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For primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC.We combined four TNBC NAC patient cohorts who did not achieve pCR. RD TILs were investigated for associations with recurrence-free survival (RFS), and overall survival (OS) using Cox models with stromal TILs as a continuous variable (per 10% increment). The likelihood ratio test was used to evaluate added prognostic value of RD TILs.A total of 375 RD TNBC samples were evaluable for TILs and RCB. The median age was 50 years, with 62% receiving anthracycline/taxane chemotherapy. The RCB class after NAC was 11%, 50%, and 39% for I, II, and III, respectively. The median RD TIL level was 20% (IQR 10-40). There was a positive correlation between RD TIL levels and CD8+ T-cell density (ρ = 0.41). TIL levels were significantly lower with increasing post-NAC tumor (P = 0.005), nodal stage (P = 0.032), but did not differ by RCB class (P = 0.84). Higher RD TILs were significantly associated with improved RFS (HR: 0.86; 95% CI 0.79-0.92; P 0.001), and improved OS (HR: 0.87; 95% CI 0.80-0.94; P 0.001), and remained significant predictors in multivariate analysis (RFS P = 0.032; OS P = 0.038 for OS). RD TILs added significant prognostic value to multivariate models including RCB class (P 0.001 for RFS; P = 0.021 for OS). The positive prognostic effect of RD TILs significantly differed by RCB class for RFS (PInt=0.003) and OS (PInt=0.008) with a greater magnitude of positive effect observed for RCB class II than class III.TIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class, particularly in RCB class II.

Background The role of the adaptive immune response in tumors has been widely explored.TILs are related with a better survival in several tumors. In ephitelial ovarian cancer (EOC) there are few data focusing on the effects of neoadjuvant chemotherapy (NACT) on T-cell infiltration, with controversial results.TILs may represent a prognostic and predictive biomarker and may have a role in selecting patients for immunotherapy. Methods We retrospectively evaluated 131 patients with stage IIIC-IV EOC who received NACT with platinum and taxane, interval debulking surgery (IDS) and chemotherapy post IDS.14 patients were excluded due to complete response. Stromal and Intratumoral TILs (sTILs-iTILs) were evaluated in tumor biopsies (pre NACT samples) and on residual disease post surgery (post NACT samples), using the criteria defined by the International TILs Working Group. The objective of the study was evaluating whether NACT could determine an increase T-cell infiltration with a consequent positive effect on outcome. Results Median follow up was 70.25 months.OS at 2 and 5 years were 68.6% (95%CI: 61.0%-77.1%) and 26.8% (95%CI:19.5%-36.8%) respectively.In the final analysis 50 patients were excluded due to the lack of suitable pre NACT samples.There was no association between sTILS or iTILs values assessed on pre and/or post NACT samples with OS (HR = 0.99; HR = 1.01 respectively) and PFS (HR = 0.99; HR = 1.002 respectively). However, investigating the difference of sTILs between post (median 12; IQR 6-20) and pre NACT samples (median 7; IQR 3.25-17), we found that an increase in sTILs in post NACT compared to pre NACT samples was associated with reduced mortality risk (HR = 0.71; 95% CI: 0.50-1.00 p = 0.05).Furthermore a no-linear association between the difference between post and preNACT iTILs and OS was detected (p = 0.11). Conclusions These findings, although limited by the small sample size and the retrospective nature of this analysis, suggest a possible role of TILs detected in residual tumor after NACT as prognostic biomarker in EOC. Further data are needed in order to confirm the role of TILs after NACT and their possible relevance to predict efficacy of immunotherapeutic strategies in this setting. Legal entity responsible for the study Nicoletta Colombo, Sara Giovannoni. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Nivolumab is an established treatment for recurrent/metastatic (RM) head and neck squamous cell carcinoma (HNSCC) patients (pts) failing platinum-based treatment. However, knowledge about safety and activity data are limited to pts enrolled into clinical trial leading to drug approval. Methods We conducted a single-arm, open-label, multicentre prospective phase IIIb clinical trial with nivolumab 240 mg in subjects with RM HNSCC. Primary objective was to assess the incidence of high-grade (CTCAE v 4.03 grade 3 or higher), treatment-related (TR), selected adverse events (AE); secondary objectives were to characterize the outcome of all AE in terms of duration, time to event onset, and event resolution. Moreover, we assessed Overall Response Rate (ORR), OS and PFS and we analysed in an exploratory way clinical and biomolecular factors associated with improved outcome. A subgroup analysis was also performed in 20 pts to define baseline immunologic profiles and their changes along the treatment. Results We enrolled 127 pts with the following characteristics: male (82%), age higher than 65 years (43%), with primary cancer in oral cavity (33%), oropharynx (31%), larynx (24%), hypopharynx (8%) or other sites (4%). Performance status was 0 in 34% and 1 in 63% pts; 27% of the pts had received 2 or more systemic lines of therapy before. Grade 3-4 TR AE happened in 11% of the pts (anemia 2%, pneumonitis and encephalitis 1%), while all-grade TR AE were 40% (fatigue 20%, hypothyroidism 8%, anemia and pruritus 6%). Median duration of grade 3-4 TR AE was 10 days (4-22) and of grade 1-2 TR AE 63 days (1-336). Median OS and PFS were 7 months (5-NR) and 2 months (1.5-2.5) and ORR 12%. Pts experiencing any TR AE had an improved OS; HR 0.459 (0.254-0.827, p = 0.0096). Analyses of stromal tumor-infiltrating lymphocytes (TILs) status and PD-L1 status (clone 28-8 Agilent) are ongoing. Conclusions In this phase IIIb trial, nivolumab confirmed the safety and efficacy profile of the registration trial. Experiencing any grade TR AE revealed to be a favorable prognostic factor, as possible expression of effective immune response. Legal entity responsible for the study GONO group. Funding Bristol Myers-Squibb. Disclosure P. Bossi: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: Angelini; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Voluntis. M.C. Merlano: Honoraria (self), consultancy or A.B.: Bristol M.S.; Honoraria (self), consultancy or A.B.: Merck S.D.; Honoraria (self), consultancy or A.B.: Merck; Shareholder / Stockholder / Stock options, Stocks: Glaxo SK; Research grant / Funding (institution), Support for clinical trials: Merck. M.G. Ghi: Honoraria (self), Advisory role: BMS; Honoraria (self), Advisory role: MSD; Honoraria (self), Advisory role: Merck Serono. G. Rinaldi: Honoraria (self), Research grant / Funding (self), Speaker and PI in clinical Trial: Novartis; Honoraria (self), Research grant / Funding (institution), Speaker and PI in clinical Trial: BMS; Research grant / Funding (self), PI in clinical Trial: MSD. F. Morelli: Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): BMS. A. Farnesi: Honoraria (self), speaker: Bayer; Honoraria (self), speaker: Novartis. D. Galizia: Honoraria (self), public speaker: BMS; Honoraria (self), congress travel costs coverage: Merck; Honoraria (self), congress travel costs coverage: Roche; Honoraria (self), congress travel costs coverage: Angelini. L.F. Licitra: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Speaker: BMS; Honoraria (self), Research grant / Funding (institution), Speaker: Eisai; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Speaker: MSD; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Speaker: Merck-Serono; Honoraria (self), Research grant / Funding (institution), Speaker: Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution), Speaker: Novartis; Honoraria (self), Research grant / Funding (institution), Speaker: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Speaker: Roche; Honoraria (self), Travel / Accommodation / Expenses, Speaker: Bayer; Honoraria (self), Travel / Accommodation / Expenses, Speaker: Debiopharm; Honoraria (self), Travel / Accommodation / Expenses, Speaker: Sobi; Honoraria (self), For teaching in medical meetings: Incyte Biosciences Italy srl; Honoraria (self), Expert opinion in advisory board meetings: Doxa Pharma srl; Honoraria (self), For public speaking in medical meetings: Amgen; Honoraria (self), Expert opinion in advisory board meetings: Nanobiotics Sa; Honoraria (self), For public speaking in medical meetings and/or expert opinion in advisory boards: GSK; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2016-2017): Celgene International; Research grant / Funding (institution), Founds to my Institution for 2 clinical trials (2014-2018): Exelixis Inc.; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2014-2015): Hoffmann-La Roche Ltd.; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2017): IRX Therapeutics, Inc.; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2016): Medpace Inc.; Research grant / Funding (institution), Founds to my Institution for a clinical trial (2014): Pfizer; Travel / Accommodation / Expenses, Travel coverage for medical meetings: Stilema, AccMed, Aiocc, Aiom. All other authors have declared no conflicts of interest.