Background

Neoantigens derived from tumor-associated mutations can elicit T cell-mediated antitumor immunity and facilitate tumor rejection. Here, we assessed the safety and efficacy of personalized neoantigen peptide vaccination (PPV) in advanced NSCLC patients who had failed conventional therapy.

Methods

24 stage III/IV recurrent NSCLC patients were immunized with mixtures of short and long neoantigen peptides based on personalized tumor-associated mutations and predicted HLA peptide binding affinities. Primary study endpoints were feasibility and safety. Secondary endpoints were PPV-induced immune responses, progression-free survival (PFS) and overall survival (OS).

Results

Aside from transient rash, fatigue and/or fever in 3 patients, no treatment-related adverse events were observed. The median PFS and OS of the 24 PPV patients was 6.0 and 8.9 months, respectively. Of the 16 PPV patients bearing EGFR mutations, 7 experienced objective tumor response by RECIST 1.1, including 6 PR and 1 CR. Of the 8 patients expressing wild-type EGFR, 4 showed SD and no PR or CR. Importantly, 9 PPV patients who continued EGFR inhibitor (EGFRi) therapy in spite of prior progression showed extended survival compared to 7 patients who stopped EGFRi prior to initiating PPV (median OS: 13.8 vs. 7.6 months, P = 0.038), though both patient groups experienced similar objective response rates. Immune monitoring demonstrated the immunogenicity of two highly shared EGFR mutations in multiple responding patients. Robust PPV-specific immune responses were observed in 4 responding patients, with ELISPOT and tetramer staining showing incremental increases in peripheral blood neoantigen-specific CD8+ T cell frequencies for up to 3 months during PPV. T-cell receptor (TCR) Vb sequencing also demonstrated significantly increased frequencies of neoantigen-specific CD8⁺ TCR clones in both peripheral blood and tumor-infiltrating lymphocytes following PPV.

Conclusions

These results suggest that PPV is safe and potentially beneficial for advanced stage EGFR-mutated NSCLC patients. Survival analyses imply that PPV in combination with EGFRi may be a viable treatment option for NSCLC, in spite of prior EGFRi failure.

Clinical trial identification

ChiCTR-INR-16009867.

Legal entity responsible for the study

Tianjin Beichen Hospital.

Funding

Tianjin HengJia Biotechnology Development Co., Ltd.

Disclosure

F. Li: Shareholder / Stockholder / Stock options: Tianjin HengJia Biotechnology Development Co., Ltd. G. Lizee: Advisory / Consultancy: HengJia Neoantigen Biotechnology (Tianjin) Co., Ltd. P. Hwu: Advisory / Consultancy: Dragonfly Therapeutics; Advisory / Consultancy: GlaxoSmithKline; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Immatics; Advisory / Consultancy: Sanofi; Research grant / Funding (institution): Genentech. L. Deng: Full / Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd. Q. Zou: Full / Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd. M.A. Stairs: Advisory / Consultancy: HengJia Neoantigen Biotechnology (Tianjin) Co., Ltd. C. Chen: Full / Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd. C. Huo: Full / Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd. Y. Wang: Full / Part-time employment: Tianjin HengJia Biotechnology Development Co., Ltd. All other authors have declared no conflicts of interest.

Background

Since the introduction of immune-checkpoint blockade, the overall survival has significantly improved for patients with advanced melanoma. However, to date, there is limited data on patients’ functioning and health-related quality of life (HRQoL), years after active treatment. Therefore, we evaluated these outcomes in advanced melanoma survivors (AMS) and compared these with matched controls.

Methods

Ipilimumab-treated AMS without systemic treatment for at least 2 years were recruited from 15 hospitals. The primary outcome was HRQoL assessed with the European Organization for Research and Treatment of Cancer quality of life questionnaire-C30 (QLQ-C30). Secondary outcomes were fatigue, anxiety, depression and disease specific HRQoL. Up to 5 controls per AMS were individually matched on age, gender and educational status. Survivors and controls were compared on QLQ-C30 scores using generalized estimating equations. Differences in QLQ-C30 scores were classified as clinically important according to published guidelines.

Results

A total of 89 AMS were evaluated in this study. After last administration of ipilimumab, the mean follow-up (FU) was 45.5 (SD 20.8) months. Comparison with matched controls showed that AMS scored significantly lower on physical (difference (diff) = -5.80, p=.005), role (diff =-5.97, p=.02), cognitive (diff = -8.05, p=.001), and social functioning (diff = -8.49, p = <.001) and higher in symptom burden of fatigue (diff =7.48, p=.004), dyspnea (diff = 6.47, p=.02), diarrhea (diff = 3.78, p=.04) and financial impact (diff = 8.07, p=.001). Comparison between AMS with a FU ≥ 36 and FU < 36 months showed that social functioning, global QoL and financial impact scores were higher among the longer term survivors. Group differences in both analyses were clinically relevant.

Conclusions

Compared to matched controls, AMS showed overall worse functioning scores and more symptoms of fatigue, dyspnea, diarrhea and financial impact. AMS with a longer FU reported better QoL, but more financial issues. These study results may help to develop interventions to the individual healthcare needs of AMS and contribute to the development of appropriate survivorship care.

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

Bristol-Myers Squibb.

Disclosure

All authors have declared no conflicts of interest.

Background

MET signaling has a role in gliomagenesis and glioma stem cell maintenance and midkine (ALK ligand) promotes resistance of glioma cells to anticancer therapies. Crizotinib is an ALK and c-MET inhibitor with a preclinical rationale to be tested in newly diagnosed GB.

Methods

Elegible patients received crizotinib in addition to standard RT and TMZ and then adjuvant TMZ. Maintenance treatment with crizotinib beyond 6 TMZ cycles was allowed. The primary objective was safety evaluation. Secondary objectives included efficacy (progression free survival (PFS) and overall survival (OS)) and an exploratory biomarker analysis. PFS and OS were estimated with Kaplan–Meier method. The results of the dose-escalation cohort (DE) have been reported previously. 250 mg/d was the crizotinib dose selected for the expansion cohort (EC). We report here safety and efficacy for the whole cohort.

Results

38 patients (pts) were enrolled, 37 evaluable for safety and 36 for efficacy (12 included in DE). Median age 52 years (33-76). 44%were male. Median KPS 90%, Barthel 100%. 44% were MGMT methylated and 3 pts had IDH1/2 mutation. Most common related adverse events (AE) (all grades) included: nausea (67.6%), asthenia (62.2%), transaminase elevation (40.5%), neutropenia (32.4%) thrombocytopenia (29.7%), diarrhea (29.7%), anorexia (29.7%), vomiting (27%) and constipation (24.3%). In the EC 8/25 pts (32%) presented grade ≥3 AEs (transaminase elevation, thrombocytopenia). 97.2% finished concomitant therapy. 94.4% initiated adjuvant treatment, 67.7% completed 6 TMZ cycles. 18 pts (50%) started maintenance therapy. 8 pts are still on treatment. At the time of this analysis 24 pts have progressed and 1 died without progression. Median follow up was 13.7 months (m), median PFS was 10.78m (95% CI, 7.61-13.94), with 6 month PFS and 12 month PFS of 71.6% and 40.2% respectively. Median OS was 31.4 m(95% CI, 12.64-50.10) with 12month OS of 78.9% and 24month OS of 56.6%.

Conclusions

In this phase Ib study addition of crizotinib to standard RT and TMZ was safe and resulted in highly promising efficacy for newly diagnosed GB, deserving further investigation.

Clinical trial identification

NCT02270034.

Legal entity responsible for the study

GEINO.

Funding

PFIZER.

Disclosure

M. Martinez Garcia: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: ROCHE; Travel / Accommodation / Expenses: PFIZER. E. Pineda: Advisory / Consultancy: Celgene; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Amgen. All other authors have declared no conflicts of interest.

Background

Tepotinib is an oral, highly selective MET inhibitor being investigated in MET-driven solid tumors. Cancer patients often receive co-medications, many of which are subject to cytochrome P450 3A (CYP3A) or P-glycoprotein (P-gp)-dependent pharmacokinetics.

The potential of tepotinib to alter the exposure to such drugs was investigated in two clinical drug-drug interaction (DDI) trials.

Methods

The effect of multiple doses of the RP2D of tepotinib (500 mg QD) on the exposure of single doses of the sensitive CYP3A4 substrate midazolam and the sensitive P-gp substrate dabigatran etexilate were tested in healthy subjects, using randomized single-sequence two-period cross-over designs. The primary endpoints were C_max and AUC for the respective probe drugs; their corresponding ratios of the geometric least-squares means (GLSM) (90% CI) in the presence/absence of tepotinib were reported. Additional PK measures, safety and tolerability were also evaluated.

Results

Most participants were male (12/12 midazolam; 19/20 dabigatran etexilate); mean age 34 years (range 19–44). There was no increase in midazolam exposure with co-administration of tepotinib (Table), suggesting that no effect on the metabolism of CYP3A is to be expected. Co-administration of tepotinib led to a 39–45% increase in dabigatran etexilate exposure. No clinically relevant effects on laboratory values, vital signs or ECG parameters were observed or reported as an AE.Table:

480P

Conclusions

After multiple doses of tepotinib at the RP2D (500 mg QD), there was no relevant exposure increase of the sensitive CYP3A substrate midazolam, and a < 2-fold mean exposure increase of the sensitive P-gp substrate dabigatran etexilate, indicating that tepotinib is a weak P-gp inhibitor. Tepotinib was considered safe and well tolerated in these studies of healthy volunteers. In summary, the potential of tepotinib to cause clinically relevant DDI with CYP3A4- or P-gp-dependent drugs at the intended posology is considered low.

Clinical trial identification

NCT03492437 and NCT03628339.

Editorial acknowledgement

Medical writing assistance (funded by Merck KGaA, Darmstadt, Germany) was provided by Sandra Cuscó, PhD of Bioscript Group (Macclesfield, UK).

Legal entity responsible for the study

Merck Healthcare KGaA.

Funding

Merck Healthcare KGaA.

Disclosure

Ö. Yalkinoglu: Full / Part-time employment: Merck Healthcare KGaA. A. Becker: Full / Part-time employment: Merck Healthcare KGaA. A. Krebs-Brown: Full / Part-time employment: Merck Healthcare KGaA. R. Strotmann: Full / Part-time employment: Merck Healthcare KGaA. All other authors have declared no conflicts of interest.

Background

This is the first and only randomized trial testing the addition of an oncolytic virus to an immune checkpoint inhibitor in advanced melanoma. Previously, the study met its primary endpoint: the combo of T-VEC plus ipi resulted in a significantly higher objective response rate (ORR) vs. ipi alone (39% vs. 18%; odds ratio, 2.9; 95% Cl, 1.5–5.5; P = 0.002) (Chesney et al. J Clin Oncol. 2017). Here, we present results from the 3-year landmark analysis.

Methods

Pts with unresectable, stages IIIB to IV melanoma were randomized 1:1 to receive the combo or ipi alone. T-VEC was injected intratumorally on day 1 of wk 1 at 10⁶ plaque-forming units (PFU)/mL followed by subsequent doses at 10⁸ PFU/mL on day 1 of wk 4, and every 2 wks thereafter. Intravenous ipi (3 mg/kg) was given every 3 wks starting on day 1 of wk 6 for up to 4 doses. Response was assessed by investigators per immune-related response criteria every 12 wks until disease progression. The primary endpoint was ORR; key secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. This analysis occurred 36 months (mos) after the last pt was randomized.

Results

198 pts were randomized (98 to combo; 100 to ipi). As of 25 Feb 2019, the median follow-up time was 40.0 mos in the combo arm and 34.3 mos in the ipi arm. ORR was significantly higher with the combo vs. ipi alone (36.7% vs. 16.0%; odds ratio, 3.0; 95% CI, 1.6 to 6.0; P = 0.002). Median PFS was 13.5 mos with combo and 4.5 mos with ipi (hazard ratio, 0.78; 95% Cl, 0.55–1.11; P = 0.159). Median OS was not reached in either arm (HR, 0.85; 95% CI, 0.55–1.32; P = 0.480). 45 pts (45.9%) in the combo arm and 64 pts (64%) in the ipi arm received subsequent anticancer therapy, with the median time from randomization to the first subsequent therapy being 27.7 mos and 8.3 mos, respectively. No new safety signals were detected.

Conclusions

At the 3-year follow-up, T-VEC plus ipi combo continued to provide durable and statistically superior ORR compared with ipi alone. PFS was numerically longer with the combo than ipi. Survival is likely confounded by subsequent anticancer therapies (NCT01740297).

Clinical trial identification

NCT01740297, release date December 4, 2012.

Editorial acknowledgement

Medical writing assistance was provided by Yang Li (Amgen Inc).

Legal entity responsible for the study

Amgen.

Funding

Amgen.

Disclosure

J.A. Chesney: Advisory / Consultancy, Travel / Accommodation / Expenses: Replimune; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Merck; Research grant / Funding (institution): BMS; Licensing / Royalties, Patents, Royalties, and Other Intellectual Property: University of Louisville. I. Puzanov: Advisory / Consultancy: 4SC; Advisory / Consultancy: Amgen. F. Collichio: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck. P. Singh: Advisory / Consultancy: AstraZeneca. M. Milhem: Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Amgen; Advisory / Consultancy: Trieza; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Biontech. O. Hamid: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Merck; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Genentech; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sanofi/Regeneron; Research grant / Funding (institution): Arcus; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): CytomX; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Iovance; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): NextCure; Research grant / Funding (institution): Parker; Research grant / Funding (institution), Additional research funding for institution: Polynoma. : Pfizer. M.I. Ross: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution), Travel / Accommodation / Expenses: Provectus; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Castle Biosciences. P. Friedlander: Advisory / Consultancy: Regeneron; Advisory / Consultancy: Puma Biosciences; Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: Aspyrian Therapeutics; Shareholder / Stockholder / Stock options: Incyte; Shareholder / Stockholder / Stock options: Clovis; Shareholder / Stockholder / Stock options: Merrimack Phamaceuticals; Shareholder / Stockholder / Stock options: Allergan. C. Garbe: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Neracare; Honoraria (self), Advisory / Consultancy: Philogen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi. T. Logan: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Acceleron; Research grant / Funding (institution): Abbott; Research grant / Funding (institution): Abraxis; Research grant / Funding (institution): Argos; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Aveo; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Immatics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Synta; Research grant / Funding (institution): Threshold; Research grant / Funding (institution): Millenium; Honoraria (self), Research grant / Funding (institution), Additional research funding to institution disclosure: Tracon, Cerulean, EMD Serono, Macrogenic, Peloton, Iovance, MedImmune, Dynavax. : Prometheus. A. Hauschild: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD/Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pierre Fabre; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Provectus; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): Philogen; Advisory / Consultancy, Research grant / Funding (institution): Regeneron; Advisory / Consultancy: OncoSec. C. Lebbe: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self): Pierre-Fabre; Honoraria (self): Pfizer; Honoraria (self): Incyte; Officer / Board of Directors: Aventis. M. Yi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. A. Sharma: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. J.M. Mehnert: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: EMD Serono; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Amgen; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Polynoma; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Incyte. All other authors have declared no conflicts of interest.

Background

Hypoxia induced by antiangiogenic agents could cause a functional impairment of homologous recombination, thus sensitizing wild-type (wt) BRCA tumor cells to PARP inhibition. In a phase II study the combination of cediranib-olaparib increased progression free survival (PFS) in women with recurrent platinum sensitive OC with respect to olaparib.

Methods

123 patients were allocated in a 1:1:1 ratio to receive: 80 mg/m² weekly paclitaxel up to 24 weeks (control), olaparib 600 mg tablet (300 mg twice daily) together with 20 mg cediranib daily (continuous schedule) or 20 mg cediranib given 5 days/week (intermittent schedule) until progression. PFS comparison between experimental schedules and the control arm (alpha one-sided 5%; power 80% to detect a HR of 0.5) was the primary objective.

Results

Median platinum-free interval was 1.8 mos, 59% of patients were pretreated with >3 chemotherapy lines. Median PFS for paclitaxel, the continuous, and the intermittent schedules were 3.1, 5.7, and 3.8 mos. Estimated HR for PFS in continuous arm vs control was 0.76 (90% CI: 0.49-1.17), p = 0.28 by log-rank test. HR for PFS in intermittent arm vs. control was 1.08 (90% CI: 0.71-1.64), p = 0.76 by log-rank test. In the subgroup gBRCA wt (n = 109) the median PFS for paclitaxel, the continuous, and the intermittent schedules were 2.1, 5.8 and 3.8 mos and HR for PFS in continuous arm vs control was 0.63 (95% CI: 0.36 to 1.10; p = 0.10). The toxicity profile of the study arms was as expected and similar between experimental arms. 11%, 18%, and 7% in control, continuous and intermittent arm discontinued treatment for adverse events. Five serious adverse drug reactions occurred and two of these were fatal: one in the control and one in the continuous arm.

Conclusions

The combination of cediranib and olaparib is effective in heavily pretreated PROC patients with the advantage of an oral administration and good tolerability. The continuous schedule of cediranib-olaparib showed a promising trend towards improved PFS in comparison with weekly paclitaxel particularly in the BRCA wt population.

Clinical trial identification

IRFMN-OVA-7289, EudraCT: 2016-003964-38, NCT03314740.

Legal entity responsible for the study

Istituto di Ricerche Farmacologiche Mario Negri IRCCS.

Funding

AstraZeneca.

Disclosure

N. Colombo: Honoraria (self), Advisory / Consultancy: Roche/Genentech; Honoraria (self), Advisory / Consultancy: PharmaMar; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: BioCad; Advisory / Consultancy: Takeda. G. Tognon: Advisory / Consultancy: Amgen; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony: Tesaro. M. Ratti: Travel / Accommodation / Expenses: Tesaro Bio. All other authors have declared no conflicts of interest.

Background

The Nutritional Prognostic Index (INP) is a nutritional and immunological marker. The difference between concomitant pre and post chemoradiotherapy INP and its impact as a prognostic factor for recurrence in patients with locally advanced rectal adenocarcinoma remains unclear. With the aim of providing greater evidence of the recurrent prognostic role of the differential of the pre and post INP in patients with locally advanced rectal adenocarcinoma we carried out the present study.

Methods

Of the total of 206 patients, 74 patients were excluded. The analysis included 132 patients. INP formula: 10 * serum albumin (g / dL) + 0.005 * total lymphocyte count (per mm³). The INP values were determined in 2 points: before QT/RTneoadjuvant (preQT/RT INP ) and after the neoadjuvant QT/RT termination, (postQT/RT PNI). The difference in INP (dINP) was calculated with the formula: preQT/RT INP - postQT/RT INP.

Results

Table:

546P Univariate and multivariate analysis

In the Kaplan and meier analysis, recurrence free survival (SLR) was P = 0.03. Independent factors for recurrence were age and ECOG (95% CI 0.940 – 0.998¸ P = 0.037, HR 3.4 95% IC 1.26 – 9.6, P = 0.016). Our findings showed a better SLR in the low dINP subgroup, so we took it as a cutoff 5. Patients who presented a dINP less than 5, have a better SLR in relation to those who have a dINP > 5. P = 0.013.

Conclusions

The difference less than 5 between the nutritional index before and after neoadjuvant chemoradiotherapy in patients with locally advanced adenocarcinoma of the rectum is associated with an increase in SLR as an independent predictor of recurrence.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.