Highlights in breast cancer

CONGRESS HIGHLIGHTS SPECIAL EDITION 309 Highlights in breast cancer W. Lybaert, MD In this article, the most important new studies presented at ESMO 2017 in Madrid in early (EBC) and metastatic breast cancer (MBC) are summarised. In EBC, 5 topics are highlighted: integration of PI3K and CDK4/6 inhibition in the neoadjuvant treatment of oestrogen receptor positive (ER+) EBC, dual endocrine blockade as adjuvant treatment in ER+ EBC, escalated adjuvant treatment in human epidermal growth factor receptor positive (HER2+) EBC and small tumours that can also show an aggressive course. In MBC, 4 topics are discussed: predicting immunogenicity in MBC, abscopal effect in MBC, confirmed benefit of PARP inhibitors in BRCA mutated MBC and CDK4/6 inhibition in first-line MBC. (BELG J ONCOL 2017;11(7):309-314) EARLY BREAST CANCER PRIMARY RESULTS OF THE LORELEI-STUDY: A PHASE II RANDOMISED, DOUBLE-BLIND STUDY OF NEOADJUVANT LETROZOLE + TASELISIB VERSUS LETROZOLE + PLACEBO IN POSTMENOPAUSAL WOMEN WITH ER+/HER2EARLY STAGE BREAST CANCER Taselisib is an oral, potent and selective PI3K inhibitor with enhanced activity against PIK3CA mutant (MUT) cancer cells. Confirmed partial responses were observed in patients (pts) with PIK3CA MUT MBC treated with taselisib as a single agent and combined with endocrine therapy. Three hundred and thirty four postmenopausal pts with ER+/HER2-, stage I-III, operable EBC and evaluable tumour tissue for centralised PIK3CA genotyping were randomised (1:1) to receive letrozole + either taselisib (4 mg five days on/ two days off) or placebo for sixteen weeks (wks), followed by surgery. Co-primary endpoints were objective response rate (ORR) by centrally assessed breast MRI and pathologic complete response (pcr, ypt0/is N0) rate at surgery, in all randomised pts and in pts with PIK3CA MUT tumours. The addition of taselisib to letrozole increased the ORR from 38% to 56.2% in the PIK3CA MUT subset (p = 0.033) and in all randomised ptsfrom 39.3% to 50% (p = 0.049). No sig- nificant difference was observed for pcr rate overall or in the PIK3CA MUT pts. The most common grade 3-4 adverse events in the taselisib arm were gastrointestinal disorders (7.8%), infections (4.8%) and skin/subcutaneous tissue disorders (4.8%). Grade 3-4 hyperglycaemia occurred in 1.2% of pts. Taselisib discontinuation (10.8%) and dose reductions (11.4%) were infrequent.1 LORELEI is the first randomised study to demonstrate a significant increase in ORR following treatment with a PI3K selective inhibitor + letrozole in patients with ER+/HER2- EBC. Comments on this study are an expected low pcr rate with only four months of endocrine therapy with or without addition of taselisib, and that the addition of taselisib added mostly toxicity on a background of increased ORR. In conclusion, pan-pi3k inhibitors are not ready for prime-time in ER+ EBC. LETROZOLE AND PALBOCICLIB VERSUS 3RD GENERATION CHEMOTHERAPY AS NEOADJUVANT TREATMENT OF LUMINAL BREAST CANCER: RESULTS OF THE PHASE II UNICANCERNEOPAL STUDY The benefit of neoadjuvant chemotherapy in pts with luminal breast cancer (LBC) is limited. Palbociclib combined with endocrine treatment has shown impressive results in Department of Medical Oncology, AZ Nikolaas Sint-Niklaas (Iridium Kankernetwerk), Sint-Niklaas, Belgium. Please send all correspondence to: W. Lybaert, MD, AZ Nikolaas Sint-Niklaas, Department of Medical Oncology, Moerlandstraat 1, 9100 SintNiklaas, Belgium, email: willem.lybaert@aznikolaas.be. Conflict of interest: The author has nothing to disclose and indicates no potential conflict of interest. Keywords: breast cancer, luminal, early breast cancer, metastatic breast cancer, PI3K, CDK4/6, neoadjuvant, HER2, immunogenicity, PARP, BRCA VO LU M E11N O V E M B E R 2 017 7

310 MBC. In this trial, postmenopausal women were eligible if they had stage II-III ER+/HER2- EBC, were not a candidate for breast conserving surgery (BCS), and had either a PAM50 luminal B, or a PAM50 luminal A profile with proven lymph node involvement (N+). A parallel 1:1 randomisation proposed six courses of 3 rd generation chemotherapy (FEC100 x3 - docetaxel 100 x3), or 19 wks of letrozole (L) 2.5 mg/day + palbociclib (P) 125 mg/day, 3 wks/4. Surgery was performed at week 20. The primary endpoint was locally assessed Residual Cancer Burden (RCB) rate. Secondary endpoints included safety, response rate, positive and negative predictive values of PAM50 ROR (risk of recurrence)-defined status, centrally reviewed RCB, and BCS rates. Out of 184 screened pts, 106 women with stage II-IIIA, PAM50-ascertained LBC were randomised. Pts had T1-2 (73%) or T3 (27%), N+ (26.5%), and luminal B (89%) tumours. Local RCB 0/I/II/III was observed in 3.8%/3.8%/52%/40.4% of pts in the LP arm, and in 5.9%/9.8%/37.3%/47.1% in the chemo arm, respectively. Central and local RCB results were identical. ROR score was not predictive of RCB 0/I. The ORR and BCS rates were 74.5% and 76%, and 69.2% and 68.6%, in the LP and chemo arms, respectively. The Ki-67 final median value was significantly lower in the LP arm (3% versus 8%). Of 19 serious adverse events, two occurred in the LP arm and seventeen in the chemo arm. 2 Neoadjuvant LP led to a slightly lower pcr/rcb 0/I rate than chemo, however clinical response and BCS rates were similar in both arms and LP had a more favourable safety profile. This is the first head-to-head comparison of endocrine therapy with a CDK4/6 inhibitor and chemotherapy. The study did not meet its primary endpoint (RBC) for letrozole + palbociclib versus chemotherapy. The challenge remains the identification of luminal EBC pts for whom an endocrine-based approach can improve the outcome, either replacing chemotherapy in intermediate-risk or as an add-on in high-risk disease. The potential of this scheme may lie in frail and elderly pts. PHASE III STUDY EVALUATING THE ADDITION OF FULVESTRANT TO ANASTROZOLE AS ADJUVANT THERAPY IN POSTMENOPAUSAL WOMEN WITH HR+/HER2- EBC: GEICAM 2006-10 Fulvestrant (F) is a selective oestrogen receptor degrader for HR+ MBC pts. This trial compares anastrozole (A) versus A in combination with F (A+F) to address the hypothesis that a complete oestrogen blockade can prevent resistance to aromatase inhibitors in the adjuvant setting. 3 This was a multicentre, open label, phase III study in which HR+/HER2- EBC postmenopausal pts were randomised 1:1 to A for five years (y) or A+F (A concurrently with F 250 mg/4 weeks for 3y followed by 2y of A). Pts were stratified for prior chemotherapy (yes/no), number of positive lymph nodes (0/1-3/ 4), HR status (both positive/one positive) and site. The primary objective was disease-free survival (DFS). In 2010, when the negative results of the FACT trial were reported, the financer decided to stop study support after the inclusion of 872 pts. Four hundred and thirty seven pts were randomised to A and 435 to A+F. Pts characteristics were well balanced between arms; median age was 62y, 46.9% were N0, 89.5% ER+/PgR+ and 68.2% had received prior chemotherapy. Treatment was completed as planned by 72.5% and 48.5% of A and A+F pts. Most relevant grade 2-3 toxicities with A versus A+F were hypertension (13.2%; 9.9%), fatigue (5.2%; 11.8%), LDL-cholesterol increase (9.4%; 5.3%), osteoporosis (5.5%; 6.9%) and musculoskeletal bone/joint pain (26.3%; 29.4%). After a median follow-up of 6.3y, the proportion of pts disease-free at 5y was 90.99% (A 90.77%, A+F 91.25%, p = 0.357); 9.4% had BC relapse (A 10.5%; A+F 8.3%) and 4.3% had secondary tumours (A 3.9%; A+F 4.6%). The medians for survival and breast cancer-specific survival were not reached. 3 This study failed to demonstrate a statistically significant increase in DFS of adding F to A as adjuvant therapy, though no formal conclusion can be extracted from this trial due to the F administered dose (250 mg) and the actual trial sample size. Inclusion of only high-risk pts with the appropriate dose of F (500 mg) is a missed opportunity to find a benefit of dual endocrine blockade. NERATINIB AFTER TRASTUZUMAB-BASED ADJUVANT THERAPY IN EARLY-STAGE HER2+ BREAST CANCER (BC): 5-YEAR ANALYSIS OF THE PHASE III EXTENET TRIAL In the Herceptin Adjuvant (HERA) trial, 24% of pts who received trastuzumab (T) for 1y had a disease recurrence at 11y of follow-up. The primary analysis of the ExteNET trial, performed after 2y of follow-up, showed that a 1y course of neratinib after T-based adjuvant therapy significantly improved the invasive disease-free survival (idfs) versus placebo in HER2+ EBC. 4 During ESMO 2017, updated 5y efficacy findings were reported. 5 ExteNET is an international, multicentre, randomised, double-blind, placebo-controlled phase III trial. Pts received oral neratinib 240 mg/day or placebo for 1y. After 2y, randomised pts were asked to reconsent to collection of data concerning disease recurrences and survival from medical records for a further 3y. The pre-planned 5y analysis was by intention-to-treat (ITT). Non-consenting pts were censored at their last physical examination. The updated 5y efficacy findings were based on 2,840 pts in the ITT pop- VOLUME11NOVEMBER2017

CONGRESS HIGHLIGHTS SPECIAL EDITION 311 ExteNET: idfs by hormone receptor status FIGURE 1. idfs in function of the hormone receptor status in the ExteNET study. 5 ulation (1,420 pts receiving neratinib and 1,420 receiving placebo). Of these, 53 pts had died during the initial 2y follow-up and 2,117 (76%) pts consented to the additional follow-up. Overall, 1,209 pts were HR-including 88.8% and 88.9% of pts in the neratinib and placebo arms, respectively. After a median follow-up of 5.2y, 2,810 pts in the ITT population demonstrated idfs rates of 90.2% with neratinib versus 87.7% with placebo (HR: 0.73, p= 0.008). The HR+ subgroup demonstrated idfs rates of 91.2% with neratinib versus 86.8% with placebo (HR: 0.60, p= 0.002); while the HR- subgroup showed idfs rates of 88.9% versus 88.8% (HR: 0.95, p= 0.762). Overall survival data are not yet mature. Neratinib was associated with a transient initial decrease in HRQoL, particularly regarding physical well being, that may have been due to neratinib-related diarrhoea. ExteNET showed a continued clinically significant benefit of neratinib, particularly in higher risk, HR+ disease (Figure 1). Diarrhoea is a limiting factor, but can be reduced significantly with prophylaxis, which is mandatory a component of treatment. There is no evidence of increased symptomatic cardiac toxicity. 5,6 NOT ALL SMALL NODE NEGATIVE (PT1A/BN0) BREAST CANCERS ARE SIMILAR: OUTCOME RESULTS FROM AN EORTC 10041/BIG 3-04 (MINDACT) TRIAL SUBSTUDY Adjuvant systemic therapy for pt1a/bn0 breast cancer is controversial, as these tumours overall have low relapse risks. The best tool to identify a subgroup that would benefit from adjuvant treatment, is unknown. This subgroup included pts with pt1a/bn0 tumours enrolled in MINDACT who had both their genomic risk G (per MammaPrint ) and clinical risk C (per a modified version Adjuvant! Online) assessed. Pts characterised as lowrisk in both assessments were spared chemotherapy (CT), while in those characterised as C&G high, CT was advised. Discordant cases were randomised to receive CT based on the C or the G result. Here, we report the 5y rates of distant metastasis-free survival (DMFS), distant metastasis-free interval (DMFI) and overall survival (OS) for pt1a/bn0 pts who received or not CT based on their G or C risk result. 7 Eight hundred and twenty six of 6,693 (12.3%) pts with pt1a/bn0 tumours were enrolled in MINDACT. Three hundred and ten of 826 (37.5%) were 60 years and 525/826 (63.6%) were postmenopausal. Five hundred and eighty five of 727 (80.5%) were invasive ductal, 662/727 (91.1%) ER+, 46/727 HER2+ (6.3%) and 81/727 (11.1%) had grade 3 tumours. IHC subtype classification identified 426/727 (58.6%) as luminal A; 193/727 (26.5%) luminal B; 38/727 (5.2%) luminal B/HER2+; 8/727 (1.1%) HER2+; 37/727 (5.1%) triple-negative tumours. Almost all pts (820/826; 99.3%) were clinical low-risk (CL). Overall, 624/826 (75.5%) were CL/GL and 196/826 (23.7%) were CL/GH (five patients were CH/GL, no cases were CH/GH, one missing). Five year VOLUME11NOVEMBER20177

312 DMFS for pts with CL/GH pt1a/bn0 tumours who received CT was 97.3% versus 91.4% for those who did not. Five year DMFI and OS for these pts treated with CT were 98.8% and 98.5% versus 91.4% and 95.8%, respectively, for those who did not receive CT. 7 Biological characteristics can be used as determinants of adjuvant CT administration for T1a/bN0 tumours. An important portion (23.7%) of these small tumours was CL and GH (MammaPrint ) risk and derived a benefit from CT. The majority of these cases were also luminal B, HER2+ or basal. Given the excellent outcome overall with or without CT, risk versus benefit of CT has to be taken into account (patient s age, performance status, comorbidities and preferences). METASTATIC BREAST CANCER RELATIONSHIP BETWEEN TUMOUR INFILTRATING LYMPHOCYTE (TIL) LEVELS AND RESPONSE TO PEMBROLIZUMAB IN METASTATIC TRIPLE NEGATIVE BREAST CANCER (TNBC): RESULTS FROM KEYNOTE-086 TILs have been observed in TNBC and are thought to represent pre-existing antitumor immunity. Thus, TILs could be a biomarker for response to immune checkpoint blockade. We assessed if TIL levels were associated with response to pembrolizumab monotherapy in the phase II KEYNOTE-086 study of previously treated mtnbc of any PD-L1 expression (cohort A) or previously untreated, PD-L1+ mtnbc (cohort B). 8 Stromal TILs were quantified by a single pathologist, blinded to clinical data using a published method of light microscopy of H&E stained slides obtained from tumour biopsies. PD-L1 expression was assessed using the PD-L1 IHC 22C3 pharmdx assay. Response was assessed every nine wks for twelve months, then every twelve wks (RECIST v1.1, central review). Relationships between transformed TIL levels and ORR and DCR (CR + PR + SD 24 wks) were assessed adjusted for cohort (A versus B) and biopsy site (lymph node versus non-lymph node). One hundred and ninety three of the first 222 pts enrolled had evaluable tumour samples: 147 from cohort A, 46 from cohort B. In total, 146 samples were newly collected (mostly from metastatic sites), 47 were archival (mostly from primary breast tumours). The median TIL level was higher in cohort B versus A (17.5% versus 5%), and in archival versus newly collected samples (10% versus 5%), and lymph node versus non-lymph node samples (10% versus 5%). The ORR in pts with TIL level versus < median was 6% versus 2% in cohort A and 39% versus 9% in cohort B. Median TIL level in responders versus non-responders was 10% versus 5% in cohort A and 50% versus 15% in cohort B. In the combined cohorts, higher TIL levels were associated with significantly improved ORR and DCR. PD-L1 expression significantly correlated with TIL levels. 8 TIL levels can identify pts with mtnbc with a greater chance of achieving response to pembrolizumab monotherapy, particularly in the first-line setting. TILs should be routinely assessed in primary tumours to stratify for trials using immunotherapy in breast cancer. ADAPTIVE PHASE II RANDOMISED NON- COMPARATIVE TRIAL OF NIVOLUMAB AFTER INDUCTION TREATMENT IN TNBC: FIRST RESULTS OF THE TONIC TRIAL Anti-PD-(L)1 can result in durable responses in pts with mtnbc. However, only a small subgroup of TNBC pts benefit from anti-pd-(l)1 with response rates of ± 10% in unselected cohorts. There is an urgent clinical need to identify strategies that render the tumour micro-environment more sensitive to anti-pd-(l)1therapy. Preclinical studies have shown that irradiation or low dose chemotherapy may stimulate anti-cancer immune responses. In this trial, 50 pts with mtnbc who received 3 lines of palliative chemotherapy were randomly allocated to one of five two week induction treatments consisting of: 1) 3x 8 Gy irradiation of 1 metastatic lesion or, 2) 2x doxorubicin 15 mg weekly or, 3) cyclophosphamide 50 mg daily orally or, 4) 2x cisplatin 40 mg/m² weekly or, 5) no induction treatment. After this two week induction period, all pts received nivolumab 3 mg/kg until RECIST 1.1 progression. To date, 50 pts are evaluable with a median follow-up of four months (range 1-15). Previous treatments for metastatic disease were 0, 1 or 2+ lines in 20%, 52% and 28%, respectively. The ORR is 22% with two CRs (4%) and nine PRs (18%). An additional two pts had a SD (4%), resulting in a clinical benefit rate (CR + PR + SD >24 wks) of 26%. The median duration of response was 10.9 months. Pts with higher leukocyte infiltration and CD8 T-cell counts in tumour biopsies were more likely to respond to the treatment. 9 This first study in TNBC shows that nivolumab after priming the tumour micro-environment with either irradiation or chemotherapy is feasible and results in a promising response rate that appears higher than in previous PD-(L)1 blockade monotherapy studies in unselected TNBC. OLYMPIAD: FURTHER EFFICACY OUTCOMES IN PATIENTS WITH HER2- MBC AND A GERMLINE BRCA MUTATION RECEIVING OLAPARIB MONOTHERAPY VERSUS STANDARD SINGLE-AGENT CHEMOTHERAPY TREATMENT OF PHYSICIAN S CHOICE Among pts with metastatic HER2- BC and a germline VOLUME11NOVEMBER2017

CONGRESS HIGHLIGHTS SPECIAL EDITION 313 FIGURE 2. PFS in the phase III MONARCH-3 trial. 12 BRCA1/2 mutation in the OlympiAD study, the ORR with olaparib was double what was seen with standard chemotherapy. The observed ORR of 59.9% with olaparib exceeded that seen in prior phase II studies, possibly owing to the previous study populations being more heavily pretreated. Importantly, the onset of response was early and similar in both treatment arms, which may be useful in symptomatic pts or in patients with rapid disease progression where a quick response is needed. Olaparib treatment also led to a larger median reduction in target lesion size compared with chemotherapy. Although the study was not powered to detect differences in treatment effects between subgroups, the PFS benefit for olaparib over chemotherapy across subgroups by metastatic location and number of metastatic sites was consistent with what was seen in the overall population. 10 The change from baseline in global health status/qol score significantly favoured pts treated with olaparib compared with chemotherapy. The time to deterioration in global health status/qol also significantly favoured pts treated with olaparib compared with chemotherapy; 64.0% of patients were deterioration-free at twelve months in the olaparib group and 53.5% in the chemotherapy. Although potentially biased by the open-label nature of the study, a longer time to subsequent cancer therapy may reflect perceived clinical benefit for pts, primarily driven by emotional and cognitive scales. 11 New trials are needed to investigate the role of PARP inhibition as consolidation treatment following chemotherapy or in combination with immunotherapy. MONARCH 3: ABEMACICLIB AS INITIAL THERAPY FOR PATIENTS WITH HR+, HER2- ADVANCED BREAST CANCER MONARCH 3 evaluates abemaciclib, an oral selective CDK4/6 inhibitor + the non-steroidal aromatase inhibitors (NSAI) anastrozole or letrozole as initial therapy for women with HR+/HER2- MBC. The study included 493 endocrine naïve pts or pts with disease relapse >12 months after (neo) adjuvant endocrine therapy and randomised them (2:1) to receive abemaciclib (150 mg, twice daily continuous schedule) or placebo, both in combination with anastrozole (1 mg daily) or letrozole (2.5 mg daily). The primary endpoint was PFS, while ORR was a key secondary objective. 12 Results of the interim analysis at 18 months showed that, compared to endocrine therapy alone, the combination of abemaciclib and endocrine therapy significantly prolonged the PFS with a hazard ratio (HR) of 0.543 (median PFS: not reached with abemaciclib vs. 14.7 months in placebo arm; p= 0.000021) (Figure 2). In pts with measurable disease, the ORR was 59% in the abemaciclib arm versus 44% in the placebo arm. The most frequent adverse events seen with abemaciclib versus placebo were diarrhoea (81.3% vs. 29.8%), neutropenia (41.3% vs. 1.9%), and fatigue (40.1% vs. 31.7%) 12. In summary, abemaciclib plus endocrine therapy demonstrated a tolerable safety profile and was an effective initial treatment for pts with HR+/HER2- MBC, significantly improving PFS and ORR. As such, abemaciclib is the third CDK4/6 inhibitor confirming the role of this new class of agents in combination with endocrine therapy in the treat- VOLUME11NOVEMBER20177

314 KEY MESSAGES FOR CLINICAL PRACTICE 1. At this moment, there is no role for pan-pi3k inhibitors in the neoadjuvant treatment of ER+, HER- EBC. 2. Combined letrozole + palbociclib is not better than chemotherapy as neoadjuvant treatment in luminal EBC. 3. There is no proven additional benefit of dual endocrine blockade in the adjuvant setting of EBC. 4. Benefit from extended treatment with neratinib in high-risk ER+, HER2+ disease is confirmed. Incremental toxicity is to be considered. No data on OS yet. 5. Small node-negative tumours can be very aggressive, even if they are classified as clinical low risk. Tumour biology needs to be taken into account when deciding on adjuvant treatments in this patient population. 6. High TILs and low LDH may predict response to immunotherapy in TNBC. 7. Priming with radiotherapy or chemotherapy followed by boost with nivolumab seems an attractive strategy in TNBC. 8. The PARP inhibitor olaparib confirmed its activity in BRCA mutated MBC. 9. Abemaciclib is the third CDK4/6 inhibitor confirming the role of this new class of agents in combination with endocrine therapy in the treatment of MBC. ment of MBC. No data on OS are available yet. Median OS on letrozole alone is now approximately 50 months. Exploratory subgroup analyses suggest that pts with liver metastases had substantial benefit from the addition of abemaciclib (twelve month PFS achieved by 61.5% versus 31.4% of pts with placebo), while in some pts with a long treatment-free interval or bone-only disease (twelve month PFS 86% versus 75.7% of pts with placebo) single agent endocrine therapy may be an appropriate initial therapy. 12 REFERENCES 1. Saura C, et al. Primary results of LORELEI: a phase II randomised, double-blind study of neoadjuvant letrozole (LET) plus taselisib versus LET plus placebo (PLA) in postmenopausal patients (pts) with ER+/HER2-negative early breast cancer (EBC). Presented at ESMO 2017; Abstract LBA10_PR. 2. Cottu P, et al. Letrozole and palbociclib versus 3 rd generation chemotherapy as neoadjuvant treatment of luminal breast cancer. Results of the UNICAN- CER-NeoPAL study. Presented at ESMO 2017; Abstract LBA9. 3. Ruíz-Borrego M, et al. Phase III evaluating the addition of fulvestrant (F) to anastrozol (A) as adjuvant therapy in postmenopausal women with hormone receptor positive HER2 negative (HR+/HER2-) early breast cancer (EBC): Results from the GEICAM/2006-10 study. Presented at ESMO 2017; Abstract 148O. 4. Chan A, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2016;17(3):367-377. 5. 149O Martin Jimenez M, et al. Neratinib after trastuzumab (T)-based adjuvant therapy in early-stage HER2+ breast cancer (BC): 5 year analysis of the phase III ExteNET trial. 6. Delaloge S, et al. Effects of neratinib (N) on health-related quality of life (HRQoL) in early-stage HER2+ breast cancer (BC): longitudinal analyses from the phase III ExteNET trial. Presented at ESMO 2017; Abstract 177P. 7. 150O_PR Tryfonidis K, et al. Not all small node negative (pt1abn0) breast cancers are similar: Outcome results from an EORTC 10041/BIG 3-04 (MINDACT) trial substudy. 8. Loi S, et al. Relationship between tumour infiltrating lymphocyte (TIL) levels and response to pembrolizumab (pembro) in metastatic triple-negative breast cancer (mtnbc): results from KEYNOTE-086. Presented at ESMO 2017; Abstract LBA13. 9. Kok M, et al. Adaptive phase II randomised non-comparative trial of nivolumab after induction treatment in triple negative breast cancer: TONIC-trial. Presented at ESMO 2017; Abstract LBA14. 10. Delaloge S, et al. OlympiAD: Further efficacy outcomes in patients with HER2-negative metastatic breast cancer and a germline BRCA mutation receiving olaparib monotherapy versus standard single-agent chemotherapy treatment of physician s choice. Presented at ESMO 2017; Abstract 243PD. 11. Robson M, et al. OlympiAD: Health-related quality of life (HRQoL) in patients with HER2-negative metastatic breast cancer (mbc) and a germline BRCA mutation (gbrcam) receiving olaparib monotherapy versus standard single-agent chemotherapy treatment of physician s choice (TPC). Presented at ESMO 2017; Abstract 290P. 12. Di Leo A, et al. MONARCH 3: Abemaciclib as initial therapy for patients with HR+/ HER2- advanced breast cancer. Presented at ESMO 2017; Abstract 236O_PR. VOLUME11NOVEMBER2017