Background

MonarchE demonstrated that adjuvant abemaciclib, oral CDK4 & 6 inhibitor + endocrine therapy (ET) significantly improved invasive disease-free survival in HR+, HER2- high-risk early breast cancer (EBC) compared to ET alone. As prescribing practices for ET vary in younger patients (pts), we present here disease characteristics and ET choice in premenopausal pts (preM) enrolled in monarchE.

Methods

Patients with, invasive, resected, HR+, HER2- node positive, high risk, EBC were randomly assigned 1:1 to adjuvant ET +/- abemaciclib in monarchE. Disease characteristics, prior chemotherapy, and ET patterns were examined by menopausal status at initial diagnosis: preM and postmenopausal pts (postM). ET choices for preM are further described by age.

Results

Of the 5637 pts, 43.5% and 56.5% were preM and postM, respectively, with an even distribution between both arms. Median age for preM and postM was 44 and 59 years (y), respectively; 31.5% of preM were ≤40y. PreM had larger tumor size and higher rates of neoadjuvant chemotherapy administration compared to postM (Table). Aromatase inhibitor (AI) use was higher in postM, while tamoxifen use was higher in preM. Among preM, AI use was highest in preM ≤40y in both arms (49.9% abemaciclib + ET, 49.4% ET) and tamoxifen use was highest in preM >40y to ≤50y in both abemaciclib + ET and ET arms, 60.1% and 65.0%, respectively. Table: 153P

Summary of baseline characteristics and first endocrine therapy for premenopausal and postmenopausal patients

Conclusions

PreM had larger tumors at baseline and were more likely to have received neoadjuvant chemotherapy, suggesting they may have a higher risk of recurrence than PostM.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

The authors would like to thank Garreth Lawrence, who is an employee of Eli Lilly and Company, for their writing and editorial contributions.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

S. Paluch-Shimon: Financial Interests, Personal, Other: Eli Lilly and Company; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: AstraZeneca. H. Lueck: Financial Interests, Personal, Other, Consulting Fees: Eli Lilly and Company; Financial Interests, Personal, Other, Consulting fees: AstraZeneca; Financial Interests, Personal, Other, Consulting fees: GlaxoSmithKlein; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Clovis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Eli Lilly and Company; Financial Interests, Personal, Advisory Board: Clovis. J. Beith: Other, Personal, Other: Eli Lilly and Company; Other, Personal, Advisory Board: Australian Abemaciclib Advisory Board. E. Tokunaga: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eli Lilly and Company; Financial Interests, Personal, Invited Speaker: Chugai. T. Forrester: Other, Institutional, Full or part-time Employment: Eli Lilly and Company. R. McNaughton: Other, Institutional, Full or part-time Employment: Eli Lilly and Company. J. Wei: Other, Institutional, Full or part-time Employment: Eli Lilly and Company. N. Harbeck: Financial Interests, Personal, Invited Speaker: AstaZeneca; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eli Lilly and Company; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Sandoz/Hexal; Financial Interests, Personal, Invited Speaker: SeaGen. All other authors have declared no conflicts of interest.

Background

Patients (pts) with advanced melanoma that progressed on immunotherapy/targeted therapy have an unmet medical need. Spartalizumab is an anti–PD-1 humanised monoclonal antibody (mAb) that may combine effectively with novel compounds to restore anti-tumour responses in PD-1–refractory disease. This is an analysis of a phase II, randomised, 2-part, multicentre, open-PLATforM (NCT03484923) study in pts with unresectable/metastatic melanoma progressing after prior anti–PD-1/L1 therapy.

Methods

The primary endpoint was overall response rate (ORR) per RECIST v1.1; secondary endpoints included duration of response and biomarker assessments. The selection phase comprised 4 Arms combining spartalizumab with ieramilimab (anti-LAG3 mAb; Arm 1), capmatinib (Arm 2), canakinumab (Arm 3) or ribociclib (Arm 4). An adaptive design during the selection phase allowed dropping arms for futility, adding new arms, and selecting arm(s) for expansion. Bayesian methodology was used for futility and efficacy assessments at each interim analysis (IA).

Results

As of 1 Feb 2021, 175 pts were randomised; 45, 43, 43, and 44 pts in Arms 1-4, respectively. Median age was 59 y, and 57% received ≥2 prior therapies. Overall, 166/175 pts discontinued treatment, primarily due to progressive disease (65%). ORRs in Arms 1-4 were 7% (n = 3/45), 5% (2/43), 5% (2/43) and 7% (3/44), respectively. All arms crossed the specific futility probability threshold and were declared futile at previous IAs. In Arm 1, 6 pts had LAG-3+ melanoma at baseline (≥5% + tumour cells by IHC), of which 2 pts had a partial response, both ongoing for ≈23 months. Overall, grade ≥3 adverse events occurred in 59% of pts (53%, 51%, 36%, 93% in Arms 1-4, respectively). There were 14 on-treatment deaths; 5/45 in Arm 1, primarily due to melanoma progression (4/45).

Conclusions

Although all tested combinations have been declared futile, Arm 1 data suggest pts with LAG-3+ melanoma may be more likely to respond to spartalizumab + ieramilimab treatment. Consequently, Arm 1A (spartalizumab + ieramilimab) was opened and is currently recruiting pts with previously treated unresectable/metastatic LAG-3+ melanoma.

Clinical trial identification

NCT03484923.

Editorial acknowledgement

Medical writing assistance was provided by Sivanjaa Manoj (ArticulateScience), and was funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis.

Funding

Novartis.

Disclosure

C. Robert: Financial Interests, Personal, Advisory Role: BMS, Roche, Pierre Fabre, Novartis, Amgen, Sanofi, Merck, MSD, AZ. D. Schadendorf: Financial Interests, Institutional, Funding, Case money for conducting the study to institution: Novartis; Financial Interests, Institutional, Research Grant: Novartis, BMS and Amgen; Financial Interests, Personal, Other, Consulting fees: Novartis, BMS, MSD, Roche, Incyte, Array, Pierre Fabre, Pfizer, Sanofi-Genzyme, Regeneron, 4SC, InFlarX, Neracare, Ultimovacs, Sun Pharma, Philogen, Amgen, Merck-Serono, Immunocore, Sandoz-Hexal; Financial Interests, Personal, Other, Honoraria: Novartis, BMS, Pierre Fabre, Sanofi-Genzyme, Merck-Serono; Financial Interests, Personal, Other, Attending meetings & travel: Novartis, BMS, MSD, Roche, Incyte, Array, Pierre Fabre, Pfizer, Sanofi-Genzyme, Regeneron, 4SC, InFlarX, Neracare, Ultimovacs, Sun Pharma, Philogen, Amgen, Merck-Serono, Immunocore, Sandoz-Hexal; Financial Interests, Personal, Advisory Board: Novartis, BMS, MSD, Roche, Incyte, Array, Pierre Fabre, Pfizer, Sanofi-Genzyme, Regeneron, 4SC, InFlarX, Neracare, Ultimovacs, Sun Pharma, Philogen, Amgen, Merck-Serono, Immunocore, Sandoz-Hexal; Financial Interests, Personal, Leadership Role: Dermatologic Cooperative Oncology Group (DeCOG), German Cancer Society, Hilfe-Stiftung, Deutsche Hautkrebsstiftung, NVKH eV, EuMelaReg. G.V. Long: Financial Interests, Personal, Advisory Role: Aduro Biotech Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Hexel AG, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, OncoSec, Pierre Fabre, QBiotics Group Limited, Regeneron Pha; Financial Interests, Personal, Other, Lectures of own work: BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: Aduro Biotech Inc, Amgen Inc, Array Biopharma inc, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Hexel AG, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma AG, OncoSec, Pierre Fabre, QBiotics Group Limited, Regeneron Pha. P. Ascierto: Financial Interests, Personal, Research Grant: BMS, Roche Genentech, Array, Sanofi; Financial Interests, Personal, Other, Consultancy fees: BMS, Roche-Genentech, MSD, Array, Novartis, Merck Serono, Medimmune, Sun Pharma, Sanofi, Idera, Sandoz, 4SC, Italfarmaco, Pfizer, Oncosec, Takis, Lunaphore; Financial Interests, Personal, Other, Attending meetings & travel: MSD; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Array, Merck Serono, Pierre-Fabre, Incyte, Medimmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Nektar, Boehringer-Ingelheim, Eisai,; Financial Interests, Personal, Leadership Role: Executive Board of SITC, Steering committee of Society of Melanoma Research, President of Melanoma Foundation, President of Campania Society of Immunotherapy of Cancer.. F. Meier: Financial Interests, Personal, Other, travel support or/and speaker’s fees or/and advisor’s honoraria: Novartis, Roche, Pierre Fabre, MSD, BMS; Financial Interests, Personal, Research Grant: Novartis, Roche. A.A.M. van der Veldt: Financial Interests, Institutional, Other, Consultancy fees: BMS, MSD, Merck, Eisai, Pfizer, Novartis, Pierre Fabre, Roche, Sanofi, Ipsen; Financial Interests, Personal, Other, Attending meetings: Bayer, Pfizer, Roche, Novartis, Ipsen . A. Ribas: Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Other, Consulting fees: Novartis; Financial Interests, Personal, Advisory Board: Novartis. J.S. Weber: Financial Interests, Institutional, Funding: Novartis; Financial Interests, Personal, Advisory Board: Novartis, BMS, Genentech, GSK, Pfizer, Merck, AstraZeneca, Regeneron; Financial Interests, Personal, Other, Patent owner not used in this study: Biodesix. L. Stenson: Financial Interests, Personal, Full or part-time Employment: Novartis. N. Solovieff: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. A. Louveau: Financial Interests, Personal, Full or part-time Employment: Novartis. A.D. Boran: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. J.J. Grob: Financial Interests, Personal, Other, Consultancy fees: Roche, Novartis, BMS, MSD, Amgen, Pierre Fabre, Sanofi, Merck, Pfizer; Financial Interests, Personal, Other, Honoraria: Roche, Novartis, BMS, MSD, Amgen, Pierre Fabre, Sanofi, Merck, Pfizer; Financial Interests, Personal, Other, Attending meetings & travel: Roche, Novartis, BMS, MSD, Pierre Fabre,. R. Dummer: Financial Interests, Personal, Advisory Role: Novartis, MSD, BMS, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaxiVAX SA, touchIME, ; Financial Interests, Personal, Other, Honoraria: Novartis, MSD, BMS, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaxiVAX SA, touchIME. All other authors have declared no conflicts of interest.

Background

About 10-20% of hereditary breast and/or ovarian (HBOC) cancer patients undergoing germline BRCA1/2 genetic testing harbour Variants of Uncertain Significance (VUS). Poor is the knowledge about the prevalence of germline BRCA1/2 VUS in HBOC patients of Southern Italy. Our study is aimed at describing the spectrum of these variants detected in HBOC patients in order to improve the patient’s stratification with the identification of potentially high-risk BRCA variants helpful for patient clinical management.

Methods

874 breast (BC) or ovarian (OC) cancer patients, enrolled from October 2016 to April 2021 at the “Sicilian Regional Center for the Prevention, Diagnosis and Treatment of Rare and Heredo-Familial Tumors” of University Hospital Policlinico “P. Giaccone” of Palermo, were genetically tested for germline BRCA1/2 variants through Next-Generation Sequencing analysis.

Results

The screening results showed that 639 (73.1%) out of 874 patients were BRCA-wild-type, whereas 67 (7.7%) were carriers of germline BRCA1/2 VUS and 168 (19.2%) harboured germline BRCA1/2 Pathogenic/Likely Pathogenic Variants. Overall, the mutational analysis revealed the presence of 59 different VUS detected in 67 patients, 46 of which affected by BC and 21 by OC. Twenty-one (35.6%) out of 59 variants were located on BRCA1 gene, whereas 38 (64.4%) on BRCA2. We have identified six alterations in BRCA1 and two in BRCA2 with unclear interpretation of clinical significance. Familial anamnesis of a patient harbouring BRCA1-c.3367G>T suggests for this variant a potential of pathogenicity as well as the BRCA1-c.4963T>G identified in three unrelated OC patients.

Conclusions

Understanding clinical significance of germline BRCA1/2 VUS could improve the identification of potentially high-risk variants useful for clinical management of BC/OC patients and family members. Reclassifying these variants could make them useful for predictive, prognostic and preventive purposes in clinical practice.

Legal entity responsible for the study

University Hospital Policlinico “P. Giaccone” of Palermo.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Hereditary breast (BC), ovarian (OC) and pancreatic (PC) cancers are the major BRCA-associated tumours. However, some BRCA1/2-non informative patients with a strong cancer personal and/or family history need a further genetic testing through a multi-gene panel including other high- and moderate-risk susceptibility genes. In recent years, Next-Generation Sequencing has allowed to study multiple genes simultaneously, reducing analysis costs, increasing genetic data, and offering more information to patients.

Methods

Our study was aimed to evaluate if some BC, OC and PC patients should be offered multi-gene panel testing, based on well-defined criteria regarding their cancer personal and/or family history, such as early onset of cancer, occurrence of multiple tumours, and presence of two or more affected first-degree relatives. For this reason, 205 out of 915 BC, OC and PC patients, resulted BRCA1/2 non-informative and with significant cancer personal and/or family history, were genetically tested for germline pathogenic or likely pathogenic variants (PVs/LPVs) in genes different from BRCA1/2

Results

Our study revealed that 31 (15.1%) out of 205 patients harboured germline PVs/LPVs in no-BRCA genes, including PALB2, CHEK2, ATM, MUTYH, MSH2, RAD51C. In particular, we found that 11 out of 24 (45.8%) BC patients harbouring PVs/LPVs in no-BRCA genes showed a bilateral breast cancer. Interestingly, in the absence of multi-gene panel analysis, a considerable fraction (15.1%) of PVs/LPVs would have been lost in this setting of patients.

Conclusions

Providing a multi-gene panel testing to BRCA1/2-non informative BC, OC and PC patients with a strong cancer personal and/or family history could significantly increase the detection rates of germline PVs/LPVs in other cancer predisposition genes beyond BRCA1/2. The use of a multi-gene panel testing could improve the inherited cancer risk estimation and clinical management of patients and unaffected family members.

Legal entity responsible for the study

University-Hospital Policlinico \"Paolo Giaccone\", Palermo, Italy.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

The exon 11 mutations are the most frequent KIT mutations, but represent a heterogeneous subgroup in terms of biological and clinical behavior. The exact pathogenic variant (PV) type and codon location, and other biological factors, could affect the Recurrence-Free Survival and the development of an organ-selective pattern of tumor metastasis to relapse.

Methods

116 GIST patients completely resected were included in the study between January 2005 and September 2020. The association between Exon 11 PV type with RFS was evaluated. In relapsed patients, metastatic sites were described, Neutrophil–Lymphocyte Ratio (NLR) was calculated, and plasma PD-1, PD-L1, BTN3A1, and BTN2A1 levels have been measured using homemade ELISA assays not yet commercially available.

Results

Deletions (del) of the codons 557/558 showed more aggressive tumor behavior and a higher risk of recurrence compared to other exon 11 del, or duplication/insertion/SNV (7-year RFS: 48.6% vs 73.1% vs 87.9%; p<0.001). In the 557/558 population, 77.8% of relapsed GIST harbored del simultaneously involving 557 and 558 codons (mainly KIT p.W557_K558del); when 557 and 558 deletions were analyzed separately, only 22.2% showed a tumor relapse, miming the prognostic behavior of tumor carrying del outside 557/558 position. In contrast to previous findings, in relapsed patients with 557/558 del, the peritoneum is the most frequent metastatic site (72.2%). Using thresholds by ROC analysis and multivariate analysis, we found that the patients with a tumor harboring del outside 557/558 and prevalent peritoneal metastasis, had NLR significantly lower compared to the relapsed patients with other exon 11 PVs (median 2.3 vs 3.1 G/L; p=0.029), and lower baseline levels of plasma PD-1 (>7.9 ng/mL), PD-L1 (<0.65 ng/mL), and BTN3A1 (<7.4 ng/mL).

Conclusions

The result supporting the functional cross-talk between the inflammatory response, the immune microenvironment and tumor progression, also in GIST, paradigmatic model of oncogene addiction, and represent the rationale to better investigate whether other factors of clinical or biological interest could have a further impact on tumor recurrence.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Bilateral breast cancer (BBC) is generally uncommon (1-2.6% of all patients with breast cancer), but its incidence increases particularly by up to 3% in BRCA1 or BRCA2 pathogenic variant (PV) carriers. The aim of our study was to evaluate whether all BBC patients should be offered multi-gene panel testing, regardless the criteria concerning the age at diagnosis, and personal and family history of cancer established by the current guidelines.

Methods

We retrospectively collected and analyzed all clinical information of 150 BBC patients enrolled from October 2015 to April 2021, at the Sicilian Regional Center for the Prevention Diagnosis and Treatment of Rare and Heredo-Familial Tumors” of the Section of Medical Oncology of University Hospital Policlinico “P. Giaccone” of Palermo. Recruited patients have been genetically tested for germline PVs in other gene beyond BRCA1 and BRCA2 by NGS-based multi-gene panel testing.

Results

In our investigation 58 (38.6%) out of 150 BBC patients harbored germline PVs in high and intermediate-penetrance breast cancer (BC) susceptibility genes, including BRCA1, BRCA2, PTEN, PALB2, CHEK2, ATM, RAD51C. Twenty-two out of 58 positively tested patients harbored a PV in a known BC susceptibility gene (no-BRCA). Interestingly, a noteworthy correlation between PVs in PALB2 or CHEK2 and BBCs was observed. In addition, our study showed that CHEK2 PVs are correlated with a luminal A/B phenotype and ATM PVs with a luminal B subtype. In conclusion, we found that, in the absence of an analysis performed via multi-gene panel, a significant proportion (14.7%) of PVs in genes different from BRCA1/2 would have been lost.

Conclusions

Our investigation led us to hypothesize that a deeper genetic analysis, through NGS-based multi-gene panel testing, could increase the detection rates of germline alterations in BBC patients. Particularly, in the near future, the evaluation of PVs could help to identify family members with a greater risk of developing BC (or other tumors) and consequently implement prevention and surveillance programs for these subjects.

Legal entity responsible for the study

University-Hospital Policlinico \"Paolo Giaccone\", Palermo, Italy.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Immunomodulation has emerged as an active therapeutic option in some solid tumors; however, the efficacy of immunotherapy-based regimens is limited in sarcomas or restricted to a few specific subtypes. IMMUNOSARC was a phase Ib/II trial testing the double inhibition of angiogenesis (sunitinib) and PD-1/PD-L1 axis (nivolumab) in bone and soft-tissue sarcoma (STS). In this latter cohort, the trial met its primary endpoint, with 48% of patients free of progression at 6 months (m). We present here, part of the correlative studies associated with the STS cohort.

Methods

Paraffin tumor blocks were prospectively collected at baseline (before sunitinib initiation). Direct transcriptomics was performed using HTG Molecular Oncology Biomarker panel (HTG Molecular Diagnostics, Inc.; Tucson, AZ, USA). Differential gene expression was analyzed accordingly to 6-m progression-free survival (PFS).

Results

Among the 65 STS patients enrolled in the trial, 61 samples at baseline were used for this analysis. Of 2,549 transcripts analyzed, 369 genes were significantly and differently overexpressed according to 6-m PFS: 192 and 177 genes were associated with better or worse outcome, respectively. Gene ontology (GO) analysis showed that genes associated with worse PFS were related with biological processes, such as DNA metabolism (GO:0006259; combined score (CS): 771.10, p<0.001), DNA repair (GO:0006281; CS: 292.93, p<0.001), cellular response to DNA damage (GO:0006974; CS: 231.39, p<0.001), or positive regulation of cell cycle (GO:0090068; CS: 512.62, p<0.001). On the other hand, genes associated with a PFS >6-m were related with GO biological processes such as cellular response to cytokine stimulus (GO:0071345; CS: 160.05, p<0.001) or cytokine-mediated signaling (GO:0019221; CS: 134.90, p<001).

Conclusions

DNA damage repair (DDR) and cell cycle-related processes seemed to be associated with worse outcome to immunotherapy-based schemes. Further studies are warranted to understand the potential added value of cell cycle inhibitors or DDR-targeted therapies to immunotherapy.

Clinical trial identification

NCT03277924.

Legal entity responsible for the study

J. Martín-Broto.

Funding

Sarcoma Foundation of America - SFA.

Disclosure

D. Moura: Financial Interests, Personal, Other: Pfizer. N. Hindi: Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Sponsor/Funding: Eli Lilly; Financial Interests, Institutional, Sponsor/Funding: AROG; Financial Interests, Institutional, Sponsor/Funding: Bayer; Financial Interests, Institutional, Sponsor/Funding: Eisai; Financial Interests, Institutional, Sponsor/Funding: Lixte ; Financial Interests, Institutional, Sponsor/Funding: Karyopharm; Financial Interests, Institutional, Sponsor/Funding: Deciphera; Financial Interests, Institutional, Sponsor/Funding: GSK; Financial Interests, Institutional, Sponsor/Funding: Novartis; Financial Interests, Institutional, Sponsor/Funding: Blueprint; Financial Interests, Institutional, Sponsor/Funding: Nektar; Financial Interests, Institutional, Sponsor/Funding: Forma; Financial Interests, Institutional, Sponsor/Funding: Amgen; Financial Interests, Institutional, Sponsor/Funding: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Other: PharmaMar. G. Grignani: Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Personal, Other: PharmaMar; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Bayer; Financial Interests, Personal, Other: Eisai. A. Redondo: Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Personal, Other: PharmaMar; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Tesaro; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Other: Roche; Financial Interests, Institutional, Research Grant: Eisai. S. Stacchiotti: Financial Interests, Personal and Institutional, Other: Bayer; Financial Interests, Personal and Institutional, Other: Lilly; Financial Interests, Personal and Institutional, Other: PharmaMar; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer. J.A. Lopez-Martin: Financial Interests, Personal, Other: PharmaMar; Financial Interests, Personal, Other: Eli Lilly; Financial Interests, Personal, Other: Bayer; Financial Interests, Personal, Other: Eisai; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: BMS; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Celgene; Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Other: Chobani. J. Martin Broto: Financial Interests, Personal, Expert Testimony, Honoraria: Lilly; Financial Interests, Personal, Expert Testimony, Honoraria: PharmaMar; Financial Interests, Personal, Expert Testimony, Honoraria: Eisai; Financial Interests, Personal, Expert Testimony, Honoraria: Bayer; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Institutional, Invited Speaker: PharmaMar; Financial Interests, Institutional, Invited Speaker: Eisai; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: IMMIX Biopharma; Financial Interests, Institutional, Invited Speaker: Lixte; Financial Interests, Institutional, Invited Speaker: Karyopharm; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Invited Speaker: Celgene; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Blueprint; Financial Interests, Institutional, Invited Speaker: Deciphera; Financial Interests, Institutional, Invited Speaker: Nektar; Financial Interests, Institutional, Invited Speaker: Forma; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Arog; Financial Interests, Institutional, Invited Speaker: Adaptimmune; Financial Interests, Institutional, Invited Speaker: GSK. All other authors have declared no conflicts of interest.

Background

Cancer patients are at increased risk of developing severe COVID-19 disease. Possible side effects of systemic therapy and the lack of clinical data on safety and efficacy of COVID-19 vaccination in cancer patients cause uncertainty regarding the vaccination. Here, we evaluated attitude towards and effects of COVID-19 vaccination in patients with breast or gynecological cancer. The aim was to improve counseling of our patients in clinical routine.

Methods

Since March 15^th 2021, patients who received one of the approved COVID-19 vaccines were routinely interviewed about immediate (0-2 days) and late side effects (within two weeks after vaccination). Clinical parameters such as current therapy, time interval between therapy administration and vaccination, and changes in the therapy schedule due to the vaccination were documented. Furthermore, the willingness of non-vaccinated patients to be vaccinated was assessed. The collected data were anonymously analyzed as a part of routine quality assurance.

Results

By May 10^th 2021, 111 out of 217 (51.1%) interviewed patients had received at least one shot of COVID-19 vaccine and 21 patients both shots. More than half of the vaccinated patients were >55y (60.2%; mean: 60.7y, range 30-92y); 69% with UICC/ FIGO stage III/IV cancer. 74.6% received Conmirnaty (BioNTech/ Pfizer), 18.9% Vaxzevria (AstraZeneca) and 6.5% Covid-19 Vaccine Moderna. After the first shot, 33.3% of the patients described no side effects, 49.1% reported a local reaction (swelling or pain), 23.4% flu-like symptoms, 10.8% headache and 3.6% nausea. 11 patients had symptoms that lasted longer than two days. In 11 cases, COVID-19 vaccination had an impact on delivery of the systemic therapy (n=10 postponements of therapy and n=1 dose reduction). 61.3% of the non-vaccinated patients (in total n=118) were already registered to get vaccinated; 32.8% chose to postpone vaccination for personal reasons; 5% refused vaccination.

Conclusions

Breast and gynecological cancer patients appear to tolerate COVID-19 vaccination well under systemic therapy and only in few cases the vaccination interfered with the treatment schedule. Updated results will be presented at the ESMO Congress.

Legal entity responsible for the study

LMU University Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

During COVID pandemic, many cancer patients (pts) refused to come to hospital, suspending therapies, with ominous consequences. Based on positive (+) results of DOMONCOVID, our homecare project for COVID+ cancer pts, we created a new model of assistance, ONCOHOME, delivering cancer care at home to immune-compromised pts. We aim to provide data on feasibility, efficacy and costs of this innovative model.

Methods

ONCOHOME is a multicenter project involving 3 Cancer Center (CC) of the North of Italy: National Cancer Institute, San Raffaele in Milan and Cremona CC. We created an organizational homecare model based on a medical and nursing team with a car equipped for home visits and a secretariat managing patient calls, with a dedicated phone number. The team administers cancer care at home and provides pts with the same assistance usually delivered in hospital. Patient-reported outcome (PRO) assessment is performed.

Results

From August 3^rd 2020 to May 5^th 2021, 79 cancer pts were assisted at home by Cremona team, receiving oral (62 pts), subcutaneous (10pts) or intravenous therapy (7 pts). All types of cancer were included. 77% of pts had a metastatic disease, 88% had a PS ECOG 0-1. Median duration of assistance was 126 days [range 2-270 days]. Most of the pts received oral chemotherapy (41pts). TKIs (25 pts), hormonal therapy (12 pts), supportive care with denosumab and zolendronic acid (5 pts ) and immunotherapy (1 patient, pt) were successfully administered at home, too. 13 pts required hospitalization due to clinical complications. In this group, only 2 pts were admitted to hospital due to severe toxicity; in particular, 1 pt treated with trifluridin/tipiracil developed febrile neutropenia and 1 pt treated with gefitinib reported Grade 3 diarrhea. Both pts were discharged and continued to be assisted at home.

Conclusions

ONCOHOME showed that inpatient or outpatient cancer drug administration could be successfully replaced by home administration, for appropriate therapies and selected pts. This model is feasible at an affordable cost. The project is ongoing, planning to accrue other 100 pts for each center. ONCOHOME will be implemented with electronic devices for PRO evaluation, certified telemedicine service and non-invasive wearable smart tissue monitoring physiological parameters devices.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

ML-3 and -7 demonstrated a significant OS benefit and maintenance/improvement of QOL with RIB + ET vs ET in pts with HR+/HER2− ABC. We evaluated the association of QOL with OS in ML-3 and -7.

Methods

In ML-3, postmenopausal pts were treated with RIB + fulvestrant (FUL) or FUL alone. This analysis included the NSAI cohort of ML-7, in which peri/premenopausal pts were treated with RIB + NSAI or NSAI alone. QOL was assessed with EORTC QLQ-C30. A responder analysis was performed based on published minimal clinically important differences in change from baseline to group pts as improvers/maintainers (responder) or non-improvers/non-maintainers (non-responder). The percentage of responders was summarized for each visit by treatment arm for pts who lived longer and pts who lived shorter (OS cutoffs: 39.2 mo for ML-3; 33.1 mo for ML-7).

Results

In ML-3 and -7, a greater percentage of pts living longer vs shorter had improved/maintained global health status (GHS), pain, fatigue, and diarrhea in either treatment (tx) group. In ML-7, a GHS benefit was seen for RIB vs PBO in pts living longer or shorter, with a greater benefit in pts living longer (Table). In ML-3, a tx benefit for RIB vs PBO in GHS was seen in pts living longer but was not observed in those living shorter; this trend was seen regardless of line of tx. There was a consistent benefit for RIB vs PBO for pain, fatigue, and diarrhea in ML-7 in pts living longer or shorter. In ML-3, a tx benefit was seen for RIB vs PBO for pain and diarrhea but was mainly in the second-line population for pts living longer. Table: 233P

Conclusions

In ML-3 and -7, pts living longer vs living shorter had more improved/maintained QOL over the course of tx. In both trials, RIB was generally associated with a greater percentage of pts with improvement/maintenance of GHS compared with ET alone, with greater tx benefit in pts living longer.

Clinical trial identification

MONALEESA-3; NCT02422615; MONALEESA-7; NCT02278120.

Editorial acknowledgement

Medical editorial assistance was provided by Casey Nielsen, PhD, of MediTech Media, and was financially supported by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

P.A. Fasching: Financial Interests, Personal, Advisory Board: Novartis, Roche, Pfizer, Celgene, Merck Sharp & Dohme, Macrogenics, Eisai, Puma, Lilly, AstraZeneca; Financial Interests, Personal, Other, Steering Board: Novartis; Financial Interests, Institutional, Research Grant: BioNTech, Novartis, Cepheid; Financial Interests, Personal, Invited Speaker, Lectures: Daiichi Sankyo, Merck Sharp & Dohme, Lilly. N. Harbeck: Financial Interests, Personal, Other, Consulting: Novartis, Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, MSD, Pierre Fabre, Roche, Sandoz/Hexal, Seattle Genetics; Financial Interests, Personal, Invited Speaker, Lectures: Novartis, Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, MSD, Pierre Fabre, Roche, Sandoz/Hexal, Seattle Genetics; Non-Financial Interests, Institutional, Member of the Board of Directors, Co-Director WSG: West German Study Group. G. Jerusalem: Financial Interests, Institutional, Research Grant: Novartis, Roche, Pfizer; Financial Interests, Personal, Other, not specified: Novartis, Roche, Pfizer, Lilly, Amgen, BMS, AstraZeneca, AbbVie, Daiichi Sankyo; Non-Financial Interests, Personal and Institutional, Other, not specified: Novartis, Roche, Pfizer, Lilly, Amgen, BMS, AstraZeneca, MedImmune, MerckKGA. M. De Laurentiis: Financial Interests, Personal, Invited Speaker, Honoraria: Pfizer, Novartis, Roche, AstraZeneca, Eli Lilly, Pierre Fabre; Financial Interests, Personal, Advisory Board, Honoraria: Pfizer, Novartis, Roche, AstraZeneca, Eli Lilly, Pierre Fabre. D. Tripathy: Financial Interests, Personal, Other, Consulting Fees: Novartis, Pfizer, GlaxoSmithKline, Polyphor, Sellas Life Sciences Group, Exact Sciences, Immunomedics; Financial Interests, Institutional, Research Grant, Contracted research and clinical research support: Novartis, Polyphor; Financial Interests, Personal, Other, Steering Committee: Pfizer, OncoPep; Non-Financial Interests, Personal, Advisory Board, Scientific Advisory Board (unpaid): Puma Biotechnology; Financial Interests, Personal, Invited Speaker, Fees for Lectures (educational): AstraZeneca. M. Martin: Financial Interests, Personal, Invited Speaker, Honoraria: Lilly, Pfizer; Financial Interests, Personal, Advisory Board, Honoraria: Lilly, Pfizer, AstraZeneca, Novartis, Roche-Genentech, GloxoSmithKline, PharmaMar, Taiho Oncology; Financial Interests, Institutional, Research Grant: Novartis, Roche-Genentech. D. Yardley: Financial Interests, Personal, Other, Consulting or advisory role (institution): Biotheranostics, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Eisai, Genetech, Roche, NanoString Technologies, Novartis; Financial Interests, Institutional, Research Grant, Research funding (institution): Daiichi Sankyo, Lilly, Eisai, Novartis, AbbVie, AstraZeneca, Clovis Oncology, Immunomedics, InventisBio, Lilly, MedImmune, Medivation, Merck, Oncothyreon, Pfizer, Syndax, Tesaro; Financial Interests, Personal and Institutional, Other, Travel, accommodations, expenses: Genentech, Roche, Novartis; Financial Interests, Personal, Speaker’s Bureau: Genentech, Roche, Novartis. P. Wheatley-Price: Financial Interests, Personal, Advisory Board, Lung Cancer Advisory Board: Roche, AbbVie, Takeda, Merck, BMS, Novartis, AstraZeneca, . A. Chan: Financial Interests, Personal, Invited Speaker, Honoraria: Amgen, Eisai, Novartis; Financial Interests, Personal, Other, Travel, accommodations, expenses: Amgen; Financial Interests, Institutional, Research Grant, Research funding: Eisai; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Speaker’s Bureau: Prime Oncology. R. Villanueva Vazquez: Financial Interests, Personal, Invited Speaker, Honoraria: Novartis, Pfizer, Roche. A. Nusch: Financial Interests, Personal and Institutional, Advisory Role, Consulting/Advisory role: Novartis, Amgen; Financial Interests, Personal and Institutional, Other, Travel, accommodation, expenses: Novartis; Financial Interests, Institutional, Funding, Research funding: Novartis. E. Gu, H. Hu, A. Thuerigen: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis; Financial Interests, Personal and Institutional, Stocks/Shares: Novartis. P. Pathak: Financial Interests, Personal and Institutional, Full or part-time Employment: Novartis. A. Bardia: Financial Interests, Institutional, Research Grant: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, Mersana, Innocrin; Financial Interests, Personal, Advisory Board, Advisory Board/Consulting: Biothernostics Inc., Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Spectrum Pharma, Taiho, Sanofi, Daiichi Pharma, Puma; Financial Interests, Institutional, Advisory Role, Consulting: Biothernostics Inc.; Financial Interests, Personal, Leadership Role, Steering Committee: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics; Financial Interests, Personal, Other, Travel support: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Spectrum Pharma, Taiho, Sanofi. All other authors have declared no conflicts of interest.

Background

Cancer patients (pts) have higher risk of serious COVID-19 symptoms, morbidity and mortality than general population. SARS-CoV-2 vaccine trials excluded patients with metastatic cancer or undergoing immunosuppressive therapies; therefore, the effectiveness of vaccines are unknown in this population. Hence, there is an urgent need to understand the correlation between cancer type, its treatment and vaccine efficacy.

Trial design

Methods: This is a prospective study conducted by the Oncology Unit of Cremona (Cr) Hospital, enrolling pts from Oncology, Hematology, Radiotherapy (RT) and Palliative Care divisions. The trial aims to evaluate effectiveness of mRNA vaccines [BNT162b2 (Pfizer) and mRNA-1273 (Moderna)], incidence of symptomatic COVID-19 infection, antibodies (Abs) response and onset of adverse events (AEs) in a consecutive population of 300 cancer pts, undergoing antiblastic therapies, starting from March 2021. A vaccination point was set up by Cr Hospital, dedicated to cancer pts treated with chemotherapy (CT), TKIs, RT, hormones. Only pts in follow-up or treated with adjuvant hormone are excluded. CT was suspended at least 5 days before and 3 days after vaccination; targeted therapy, immunotherapy and RT are not interrupted. Primary endpoint: Number of symptomatic pts affected by COVID-19, diagnosed 7-60 days after the 2^nddose of vaccines. The infection is defined according to the FDA criteria combined with a positive nasopharyngeal swab. Secondary endpoints: Abs variation at different timepoints compared to baseline; vaccine-related adverse events; duration of abs, up to 12 months after 2^nd dose; correlation between effectiveness of vaccines and antiblastic treatments, tumor burden, PS ECOG. Statistical analysis: The primary objective will be tested by non-inferiority one-single proportion test, compared with the value of 95% observed in the vaccine registration trials. The hypothesis of vaccine inferiority in the trial population is rejected if a rate of protection conferred by the vaccine is observed in 89% of the sample size. Results Preliminary results will be available in July 2021.

Clinical trial identification

NCT04878796.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

HER2+ BC is associated with a high incidence (up to 50%) of brain metastasis (BM) despite advances in treatment (Freedman et al. J Clin Oncol. 2019). Although several agents have been studied in patients (pts) with HER2+ BC with BM, an unmet medical need remains due to the poor prognosis in this pt population. In DESTINY-Breast01, T-DXd demonstrated efficacy in the overall population and preliminary efficacy in a pt subgroup with stable BM, with a confirmed objective response rate (ORR) of 61.4% and an extracranial confirmed ORR by independent central review (ICR) of 58.3%, respectively, median progression-free survival (PFS) of 19.4 and 18.1 mo, respectively, and median duration of response (DOR) of 20.8 and 16.9 mo, respectively (Modi S et al. Cancer Res. 2021. Abst PD3-06; Jerusalem et al. Ann Oncol. 2020. Abst 138O). Here we describe a trial evaluating T-DXd in pts ± BM with previously treated advanced/metastatic HER2+ BC.

Trial design

DESTINY-Breast12 (NCT04739761) is an open-label, multicenter, international (86 sites in the US, Europe, Australia, and Japan), phase 3b/4 study assessing the efficacy and safety of T-DXd 5.4 mg/kg q3w in pts with HER2+ BC ± BM. Pts will be enrolled in 1 of 2 cohorts (250 pts each): cohort 1 (−BM at baseline) and cohort 2 (+BM at baseline). Pts must have previously treated advanced/metastatic HER2+ BC that has progressed with ≥1 prior anti-HER2–based regimen and received ≤2 lines of therapy in the metastatic setting (excludes pts with prior tucatinib). Pts with BM must have untreated BM not needing immediate local therapy or previously treated stable or progressing BM. Primary endpoints are ORR in cohort 1 and PFS in cohort 2 (both by RECIST version 1.1 per ICR). Secondary endpoints in both cohorts are OS, DOR, time to progression, duration of subsequent therapy, PFS2, safety, and changes in symptoms, functioning, and QOL. Incidence of new symptomatic CNS metastasis (CNSM) is a secondary endpoint in cohort 1, and ORR and CNS ORR by RECIST 1.1 per ICR, CNS PFS and DOR, and time to new CNSM are secondary endpoints in cohort 2.

Clinical trial identification

NCT04739761.

Editorial acknowledgement

Medical editorial assistance was provided by ArticulateScience LLC, and funded by AstraZeneca Pharmaceuticals LP.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

N.U. Lin: Financial Interests, Institutional, Other, All support for the present manuscript/abstract (e.g., funding, provision of study materials, medical writing, article processing charges, etc.): AstraZeneca; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Zion Pharmaceuticals; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Role: Prelude Therapeutics; Financial Interests, Personal, Advisory Role: Denali Therapeutics; Financial Interests, Personal, Advisory Role: Olema Pharma; Financial Interests, Personal, Advisory Role: Aleta Bio. E. Ciruelos: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Role: Celgene. G. Jerusalem: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Lilly; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MedImmune; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: AbbVie; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Pfizer. V. Müller: Non-Financial Interests, Personal, Other, Writing support: AstraZeneca; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Seagen; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Personal, Advisory Role: Genomic Health; Financial Interests, Personal, Advisory Role: Hexal; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: ClinSol; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Tesaro; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Nektar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Teva; Financial Interests, Personal, Invited Speaker: Seattle Genetics; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche; Financial Interests, Personal, Invited Speaker, Support for attending meetings and/or travel: Pfizer; Financial Interests, Personal, Invited Speaker, Support for attending meetings and/or travel: Daiichi Sankyo; Financial Interests, Institutional, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Novartis; Financial Interests, Institutional, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Roche; Financial Interests, Institutional, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Seagen; Financial Interests, Institutional, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Genentech. N. Niikura: Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Kyowa-Kirin; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Nippon; Financial Interests, Personal, Invited Speaker: Mediphysics; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Tiho; Financial Interests, Personal, Invited Speaker: Nippon Kayaku; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MSD. G. Viale: Financial Interests, Institutional, Research Grant: Ventana; Financial Interests, Institutional, Research Grant: Cepheid; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Advisory Role: Dako/Agilent; Financial Interests, Personal, Advisory Role: Menarini; Financial Interests, Personal, Advisory Role: Medscape; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche/Genentech; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Daiichi Sankyo; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Pfizer; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Ventana; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Novartis; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Roche; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: MSD Oncology; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca. E. Oscroft, S. Anand: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. G. Walker: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca. N. Harbeck: Financial Interests, Institutional, Other, All support for the abstract: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: SeaGen; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Lilly; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: MSD; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Pierre Fabre; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Pfizer; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: SeaGen; Financial Interests, Personal, Other, Co-Director: WSG.