Found 5 Presentations For Request "Benedetta Pellegrino"

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Breast cancer, early stage

145P - High-risk breast cancer patients with RAD51-low tumors are characterized by good prognosis

Presentation Number
145P
Speakers
  • Benedetta Pellegrino (Parma, Italy)

Abstract

Background

Triple-negative breast cancer (TNBC) that do not achieve pathological complete response (pCR) have unfavorable prognosis. The RAD51 score is a functional assay able to identify Homologous Recombination Repair (HRR)-deficient tumors. In this setting, it may add prognostic value and guide post-neoadjuvant treatments.

Methods

We quantified RAD51 and BRCA1 foci by immunofluorescence, content of tumor-infiltrating lymphocytes (TIL) and expression of immune markers on diagnostic biopsies of 26 high-risk breast cancer (BC) patients (pts), namely TNBC or early onset BC (≤ 35 yo) or gBRCA1/2-mutated BC admitted at the University Hospital of Parma from 01/2011 to 03/2020. All pts received neoadjuvant chemotherapy (neoCT) with epirubicin, taxanes and cyclophosphamide. Functional HRR deficiency (HRD) was predefined as a RAD51 score ≤10% (RAD51-low).

Results

RAD51 was successfully scored in 26/29 (90%) samples. 16/26 (62%) tumors were RAD51-low (HRD). 14 pts presented HRR alterations: 4 gBRCA1, 2 gBRCA2 and 2 gPALB2 mutations and 6 BRCA1-low foci, surrogate of lack of BRCA1 function likely due to promoter hypermethylation. Median RAD51 score was 3.4 in HRR-mutated tumors and 19.2 in HRR-WT tumors (p=.01). Disease-Free Survival (DFS) at 4 years was 100% for pts who achieved pCR vs 67.5% for non-pCR tumors (p=.12). The addition of RAD51 status to pCR information improved the model capacity to predict DFS (ANOVA test, p=.05). Pts with HRD tumors by RAD51 showed a trend towards better DFS (HR=0.28, 95% CI 0.05–1.54, p=.14). 4/5 TIL-high tumors in this cohort were RAD51-low, suggesting a crosstalk between HRD and an active antitumor immune response. In support, RAD51-low/TIL-high tumors had higher CD20+ TIL (p=.01), lower CD3+ TIL (p=.02), higher PD-L1 Combined Positive Score (p=.03), and a trend towards higher PD1+ TIL (p=.05); no differences were found in FOXP3+ TIL. Moreover, only 1/4 RAD51-low/TIL-high tumors achieved pCR but none of them relapsed.

Conclusions

The RAD51 test is able to identify HRR-altered tumors, beyond gBRCA1/2 mutations, and to select a cohort of RAD51-low pts with better prognosis in a platinum-free neoCT setting. Biomarker analyses on treated paired tumors and on a larger cohort of pts are ongoing. Results will be available for the congress.

Legal entity responsible for the study

The authors.

Funding

B.P. was supported by ESMO with a Clinical Translational Fellowship aid supported by Roche. This work was supported by the project ERAPERMED2019-215.

Disclosure

B. Pellegrino: Non-Financial Interests, Institutional, Sponsor/Funding: Novartis; Financial Interests, Institutional, Writing Engagements: BMS; Non-Financial Interests, Institutional, Sponsor/Funding: Lilly. V. Serra: Non-Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Sponsor/Funding: Abbie. A. Musolino: Non-Financial Interests, Institutional, Research Grant: EISAI; Non-Financial Interests, Institutional, Research Grant: Ltd.; Financial Interests, Personal, Sponsor/Funding: Roche; Financial Interests, Personal, Sponsor/Funding: MacroGenics; Financial Interests, Personal, Sponsor/Funding: Merck; Financial Interests, Personal, Sponsor/Funding: Lilly; Non-Financial Interests, Institutional, Research Grant: Pfizer. All other authors have declared no conflicts of interest.

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SARS-CoV-2 and cancer

1587P - SARS-CoV-2 infection risk and COVID-19 prevalence in cancer patients during the first wave of COVID-19 pandemic in a Northern Italy’s virus epicenter area

Presentation Number
1587P
Speakers
  • Antonino Musolino (Parma, Italy)

Abstract

Background

Patients (pts) with cancer are purported to be more vulnerable to coronavirus disease 2019 (COVID-19). However, cancer encompasses a spectrum of heterogenous tumor subtypes. The aim of this study was to investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk and COVID-19 prevalence according to tumor subtype in the resident cancer population of the Province of Parma (Emilia Romagna Region, Nothern Italy) during the first wave of COVID-19 pandemic in Italy.

Methods

We analyzed data from the Parma Province Cancer Registry, COVID-19 hospital medical records, and local surveillance system of all laboratory-confirmed cases tested positive for SARS-CoV-2 from the beginning of the outbreak (February, 20) to July 19, 2020. All the Parma resident cancer population was classified as either “active” or “inactive” according to the evidence of any referral to health services, for any reason, during the observation period. Study analyses were adjusted for patient demographics, tumor subtype and period of cancer diagnosis.

Results

40,148 cancer pts (mean age 68; 57.8% females; 45.1% active) were analyzed. The cumulative risk of SARS-CoV-2 infection was 11.2% for cancer pts vs. 7% for non-cancer subjects (P < 0.0001). The overall COVID-19 attack rate was 2.2% (95% CI, 2.0-2.4) and 2.6% (95% CI, 2.4-2.9) for inactive and active cancer pts, respectively. The cumulative incidence of COVID-19 was higher in active vs. inactive cancer subjects (HR 1.18, P = 0.01). In the active cancer group, the cumulative incidence of COVID-19 was higher in lung cancer pts vs. other tumors (HR 4.3). In the same group, HR for breast cancer pts was 0.86. Interestingly, the subgroup analysis of COVID-19 cumulative incidence showed a significant interaction between active patient status and hematological malignancies.

Conclusions

In our study, cancer pts were more susceptible to SARS-CoV-2 infection. The cumulative incidence of COVID-19 was higher in active vs. inactive cancer subjects. However, cancer is a heterogeneous group of diseases and pts with different tumor types had differing susceptibility to COVID-19 phenotypes. COVID-19 fatality rates for subgroups will be reported at the meeting.

Legal entity responsible for the study

University Hospital of Parma.

Funding

Has not received any funding.

Disclosure

A. Musolino: Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Macrogenics; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Seagen. B. Pellegrino: Financial Interests, Personal, Research Grant: Roche. All other authors have declared no conflicts of interest.

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Breast cancer, metastatic

261P - Survival outcomes of triple-negative breast cancer (TNBC) patients in the pre-immunotherapy age: An analysis of Gruppo Italiano Mammella (GIM) 14 BIOMETA study with a focus on biological subtypes

Presentation Number
261P
Speakers
  • Luigi Cerbone (Genova, Italy)

Abstract

Background

TNBC is a subtype of Breast Cancer (BC) associated with an overall survival (OS) of around 19 months (ms). Before immunotherapy, no specific systemic treatment apart from chemotherapy (CT) was available. ER low disease is characterized by low ER and PgR staining (both <10%) and negative Her2. It’s considered as having a survival and a biological behavior comparable to that of TNBC. Deleterious germline BRCA mutations were the only predictive biomarker available in the past years for TNBC.

Methods

Patients (pts) were identified within the GIM-14 study, an ambispective multicenter Italian study including pts with metastatic breast cancer diagnosed from 2000 to 2020. TNBC and ER low pts were eligible to this analysis. Pts demographics, disease characteristics and treatment patterns were obtained for each patients. OS and 1st line Time to Treatment Failure (TTF) were calculated. Statistical analysis was performed with SAS v 9.4.

Results

Overall, 195 pts were eligible (158 TNBC and 37 ER low pts). BRCA mutation was assessed in 35 pts (18%), of whom 16 were pos and 19 neg. Pts’ characteristics are summarized in the table. Median (m) OS was 22.6 ms (95% CI: 18.6-26.8); 84% and 57% of pts were alive at 1 and 2 years respectively. M TTF was 4.4 ms (95% CI: 3.8-5.1). MOS of TNBC pts was 20.2 ms (95% CI: 16.9-24.9) while for ER low pts was 26.8 ms (17.4-73 ms); p 0.07. First line mTTF was 4.3 ms (95% CI: 3.7-4.9) for TNBC and 5.5 ms (95% CI: 3.7-9.3) for ER low pts, p 0.1. mOS in BRCA pos pts was 35 ms (19.6-NR) while for BRCA neg 16.3 was ms (95 CI%: 9-32), p 0.03. TTF was 6.9 ms (95%CI: 2.1-8) for BRCA pos pts and 3.9 ms for BRCA neg pts (95%CI: 1.4-6.6), p 0.44.

Variable N=195
Age (mean) 58
Menopause No Yes NA 47(24%)131(67%)17(9%)
Disease Subtype TNBC ER low 158(61%)37(39%)
BRCA BRCA + BRCA – NA 16(8%)19(10%)160(82%)
De novo metastatic YesNoNA 43(16%)121(62%)21(22%)
Metastatic Sites Non visceralBoneVisceral (liver,lung, brain)NA 53(27%)31(16%)105(54%)6(3%)
N° of metastatic sites 123NA 94(48%)48(25%)48(25%)5(2%)
N°of CT lines 12≥3NA 61(31%)42(22%)87(44%)5(3%)
1st line CT AnthraTaxane (without beva)Taxane + bevaPlatinumCapecitabineOtherMissing 22(11%)26(13%)37(19%)21(11%)16(8%)44(23%)29(15%)
Stage at localized disease IIIIIINA N=12123(19%)55(46%)33(27%)10(8%)
Adjuvant CT YesNoNA N=121110(91%)7(6%)4(3%)

Conclusions

In this analysis OS of TNBC pts was comparable to that previously reported in literature. BRCApos pts showed a better OS when compared to BRCAneg pts. A trend towards a better OS in ER low pts was found. Further prospective investigation in this subgroup of pts is warranted.

Clinical trial identification

NCT02284581.

Legal entity responsible for the study

Consorzio Oncotech.

Funding

Has not received any funding.

Disclosure

M. De Laurentiis: Financial Interests, Personal, Speaker’s Bureau: Novartis, Roche; Financial Interests, Personal, Advisory Role: Amgen; Celgene; Eisai; Genomic Health; Lilly; MSD Oncology; Novartis; Pfizer; Pierre Fabre; Roche; Financial Interests, Institutional, Funding: Eisai; Italfarmaco; Roche; Financial Interests, Personal, Other: Amgen; Celgene; Eisai; Genomic Health; Lilly; MSD Oncology; Novartis; Pfizer; Pierre Fabre; Roche . G. Arpino: Financial Interests, Personal, Other: Roche, Pfizer, AstraZeneca, Novartis, Celgene, Eli Lilly, Amgen, Eisai. A. Fabi: Financial Interests, Personal, Other: Roche, Celgene, AstraZeneca, Eli Lilly, Novartis, Pfizer, Eisai. C. Mulinelli: Non-Financial Interests, Personal, Other, honoraria: Novartis. M. Lambertini: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Eli-Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Theramex; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Sandoz; Financial Interests, Personal, Speaker’s Bureau: Novartis. C. Bighin: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Pfizer. L. Del Mastro: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Eli Lilly, MSD, Pfizer, Ipsen; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Roche, Novartis, Eli Lilly, MSD, Genomic Health, Pierre Fabre, Daiichi Sankyo, Seagen, astraZeneca, EIsai. All other authors have declared no conflicts of interest.

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SARS-CoV-2 and cancer

1633P - Why do cancer clinical trials (CT) discontinue prematurely in the era of COVID-19?

Presentation Number
1633P
Speakers
  • Giovanni Maria Iannantuono (Rome, Italy)

Abstract

Background

The COVID-19 pandemic (C19P) is causing several detrimental effects on cancer care globally. CT are crucial to obtain high quality literature evidence and “poor accrual” is the most common reason for their early discontinuation (ED). At our best knowledge, no data are available on ED of cancer CT after the beginning of C19P.

Methods

ClinicalTrial.gov was queried for terminated (T), withdrawn (W) and suspended (S) CT for the following terms: “cancer”, “neoplasm”, and “tumor”. The search was made for all the CT available from the inception to 26th February 2021, without any restrictions. The following characteristics were extracted: reason for ED, study type (interventional [In] vs observational), sponsored (yes vs not). ED rate was compared between CT discontinued for C19P or not (χ2); p<0.05 was set as statistically significant. A multiple linear regression analysis was also conducted to identify independent factors of ED.

Results

9990 CT were identified, but 765 CT were excluded as not related to cancer. Thus, 9225 CT were included (66% was T, 23% was W and 4% was S). Among CT classified as T, W and S, the frequency of In CT was 92%, 88% and 85% respectively, while the frequency of sponsored CT was 46%, 35% and 26% respectively. The most common reasons for ED were: “poor accrual” (29%), “lack of funding” (6%) and “sponsor decision” (5%). No reason for ED was available for 15% of CT. One hundred (1%) CT were discontinued due to C19P (27% was T, 7% was W and 66% was S). Comparing CT discontinued due to C19P with those discontinued due to other reasons, a lower rate of In-CT (73% vs 91%, p<0.05) and sponsored CT (14% vs 42%, p<0.05) was found in the C19P group. At the multiple linear regression analysis, C19P was strongly positively correlated with ED (coefficient 0.59952, p<0.0001) whereas sponsored CT resulted as negatively correlated with ED (coefficient -0.02746, p<0.0001).

Conclusions

“Poor accrual” continues to be the main reason for ED of cancer CT, but C19P represents a new additional cause of ED. Sponsored trials showed less risk for ED. Further research is needed to maximize the expected benefit of cancer CT, reducing the anticipated risks.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Supportive care

1712P - Safety and efficacy of influenza and pneumococcal vaccines in cancer patients on active therapy: A prospective study

Presentation Number
1712P
Speakers
  • Nicla Maria La Verde (Milan, Italy)

Abstract

Background

Influenza virus and S. pneumoniae infections in cancer patients (pts) are responsible of a higher morbidity and mortality rates. Limited data are available about safety, efficacy, immunogenicity and timing of influenza (I) and pneumococcal (P) vaccine (vax) in pts receiving active treatment. However, I and P vax in cancer pts and their family members (FMs) are reccomended.

Methods

This is a single institution prospective study conducted at L. Sacco Hospital (Milan, Italy) between Sept 20 and Apr 21. The aim was to assess efficacy and safety of vax. Cancer pts, age>18yo, in active antineoplastic treatment and FMs age>18yo were included. Each pt received I+P vax on the same day of therapy. Any local and systemic Adverse Event (AE), episode of Influenza Like Illness (ILI), pneumococcal infection (PI), access to Emergency Department (ED) or Hospital admission (HA) and delay of therapy (DoT) were recorded. The frequency of AEs, ILI episodes and PI among pts and age- and gender- matching FMs were compared.

Results

194 pts (63y median age, 67.5% female) and 140 FMs (59y median age, 49% female) were enrolled. CANCER: 92% solid and 8% hematological malignancy, 69% metastatic stage. TREATMENTS: 54% ≥1 previous line of therapy; 38% chemotherapy, 31% target, 17% chemo+target, 14% hormone therapy. VAX: I-vax received for first time in 47% pts and 72% FMs. 100% pts and 49% FMs received I+P-vax. LOCAL AEs: I-vax: 34% pts and 19.6% FMs (p=0.01). P-vax: 35.7% pts and 20.7% FMs (p=0.11). The most common was pain in site of injection. SISTEMIC AEs: 19.6% pts and 8.5% FMs (p=0.11); the most frequent was fatigue. EFFICACY: ILI were recorded in 8.8% pts (3 had a HA and 1 a DoT) and 3.6% FMs (p=0.04). No PI was recorded. In a logistic regression analysis type of therapy, previous treatment and the use of steroid don’t significantly impact on vax safety and efficacy.

Conclusions

Few ILI events were observed due to vax and probably to all measures adopted to prevent SARS-CoV-2 virus spread. Except for local I-vax AEs, no differences were observed in efficacy and safety between the 2 groups. During the observation time, >70% of cancer pts in active treatment received I and P vax, so the vaccination coverage was achieved, reducing the pressure on territorial healthcare system.

Clinical trial identification

Trial protocol n. 2020/ST/433 release by Local Ethic Committee.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

N.M. La Verde: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Speaker’s Bureau: Gentili; Financial Interests, Institutional, Funding: EISA. D. Dalu: Financial Interests, Personal, Invited Speaker: Gentili; Financial Interests, Personal, Other: MSD. A. Riva: Financial Interests, Personal, Other: MSD,; Financial Interests, Personal, Other: ViiV; Financial Interests, Personal, Other: Gilead; Financial Interests, Personal, Other: Janseen; Financial Interests, Personal, Other: Cilag. S. Antinori: Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Merck. M. Galli: Financial Interests, Personal, Other: ViiV; Financial Interests, Personal, Other: BMS; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: AbbVie; Financial Interests, Personal, Other: Gilead; Financial Interests, Personal, Other: Janssen; Financial Interests, Personal, Other: Roche. All other authors have declared no conflicts of interest.

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