoz-Tudurí (TFS, S.L.).

Legal entity responsible for the study

Amgen S.A.

Funding

Amgen S.A.

Disclosure

M. Valladares-Ayerbes: Honoraria (self): Amgen, Merck, Roche, Servier, Bayer, Bristol-Myers; Advisory / Consultancy: Merck, Sanofi, Amgen; Speaker Bureau / Expert testimony: Roche, Servier, Bayer; Research grant / Funding (self): Roche; Travel / Accommodation / Expenses: Merck, Servier, Amgen, Roche. J.M. Viéitez: Travel / Accommodation / Expenses, attendance at conferences: Amgen, Roche, Servier; Research grant / Funding (self): Roche, Amgen. J.J. Cruz-Hernández: Honoraria (self): Amgen, AstraZeneca, Bristol-Myers Squibb, Novartis, Pfizer, Roche Farma; Advisory / Consultancy, Advisory Board: Bristol-Myers Squibb, Merck, MSD, Roche Farma, Pfizer, Janssen Cilag; Advisory / Consultancy, Consulting: Roche Farma. M. Llanos: Advisory / Consultancy, collaboration in lectures: Servier, Roche, Ipsen, Merck, Bristol, Sanofi, Eisai; Advisory / Consultancy: Amgen. A. Lloansí Vila: Shareholder / Stockholder / Stock options, employee and stakeholder of Amgen S.A: Amgen. All other authors have declared no conflicts of interest.

Background

We have recently shown that breast cancer tissue cultures with higher levels of progesterone receptor isoform A (PRA) than isoform B (PRB) were inhibited by antiprogestins. This highlights the relevance of determining the PRA/PRB ratio to identify patients that may benefit from this therapy. The aim of this study was to evaluate the concordance between the PR isoform ratio determined by western blots (WB) in core biopsies and in surgical samples from the same breast cancer patients (n=48) from the Hospital “Magdalena V Martínez” from General Pacheco, Buenos Aires. The protocol has been approved by Institutional Review Boards.

Methods

We determined the PRA/PRB ratio by WB using nuclear extracts from frozen tissues (biopsy and surgery) and the percentage of cells expressing PR measured by immunohistochemistry (IHC) was obtained from the clinical records (surgical samples). The analysis of the concordance between the core biopsy and surgical categorization was performed using the Cohen's Kappa coefficient. To categorize samples according to the PRA/PRB ratio, we considered samples enriched in PRA (PRA-H) those with PRA/PRB ≥ 1.2, those enriched in PRB, (PRB-H) with PRA/PRB ≤ 0.83, and equimolar (EQUI) samples, those with ratios in between 1.2 and 0.83.

Results

A 93% of coincidence was observed between WB and IHC data. The discordant samples had low PR levels determined by IHC (<20%) and proved negative in WB. When these 3 groups of PR+ samples, together with PR negative samples, were analyzed comparing the core biopsy and the surgical categorization, a 77% of concordance and a Kappa coefficient of 0.637 (N=48, p< 0.01) was obtained. However, when PR+ cases in which an agreement with the IHC and the WB data was observed, this value rose to 0.724 (N=18, p<0.01).

Conclusions

This study indicates that the PR isoform categorization from core biopsy specimens reflects the PRA/PRB ratio in the tumor in cases in which PR status observed by IHC and WB from biopsy cores are coincident suggesting the possible use of this tool to potentially predict antiprogestin response in case of neoadjuvant treatment.

Background

The combination of sunitinib (SU) and nivolumab (NI) showed to be safe in the previous phase I of IMMUNOSARC study. We present the results of the phase II of the combination of SU-NI in the advanced STS (pts) cohort.

Methods

Pretreated progressing pts, ECOG 0-1, with UPS, synovial (SS), clear cell (CCS), angio(AS)/epithelioid hemangioendothelioma (EH), solitary fibrous tumor (SFT), epithelioid sarcoma (ES), extraskeletal myxoid chondrosarcoma (ECM) or alveolar soft part sarcoma (ASPS) were eligible. SU 37.5 mg/d as induction was given days 1-14 and then reduced to 25mg/d continuously. NI was administered at 3 mg/Kg every 2 weeks from week 3. SU-NI was maintained up to progression or intolerance. Primary end-point was progression-free survival rate (PFSR) at 6 months (m) by RECIST. Secondary end-points: overall survival (OS), objective response rate (ORR) by RECIST and CHOI and toxicity.

Results

From Nov 2017 to Dec 2018, 50 eligible pts were included in 8 centres: (M/F 30/20), median age 45y (19-77). Diagnosis was: SS in 9 (18%), CCS in 7 (14%), SFT in 7 (14%), UPS in 6 (12%), ES in 6 (12%), AS in 5 (10%), ECM in 4 (8%), ASPS in 3 (6%) and other in 3 (6%). With a median FU of 6.1 m (0-13), 23 pts (46%) progressed based on RECIST with a median PFS of 5.9 m (95% IC 2.7-9.1) and 9 pts (18%) died, with median OS not reached yet. PFSR at 3 and 6 m based on local evaluation were 69% and 50% respectively and OS at 3 and 6 m were 86% and 77%. Based on central radiological review (RECIST, 43 evaluable pts), there were 1 CR (2.3%), 3 PR (7%), 26 SD (60%, 12 pts showing shrinkage) and 13 PD (30%). By CHOI (31 evaluable), there were 19 PR (61.3%), 8 SD (25.8%) and 4 PD (13%). Most relevant G3/4 toxicities were: AST increase 6 (11.8%), ALT increase 5 (9.8%), neutropenia 5 (9.8%), fatigue 3 (5,9%), thrombocytopenia 2 (3.9%), diarrhea 2 (3.9%), renal function impairment 2 (3.9%), without toxic deaths.

Conclusions

The trial met its primary endpoint. SU-NI is an active combination for the treatment of advanced selected STS patients, with 50% of patients free of progression at 6m. Further exploration of immunomodulatory strategies is warranted in selected sarcoma subtypes.

Clinical trial identification

NCT03277924.

Legal entity responsible for the study

Grupo Español de Investigación en Sarcomas (GEIS).

Funding

Pfizer and BMS.

Disclosure

J. Martin Broto: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self): Bayer; Honoraria (self): Amgen; Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Eisai; Research grant / Funding (self): GlaxoSmithKline . N. Hindi: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Novartis. G.E. Grignani: Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: Novartis. A. Redondo: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: Clovis; Research grant / Funding (institution): Eisai. C. Valverde: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Research grant / Funding (institution): Bluprint; Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): Decyphera; Research grant / Funding (institution): Incyte. A. Lopez Pousa: Travel / Accommodation / Expenses: PharmaMar. S. Stacchiotti: Research grant / Funding (institution): Pfizer . E. Palmerini: Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): Bristol-Myers Squibb (BMS); Research grant / Funding (institution): Pfizer; Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Takeda. D.S. Moura: Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai; Research grant / Funding (institution): Novartis. L. D’Ambrosio: Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: PSI. J.A. Lopez Martin: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Celgene; Advisory / Consultancy: Novartis; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties: PharmaMar; Advisory / Consultancy: Chobani; Advisory / Consultancy: Pfizer. All other authors have declared no conflicts of interest.

Background

Abemaciclib, a selective CDK4 & 6 inhibitor, demonstrated single-agent activity in NSCLC and melanoma (Patnaik et al., 2016). Clinical data demonstrate abemaciclib penetrates the blood brain barrier resulting in comparable concentrations in tissues and plasma (Sahebjam et al., 2016).

Methods

Study JPBO is a Simon 2-stage trial evaluating abemaciclib in 6 pt cohorts with BM secondary to HR+ breast cancer, NSCLC, or melanoma. Here, we report NSCLC and melanoma cohorts. Pts with ≥1 new or not previously irradiated BM ≥ 10mm or a progressive BM previously irradiated were eligible. Abemaciclib was orally administered BID on a continuous dosing schedule. Primary endpoint was objective intracranial response rate (OIRR; [confirmed CR+PR]) based on Response Assessment in Neuro-Oncology BM response assessment criteria (RANO-BM). Secondary endpoints included intracranial clinical benefit rate, PFS, OS, and safety.

Results

28 (NSCLC) and 23 (MEL) pts were enrolled and 23 (NSCLC) and 22 (MEL) were evaluable. Pts had a median of 2 prior systemic therapies in the metastatic setting. 35% (NSCLC) and 46% (MEL) of pts had prior whole brain radiotherapy. 35% (NSCLC) and 27% (MEL) pts had stereotactic radiotherapy. Median time from radiation to study enrollment was 4.8 (NSCLC) to 5.6 (MEL) months. No confirmed intracranial response was observed (OIRR 0% for both cohorts). 21.7% (NSCLC) and 13.6% (MEL) of pts showed a decrease in the sum of their intracranial target lesions. ICBR (CR+PR+SD persisting for > 6 months) was 26.1% (NSCLC) and 9.1% (MEL). Median PFS was 1.5 months (95% CI, 1.4-2.8) for NSCLC and 1.2 months (95% CI, 1.0-1.6) for MEL. Median OS was 7.1 months (95% CI, 3.7-9.4) for NSCLC and 2.9 months (95% CI, 1.2-4.3) for MEL. Based on efficacy results, enrollment closed at end of stage 1. Safety and tolerability were similar as previously reported for abemaciclib.

Conclusions

There was limited intracranial clinical activity for abemaciclib monotherapy in NSCLC and MEL pts in this study; OIRR and short median PFS suggest that no further studies for abemaciclib monotherapy are warranted in this pt population.

Clinical trial identification

NCT02308020.

Editorial acknowledgement

Medical writing assistance was provided by Kristi Gruver, employee of Eli Lilly and Company.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

E. Le Rhun: Advisory / Consultancy, Research grant / Funding (institution), Oscar Lambert Center, Lille, FR: Mundipharma; Research grant / Funding (institution), University Hospital, Lille, FR: Amgen; Advisory / Consultancy, personal fees: Novartis; Advisory / Consultancy, personal fees: Daiichi Sankyo; Advisory / Consultancy, personal fees: Abbvie. G. Jerusalem: Advisory / Consultancy, Non-remunerated activity/ies, per patient investigator fee: Eli Lilly and Company; Research grant / Funding (self), Non-remunerated activity/ies, personal fees: Novartis; Research grant / Funding (self), Non-remunerated activity/ies, personal fees: Roche; Advisory / Consultancy, Non-remunerated activity/ies, personal fees: Pfizer; Advisory / Consultancy, personal fees: Celgene; Advisory / Consultancy, Non-remunerated activity/ies, personal fees: Amgen; Advisory / Consultancy, Non-remunerated activity/ies, personal fees: BMS; Advisory / Consultancy, personal fees: Puma Technology; Advisory / Consultancy, Non-remunerated activity/ies, personal fees: AstraZeneca; Advisory / Consultancy, personal fees: Daiichi Sankyo; Advisory / Consultancy, personal fees: Abbvie. D. Subramaniam: Advisory / Consultancy, personal fees: AstraZeneca; Advisory / Consultancy, personal fees: Takeda Oncology; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Genentech. Y. Chen: Shareholder / Stockholder / Stock options, Full / Part-time employment, employee and stock options: Eli Lilly and Company. P.F. Conte: Research grant / Funding (self): Novartis; Travel / Accommodation / Expenses, travel grant: Eli Lilly and Company; Research grant / Funding (self): Roche; Research grant / Funding (self): AstraZeneca; Travel / Accommodation / Expenses, travel grant: Celgene; Travel / Accommodation / Expenses, travel grant: Tesaro. All other authors have declared no conflicts of interest.

Background

NETTER-1 demonstrated that Radioligand Therapy (RLT) with LUTATHERA^® significantly prolongs PFS in progressive midgut neuroendocrine tumor patients compared to 60 mg octreotide (Oct). In oncology, treatment efficacy has often been associated with early reduction of tumor size. As RLT differs from traditional treatments, we sought to verify whether objective tumor shrinkage predicts duration of PFS by assessing the relations between changes in lesion size and treatment efficacy, evaluated by PFS among NETTER-1 patients.

Methods

Post-hoc analyses were performed on the NETTER-1 population on local tumor imaging assessments on the full analyses set (n = 231) with data cut-off date on June 30^th, 2016. The best response (change from baseline in sum of target lesion diameters) during 3 intervals after treatment onset was used as a covariate in a Cox regression, thus differentiating whether the time corresponds to an event or a censoring. One interval corresponded to 150 days, i.e. a month prior to 4^th injection; 180 days matched the 4^th injection and the last interval was set to no limit.

Results

For patients treated with Oct, Cox regression showed a HR of 0.914 [95% CI: 0.860 – 0.971], p = 0.0034. This suggests that the risk of disease progression decreases by 9% for each incremental percentage of shrinkage. Among the patients treated with Lu, Cox regression showed a HR of 1.006 [0.982 – 1.03] p = 0.6236, suggesting that LUTATHERA^® prolonged PFS even when tumor objective response was undetected during treatment cycles. As a sensitivity, a 180-day-limit and no-limit (i.e. using the best response up to time of censoring/event) were also applied. With the 180-day-limit, HRs were 0.952 [0.904 - 1.003], p = 0.0652 and 1.013 [0.991-1.037], p = 0.2523 for Oct and Lu, respectively; similarly the no-limit, HRs were 0.952 [0.922, 0.982] p = 0.0023 and 1 [0.984, 1.017] p = 0.9713.

Conclusions

Durable response of LUTATHERA^® treatment goes beyond objective tumor shrinkage. This study conveys crucial information on the patient’s management with respect to LUTATHERA^®: treatment benefit of 4 cycles should not be assessed only by objective tumor shrinkage.

Clinical trial identification

NETTER-1: NCT01578239.

Legal entity responsible for the study

Advanced Accelerator Applications.

Funding

Advanced Accelerator Applications.

Disclosure

M.E. Pavel: Advisory / Consultancy: Novartis. P. Broberg: Full / Part-time employment: Advanced Accelerator Applications. M. Caplin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Advanced Accelerator Applications. P. Ruszniewski: Speaker Bureau / Expert testimony: Advanced Accelerator Applications. P. Santoro: Full / Part-time employment: Advanced Accelerator Applications. L. Ravasi: Full / Part-time employment: Advanced Accelerator Applications. All other authors have declared no conflicts of interest.

Background

Current diagnostic approaches for pancreatic cancer (PC) mostly rely on cytologic examination of endoscopic ultrasound fine-needle aspiration (EUS-FNA) samples. However, in a subset of cases, PC diagnosis remains inconclusive due to low tumour cellularity. Molecular analysis of EUS-FNAs might be used as an auxiliary tool to strengthen diagnosis in samples with suboptimal cytology. This study aimed to evaluate the diagnostic utility of a single nucleotide variants (SNV) assay using molecular barcode technology performed on EUS-FNAs.

Methods

28 EUS-FNA samples of pancreatic masses (19 PC, 9 non-malignant lesions) were analyzed. FNAs were collected in RNAlater and stored at -80 C. Mutational status was evaluated using the Nanostring Vantage 3D™ DNA SNV Solid Tumor Panel, utilizing digital enumeration of unique barcoded probes to detect 104 SNV from 24 genes of clinical significance. 5ng of tumor-derived DNA was subjected to multiplexed preamplification and hybridization of variant-specific probes to unique fluorescent barcodes. A multiplex KRAS assay (G12/13) droplet digital PCR (ddPCR) was used to confirm SNVs.

Results

The SNV assay detected at least one variant in 18/19 (95%) PC samples. One PC case harbored 3 SNVs. Among the PC samples, KRAS variants (G12D, G12V, G12R, Q61H, Q61L) were detected in 17 (90%) cases, EGFR in 1 (5%), and PIK3CA in 1 (5%). All KRAS mutations were also detected by ddPCR. Diagnostic accuracy of cytology alone for PC was 68% (19/28). 32% of the FNAs were inconclusive; at least one SNV was detected in 5/6 inconclusive FNAs with a final diagnosis of PC. No SNV was identified in the remaining 3 inconclusive cases diagnosed as chronic pancreatitis. Combining cytology and SNV analysis for inconclusive cases increased the diagnostic accuracy to 96% (27/28).

Conclusions

Nanostring SNV assay combined with cytology can enhance the diagnostic power of EUS-FNA, especially in inconclusive cases, preventing repeat biopsies, unnecessary resections for benign disease or delay in PC patients care. Given the low DNA input, digital data output and rapid turn-around time, this novel technology may be instrumental for the preoperative molecular diagnosis of PC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Oral pain, odynophagia and dysphagia, weight loss, dehydration, systemic infection, feeding support and hospitalization should be mentioned as the main determinated effect of oral mucositis (OM); this toxicity is often linked to chemo- or chemoradiotherapy. Oral Mucositis can reduce patients’compliance to cancer treatment and decreased their quality of life; it could be also reduce survival caused by discontinuation or dose reduction of anti-neoplasm therapy. The purpose of this study is to evaluate the impact of the three different products on OM outcomes of patients who received radio and chemotherapy in solid cancer.

Methods

From March to June 2018, 60 patients (pts) were randomized by Medical Oncology Unit of Rho - Milan. The pts were divided in 3 arms, belanced for tumor site and treatment, to receive the following medical devices: Gelx (oral spray), Episil (oral solution) and Gelclair (oral gel). Primary aim of the study was evaluation of OM onset, severity, reduction or remission and pain relief with the three devices in study. We analysed data with forms compiled by pts in 2 different steps: T0 (baseline) and follow-up (after 16 w); the clinicians evaluated OM grade in 2 steps: after 4 w and after 8 w. The pts’safety profile form included 10 items concerning difficulty of speaking, feeding, drinking and change of taste.

Results

The data analysis showed a significant difference among the 3 Groups. OM grade of Group 2 after 4 weeks is higher if compared with Group 1 and Group 3 After 4 weeks two cases of grade 4 mucositis has been achieved in Group 2, none in Group 1 and Group 3. Group GELX (Zinco gluconate included) demonstrated an overall better efficacy, in every analyzed safety profile items.

Conclusions

Even if prevention and treatment of OM are not yet clearly defined and recognized in the clinical practice, the study shows how the correct use of anti- mucositis product (accompanied by an appropriate hygienic and dietetic regimen) seems to be effective in the prevention of this pathology, which is the most frequent side effects on patients undergoing chemotherapy.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

In the recent years, there has been an increased incorporation of research biopsies in clinical trials and translational research. However, limited information is available on the determinants of sample quality, which could help identifying parameters for successful biopsy ascertainment.

Methods

Data from all consecutive patients who had one or more research biopsies at our institution as part of a phase I-III trials and/or translational research projects approved by Ethics Committee from January 2017 to December 2018 were extracted and analyzed.

Results

A total of 1517 procedures were performed in 979 consenting patients, reaching in total 3811 tissue samples (71% at screening and 29% on-treatment or at progression) with an average of 2.5 samples per procedure. Tumor biopsies were obtained under ultrasound (60%), computed tomography (12%) guidance or non-guided (28%). Samples were formalin-fixed and paraffin embedded (FFPE, 48%), snap frozen (20%) or alternatively stabilized (32%) according to study protocol. Tumor content (TC) was determined in 1514 FFPE samples: 90% of them had tumor cells, 81% showed more than 10% TC and 59% more than 50% TC. No significant difference in TC was found between screening and on-treatment biopsies (p = 0.12). Sample quality was negatively affected by biopsy site (<10% TC rates in non-visceral vs visceral were 26% vs 14%, respectively, p<.0001), method (non-guided vs guided, 37% vs 17%, p<.0001), and operator expertise (<50 vs > 50 biopsies x year, 31% vs 16.5%, p<.0001). In a multivariate logistic model, biopsy site and method were independent determinants of poor sample quality (<10% TC). Within the same biopsy procedure, inter-sample variability was low with 77% of samples showing between 0% to 30% difference in TC. Among 134 intra-trial sequential biopsies with available TC assessment, only 25% pairs were not suitable for performing downstream comparative analyses (<10% TC).

Conclusions

Our experience provides important information to improve research biopsy effectiveness in a biomarker program linked to clinical trials.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P.G. Nuciforo: Honoraria (self): Bayer; Honoraria (self): Novartis; Honoraria (self): MSD. C. Saura: Advisory / Consultancy: AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Roche, Genomic health, Novartis, Pfizer, Pierre Fabre, Puma, Synthon and Sanofi; Travel / Accommodation / Expenses: AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Roche, Genomic health, Novartis, Pfizer, Pierre Fabre, Puma, Synthon and Sanofi. E. Elez: Honoraria (self): Hoffman La-Roche, Bristol Myers Squibb, Servier, Amgen, Merck Serono, Array, Sanofi; Advisory / Consultancy: Hoffman La-Roche, Bristol Myers Squibb, Servier, Amgen, Merck Serono, Array, Sanofi; Research grant / Funding (self): Hoffman La-Roche, Bristol Myers Squibb, Servier, Amgen, Merck Serono, Array, Sanofi; Honoraria (institution): Array, MSD, Abbvie, Amgen, GSK, AstraZeneca, Bristol Myers Squibb, Novartis, Boehringer, Ingelheim, Hoffman La-Roche.. E. Felip: Speaker Bureau / Expert testimony: AbbVie, AstraZeneca, Blueprint medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardant Health, Janssen, Medscape, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Touchtime.; Advisory / Consultancy: AbbVie, AstraZeneca, Blueprint medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardant Health, Janssen, Medscape, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Touchtime.; Research grant / Funding (institution): Fundación Merck Salud, Grant for Oncology Innovation EMD Serono. A. Oaknin: Advisory / Consultancy: Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro, Inmunogen and Genmab; Travel / Accommodation / Expenses: Roche, AstraZeneca, and PharmaMar. E. Muñoz-Couselo: Advisory / Consultancy: Amgen, Bristol-Myers Squibb, Merck, Sharp & Dohme, Novartis, Pierre Fabre, and Roche; Honoraria (self): Amgen, Bristol-Myers Squibb, Merck, Sharp & Dohme, Novartis, Pierre Fabre, Sanofi and Roche ; Leadership role, Clinical trial participation (principal investigator): Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Sharp & Dohme, Novartis, Pierre Fabre, and Roche. T. Macarulla Mercade: Advisory / Consultancy: Shire Pharmaceuticals, Roche, Tesaro, Batxer, Sanofi, Celgene, QED Therapeutics, Genzyme Europe, Baxalta, Bayer, Incyte, Genzyme ; Travel / Accommodation / Expenses: from Merck, H3 Biomedicine, Bayer, Sanofi. M. Alsina Maqueda: Advisory / Consultancy: Servier, Lilly, BMS and MS. Honoraria for speaking issues from Servier, BMS, MSD, Lilly, Roche and Amge; Travel / Accommodation / Expenses: Servier, Roche, Amgen and Lilly. J. Carles: Advisory / Consultancy: Bayer / Johnson & Johnson / Bristol-Myers Squibb / Astellas Pharma / Pfizer / Sanofi / MSD Oncology / Roche/ AstraZéneca; Speaker Bureau / Expert testimony: Bayer / Johnson & Johnson / Asofarma / Astellas Pharma; Research grant / Funding (institution): AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, INC, Astellas Pharma., AstraZeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim España, S.A., Bristol-Myers Squibb Inter. R. Dienstmann: Advisory / Consultancy: Roche; Research grant / Funding (self): Merck. J. Tabernero: Advisory / Consultancy: Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Part. E. Garralda: Advisory / Consultancy: F.Hoffmann-La Roche, Ellipses Pharma, Neomed Therapeutics1 Inc, Boehringer Ingelheim, Janssen Global Services, ; Speaker Bureau / Expert testimony: Bristol-Mayers Squibb ; Travel / Accommodation / Expenses: Merck Sharp & Dohme, Glycotope, Menarini; Research grant / Funding (self), Scitron Project - VHIO Technology : Novartis; Research grant / Funding (institution), Clinical Trial Principal Investigator: Principia Biopharma Inc, Lilly, S.A, Novartis, Genentech, Loxo Oncologi Inc, F.Hoffmann-La Roche Ltd, Symphogen A/S, Merck, Sharp & Dohme de España, S.A, Incyte Biosciences International, Pharma Mar, S.A.U, Kura Oncology Inc, Macrogenics Inc, Glycotope G; Leadership role: ESMO Women for Oncology - W4O. All other authors have declared no conflicts of interest.

Background

Pem, an immune checkpoint inhibitor, has been demonstrated to be active in various neoplasms with MMRd. No data exist about its efficacy in MMRd glioma patients.

Methods

MMRd HGG patients relapsed after receiving RT and CT were treated with Pem. MMR status was analyzed by immunohistochemistry, including the MLH1, MSH2, MSH6, and PMS2 markers. MMR deficiency was defined as presence of a weak (wMMRd) or absent (aMMRd) signal on immunohistochemistry for at least one MMR protein. Other inclusion criteria were: ECOG PS 0-2, histologically confirmed gliomas, dexamethasone ≤4 mg. Pem was administered at 200 mg every 3 weeks until disease progression or unacceptable toxicity. Tumor response was evaluated by brain MRI every 10 weeks according to the RANO criteria. OS and PFS were evaluated by Kaplan-Meier curves. CTCAE v4.0 was used for toxicity assessment.

Results

Among 167 glioma patients, we found 22 MMRd gliomas. 12 PTS were treated with Pem: 8 wMMRd and 4 aMMRd. According to Bethesda criteria, all PTS had microsatellite stability. Tumor histologies included 5 anaplastic astrocytoma, 1 anaplastic oligodendroglioma, 6 glioblastoma (GBM). MSH2 deficiency was found in 6 cases, MSH6 deficiency in 9 cases, PMS2 and MLH1 deficiency in 2 cases. Median number of prior lines of chemotherapy was 1 (range 1-5). Stable disease (SD) was reported in 4 PTS (33%); 8 PTS showed progressive disease (PD). PTS with anaplastic gliomas showed a statistically significant association with SD (p = 0.03, OR = 3); all GBM PTS reported PD; status of MMRd (weak/absent), IDH (mutated/wild-type), MSH2 and MLH6 (deficient/proficient) were not associated with SD. Median follow up was 14.7 ms. OS was 5.6 ms (95% CI 0.1-13.8), PFS 2.4 ms (95% CI 1.8-2.9). OS was 2.8 ms and 5.6 ms (p = 0.9), PFS was 1.8 ms and 3.1 ms (p = 0.5) in PTS with wMMRd and aMMRd. PTS reporting SD and PD had PFS of 7.4 ms (95% CI 4.6-10.2) and 1.8 ms (95% CI 0.2-3.4), p = 0.002; OS was “not reached” and 2.8 ms in PTS having SD vs PD (p = 0.04). Grade ≥3 adverse events were reported in 8% of PTS.

Conclusions

A subgroup of recurrent MMRd HGG patients might benefit from Pem, especially those with anaplastic gliomas. There was a trend for a longer PFS and OS in PTS with aMMRd. Analyses for identifying additional molecular predictive factors is ongoing.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

D and E demonstrated to be efficacious in the treatment of mCRPC pts. Due to different antitumor mechanism of action of these agents, it could be postulated that their combination can improve disease control. CHEIRON study tried to demonstrate the candidate efficacy of chemo-hormonal combination D+E versus D in mCRPC first-line.

Methods

Eligibility criteria included mCRPC diagnosis, ECOG PS ≤ 2, adequate renal, hepatic and hematological functions, no prior treatment for mCRPC. Pts were randomized to receive D 75 mg/m² IV d1 q3w plus prednisone 5 mg PO BID for 8 courses alone or plus E 160 mg PO daily for 24 weeks. Stratification criteria were presence of pain and visceral metastases. The primary endpoint of the study was the rate of pts without disease progression (according to PCWG2) at 6 mos after randomization.

Results

Between 09/2014 and 10/2017, 246 pts (median age 70 years, range 44-88, pain reported by 54 pts, visceral metastases present in 50 pts) were randomized to DE (120) or D (126). The rate of pts without disease progression at 6 mos was significantly higher in DE arm compared to D arm (89.1% vs 72.8%; p = 0.002). Similarly, a higher proportion of DE pts achieved a PSA reduction ≥ 50% compared to the baseline values compared to the D pts (92% vs 69%; p < 0.0001). No differences were observed in terms of objective response rate. Major haematological toxicities consisted of grade 3-4 neutropenia (19 pts DE – 15 pts D); febrile neutropenia was observed in 10 DE pts and in 7 D pts. At a median follow-up of 24 mos, the median progression free survival was 10.1 mos and 9.1 mos in DE and D arm, respectively (p = 0.01). In DE arm the median overall survival was 33.7 mos compared to 29.6 mos of the standard arm (p NS).

Conclusions

The present study was the first phase II randomized trial, which tested the addition of a new generation hormone agent to D compared to D alone. From this data, DE improved the 6-mo disease control with a prolongation of PFS compared to the standard chemotherapy.

Clinical trial identification

NCT02453009.

Legal entity responsible for the study

The authors.

Funding

Astellas.

Disclosure

O. Caffo: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: AstraZeneca. D. Gasparro: Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony: Astellas; Speaker Bureau / Expert testimony: Pfizer. R. Iacovelli: Advisory / Consultancy: Astellas; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Novartis. U.F.F. De Giorgi: Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Janssen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi. G. Pappagallo: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy: Genzyme; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Honoraria (self): Roche. M. Aglietta: Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: Novartis; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self): PharmaMar; Travel / Accommodation / Expenses: Tesaro. All other authors have declared no conflicts of interest.