Higher Pathological Response Research Articles

Descriptive review of current practices and prognostic factors in patients with ovarian cancer treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC): a multicentric, retrospective, cohort of 234 patients.

Ovarian cancer (OC) is the primary cause of mortality in women diagnosed with gynecological cancer. Our study assessed pressurized intraperitoneal aerosol chemotherapy (PIPAC) as treatment for peritoneal surface metastases (PSM) from recurrent or progressive OC and conducted survival analyses to identify prognostic factors. This retrospective cohort study, conducted across 18 international centers, analyzed the clinical practices of patients receiving palliative treatment for PSM from OC who underwent PIPAC. All patients were initially treated appropriately outside any clinical trial setting. Feasibility, safety, and morbidity were evaluated along with objective endpoints of oncological response. Multivariate analysis identified prognostic factors for OS and PFS. From 2015-2020, 234 consecutive patients were studied, from which 192 patients were included and stratified by platinum sensitivity for analysis. Patients with early recurrence, within one postoperative month, were excluded. Baseline characteristics were similar between the groups regarding platinum sensitivity (platinum sensitive (PS) and resistant (PR)), but chemotherapy frequency differed, as did PCI before PIPAC. Median PCI decreased in both groups after three cycles of PIPAC (PS 16 vs. 12, p < 0.001; PR 24 vs. 20, p = 0.009). Overall morbidity was 22%, with few severe complications (4-8%) or mortality (0-3%). Higher pathological response and longer OS (22 vs. 11m, p = 0.012) and PFS (12 vs. 7m, p = 0.033) were observed in the PS group. Multivariate analysis (OS/PFS) identified ascites (HR 4.02, p < 0.001/5.22, p < 0.001), positive cytology at first PIPAC (HR 3.91, p = 0.002/1.96, p = 0.035), and ≥ 3 PIPACs (HR 0.30, p = 0.002/0.48, p = 0.017) as independent prognostic factors of overall survival/progression-free survival. With low morbidity and mortality rates, PIPAC is a safe option for palliative treatment of advanced ovarian cancer. Promising results were observed after 3 PIPAC, which did improve the peritoneal burden. However, further research is needed to evaluate the potential role of PIPAC as an independent prognostic factor.

Immunotherapy for Colorectal Cancer with High Microsatellite Instability: The Ongoing Search for Biomarkers.

Microsatellite instability (MSI) is a biological condition associated with inflamed tumors, high tumor mutational burden (TMB), and responses to immune checkpoint inhibitors. In colorectal cancer (CRC), MSI tumors are found in 5% of patients in the metastatic setting and 15% in early-stage disease. Following the impressive clinical activity of immune checkpoint inhibitors in the metastatic setting, associated with deep and long-lasting responses, the development of immune checkpoint inhibitors has expanded to early-stage disease. Several phase II trials have demonstrated a high rate of pathological complete responses, with some patients even spared from surgery. However, in both settings, not all patients respond and some responses are short, emphasizing the importance of the ongoing search for accurate biomarkers. While various biomarkers of response have been evaluated in the context of MSI CRC, including B2M and JAK1/2 mutations, TMB, WNT pathway mutations, and Lynch syndrome, with mixed results, liver metastases have been associated with a lack of activity in such strategies. To improve patient selection and treatment outcomes, further research is required to identify additional biomarkers and refine existing ones. This will allow for the development of personalized treatment approaches and the integration of novel therapeutic strategies for MSI CRC patients with liver metastases.

Induction immunochemotherapy conversion rate and survival outcomes versus chemotherapy in initially unresectable esophageal squamous cell carcinoma.

e16077 Background: Currently, no comparative study has been reported to elucidate whether the addition of immunotherapy in the induction setting could improve treatment efficacy and prolong the overall survival of initially-unresectable locally advanced esophageal squamous cell carcinoma (iuESCC). This study aimed to compare surgical conversion rate and short-term overall survival in induction chemotherapy (iC) and induction immunochemotherapy (iIC) for patients with iuESCC. Methods: In this multicenter retrospective cohort study, patients with the guideline-defined unresectable disease were included at four high-volume institutions. The primary endpoints were conversion surgical rate and overall survival (OS). Pathological complete response (pCR) was defined as the disappearance of tumor cells in the primary lesion site. Multivariate cox regression analysis was used to identify the independent significant prognostic factors associated with OS. The stabilized inverse probability of treatment weighting (IPTW) was applied to confirm the survival comparison between iIC and iC cohorts. Results: A total of 309 patients (150 in iIC and 159 in iC cohort) were included. A significantly higher conversion surgical rate was observed in iIC cohort (iIC vs. iC: 127/150, 84.7% vs. 79/159, 49.7%, P &lt; 0.001). In terms of pathological response, the rates of pCR were 22.0% and 5.1% in the iIC and the iC cohort, respectively (P = 0.001). A significant difference in OS was observed between iIC (not reached) and iC cohorts (median [95% CI]: 36.3 [27.2 – 45.5] months). The stabilized IPTW yielded similar results. Regimen (iIC vs. iC, HR 0.215, 95% CI: 0.102 - 0.454, P &lt; 0.001) and operation (Yes vs. No, HR 0.262, 95% CI: 0.161 - 0.427, P &lt; 0.001) were the significant prognostic factors for OS. Further, subgroup analysis revealed that significantly higher OS was seen in iIC cohort than that in the iC cohort (P = 0.003) in patients who had non-pCR disease. Conclusions: Immunochemotherapy plus conversion surgery in the induction setting had higher pathological response rate and better OS in iuESCC patients. Moreover, this combined modality also contributed to improving OS in patients with residual tumor burden. This study provided evidence for future randomized control trial designs.

Revisiting the optimal neoadjuvant immunotherapy regimen in resectable stage III melanoma based on the interferon gamma signature: A pooled analysis.

9516 Background: Neoadjuvant anti-PD1 has been shown to be superior to adjuvant administration. Combination of neoadjuvant ipilimumab (IPI) + nivolumab (NIVO) induces even higher pathologic response rates (pRR) and event-free survival (EFS), but at the cost of higher toxicity. We previously showed that the interferon gamma (IFN-γ) signature is associated with a higher pRR after neoadjuvant IPI+NIVO. We hypothesized that IFN-γ high patients (pts) might benefit from less toxic anti-PD1 monotherapy (mono), while IFN-γ low pts might need an escalated regimen with IPI 3mg/kg + NIVO 1mg/kg. Methods: In this pooled analysis, pts with macroscopic nodal melanoma who received neoadjuvant NIVO 1mg/kg + IPI 3mg/kg (IPI3/NIVO1), IPI 1mg/kg + NIVO 3mg/kg (IPI1/NIVO3), sequential IPI 3mg/kg and NIVO 3mg/kg (IPI3&gt;NIVO3), or NIVO mono (240mg; IFN-γ high pts only) from the OpACIN-neo, PRADO and DONIMI trials, were analyzed according to their baseline IFN-γ signature. RNA gene expression from baseline tumor biopsies was analyzed using the Nanostring nCounter platform. The IFN-γ scores were calculated using an algorithm and cut-off previously developed at the NKI and prospectively tested in the DONIMI trial. Results: Baseline tumor material was available from 151 pts (Table). Median follow-up was 42 months for the entire cohort and 19 months for NIVO mono pts. Combined IPI+NIVO in IFN-γ high pts induced similar major pathologic response (MPR) rates compared to NIVO mono in IFN-γ high pts (71% vs 80%, p=0.715), and significantly higher MPR rates compared to IPI+NIVO in IFN-γ low pts (71% vs 45%, p=0.003). At 18-months, EFS rates were 87%, 100% and 73% respectively, and overall survival (OS) rates were 98%, 100% and 96%. Notably, IPI3/NIVO1 seemed to induce a higher MPR rate than IPI1/NIVO3 in IFN-γ low pts (64% vs 41%), which was not statistically significant due to small subgroups. At 36 months, EFS was 91% vs 62% and OS was 91% vs 82%. Conclusions: Neoadjuvant NIVO mono seems to have equal outcomes as IPI+NIVO in IFN-γ high pts. IFN-γ low pts may benefit from IPI+NIVO with higher doses of IPI. Incorporating baseline biomarkers like the IFN-γ signature algorithm in neoadjuvant treatment decisions will optimize the risk-benefit ratio for these pts. [Table: see text]

Large, multifocal or portal vein-invading hepatocellular carcinoma (HCC) downstaged by Y90 using personalized dosimetry: safety, pathological results and outcomes after surgery.

Transarterial radioembolization (TARE) has recently been recognized as a bridging/downstaging therapy to surgery for early hepatocellular carcinomas (HCCs) with high rates of complete pathological necrosis (CPN) on liver explants. In patients with portal vein tumoral thrombus (PVTT), multifocal or large tumors, TARE has mainly a palliative role and surgery remains controversial in this poor-prognosis population. Personalized dosimetry recently proved to outperform standard dosimetry used in prior negative Y90 randomized-controlled trials. In this retrospective study, we evaluated safety, radiological and pathological response and outcomes in HCC patients with PVTT, multifocal or large tumors, who underwent surgery after downstaging using TARE with Y90-loaded glass microspheres with personalized dosimetry. Between December 2015 and October 2021, 18 unresectable patients (14/18 with PVTT) had surgery (16 resections, 2 liver transplantations) 6.2 months (range, 2-14.6 months) after a single Y90 treatment. No 90-day mortality was reported. Objective modified response criteria in solid tumors (mRECIST) response were noted in all but one patient. Complete and extensive (50-99%) necrosis was observed in 36% and 45% of tumors, respectively. The post-treatment tumor-absorbed dose significantly differed depending on the extent of pathological necrosis (P=0.045). Median overall survival and progression-free survival (PFS) were respectively of 61.8 months [95% CI: 31.4 months-not reached (NR)] and 49.3 months (95% CI: 14 months-NR). PFS was longer in patients with complete imaging response [median NR (none recurred or died) vs. 21.5 months (95% CI: 10.1 months-NR), P<0.001] and in those with complete pathological response [median NR vs. 22.5 months (95% CI: 10.1 months-NR), P<0.001]. Y90 TARE using personalized dosimetry can provide high rates of imaging and pathological response in patients with PVTT, large or multifocal HCC. Subsequent surgery is safe and leads to outcomes far exceeding expectations in an otherwise poor prognosis population with no chance for cure. Clinical trial number: NCT05045573.

Immunotherapy for localized MSI-H colorectal cancer: Characterizing endoscopic and imaging response.

3610 Background: Early data suggests that immunotherapy (IO) for localized colorectal cancer (CRC) is associated with high rates of pathologic complete response (pCR) and durable remission. This study aims to characterize endoscopic, imaging, and pathological outcomes among patients who received IO for localized CRC. Methods: This was a single-institution retrospective analysis of patients with MSI-H CRC who received at least one cycle of anti-PD-1 therapy for localized (stage I-III) MSI-H CRC. Patient and tumor characteristics were obtained from the clinical record. Endoscopy reports were assessed using standardized criteria to determine response and imaging was assessed using RECIST v1.1 where applicable. Endoscopic complete response (endoCR) was characterized by flat, white scar and/or telangiectasia without residual ulcer or nodularity. Categorical variables were compared using Fisher’s exact test. Results: 37 patients who received a median of 8 cycles of pembrolizumab (n = 36) or nivolumab (n = 1) for localized CRC were identified, of which 16 (43%) had a rectal primary. 10 patients (27%) had mucinous features on pathology. The best endoscopic response was complete response (CR) in 13 of 30 (43%) patients, which was achieved after a median of 6 cycles. The rate of endoCR after ≤ 4 cycles of IO was similar to the rate of endoCR after &gt; 4 cycles (29% vs 50%, p = 0.284). The best imaging response was CR in 6 of 32 (19%) of patients. The rate of CR on imaging after ≤ 4 cycles and &gt; 4 cycles of IO was 6% and 36% respectively (p = 0.064). In cases where imaging and endoscopy were available (n = 24), discrepancy in best response was noted in 14 (58%) cases. The most common discrepancy was partial response on imaging when endoCR was noted (n = 6 cases). 16 patients proceeded to surgical resection (after a median of 8 cycles) of which 11 (69%) had pCR despite non-CR on either endoscopy (n = 7) or imaging (n = 9). The endoscopic reports indicating residual disease prior to surgery included findings such as ulceration, scarring, strictures, and an obstructing mass. Of 15 patients who did not proceed to surgery and had follow-up more than 6 months after completion of IO, 13 (87%) had no evidence of progression at a median follow-up of 19.3 months from IO start. Conclusions: Discrepancies between endoscopic, imaging, and pathological outcomes were frequent, indicating a need for improved clinical response criteria. Nevertheless, immunotherapy was associated with deep and durable responses in most patients with localized MSI-H CRC.

A pilot phase II trial of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin (NeoCPC) for locoregionally advanced, resectable squamous cell carcinoma of the head and neck.

6069 Background: For resectable squamous cell carcinoma of the head and neck (HNSCC), novel therapeutic approaches are still needed to improve outcomes. Neoadjuvant immunochemotherapy (NICT) is considered as a potentially effective strategy. We therefore conducted a pilot phase II trial to explore the efficacy and safety of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin (NeoCPC) in patients with locoregionally advanced, resectable HNSCC. Methods: In this open-label phase II trial, patients with untreated locoregionally advanced, resectable HNSCC (T2‒T4, N0‒N3b, M0; AJCC, 8th Edition) received NICT with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2) and cisplatin (60 mg/m2) on day 1 of each 21-day cycle for three cycles, followed by radiotherapy or surgery. The primary endpoint was objective response rate (ORR) per RECIST version 1.1. Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), safety, disease-free survival (DFS), and overall survival (OS). Genomic biomarkers (genetic mutations, tumour mutational burden [TMB] and immune microenvironment) in baseline tumor samples were explored. Results: Between April 2021 and January 2022, 48 patients were enrolled (median age, 59 years [range 27–73]; 42 men [87.5%]). After completion of neoadjuvant therapy, patients underwent surgery (27, 56.3%), chemoradiotherapy (15, 31.2%), radiotherapy (five, 10.4%) or continued immunochemotherapy as maintenance therapy (one, 2.1%). At a median follow-up time of 415 days, the ORR was 89.6% (43/45). Of the 27 patients who had surgery, 17 (63.0%) patients had an MPR, including 15 (55.6%) with a pCR. Patients with ORR were more likely to achieve pCR. One patient died of lung metastasis 6 months after completion of treatment. The 1-year OS and DFS rates were both 97.9%. Only 3 (6.3%) patients had grade 3 treatment-related adverse events (AEs): one with pneumonitis and two with neurotoxicity. No unexpected immune-related AEs were observed. For genetic analysis, the most frequently mutated genes were TP53 (77.1%), CDKN2A, FAT1, CCND1 and NOTCH1. The lower radiographic tumor regression percentage was observed in TP53-altered ( p= 0.01) and TERT-altered ( p= 0.002) patients, whereas higher percentage was observed in HPV-positive patients. The median TMB was 3.15 mutations/MB. No significant difference was observed in TMB between patients with ORR and non-ORR (stable disease). There was a significant correlation between density of M1-like macrophage cells, CD8+ T cells in tumor area and radiographic tumor regression percentage ( p= 0.009, p= 0.0005, respectively). Conclusions: NeoCPC showed promising efficacy with a high ORR and pathologic response rate for locoregionally advanced, resectable HNSCC, with an acceptable safety profile. Clinical trial information: NCT04826679 .

The impact of emotional distress on pathologic response and survival after neoadjuvant combination immune checkpoint blockade (ICB) in high-risk stage III melanoma.

9558 Background: Neoadjuvant ICB has been shown to induce high pathologic response rates in high-risk stage III melanoma, outperforming adjuvant ICB with respect to survival benefit. Biomarkers that have been shown to predict ICB efficacy, including the interferon-gamma (IFN-γ) signature and tumor mutational burden (TMB), do not completely explain why some patients (pts) fail to benefit from neoadjuvant ICB. Emerging evidence in preclinical and clinical studies suggests that emotional distress (ED) negatively affects tumor progression and anti-tumor immune responses, mediated by β-adrenergic and glucocorticoid signaling. Here, we investigate the association between ED prior to neoadjuvant ICB and pathologic response and survival in pts with stage III melanoma treated in the PRADO trial. Methods: PRADO tested neoadjuvant ipilimumab + nivolumab followed by a response-directed surgical and adjuvant treatment regimen in stage III melanoma pts. The European Organization for Research and Treatment of Cancer (EORTC) scale for emotional functioning was used to identify pts with ED, based on established clinically relevant thresholds. Association between ED and pathologic response or survival was assessed using multivariable logistic or Cox regression analysis. Potential effects of ED on the tumor and its microenvironment were examined in baseline tumor biopsies using RNA sequencing. Results: Pts who completed the baseline EORTC questionnaire were included and defined as pts with ED (n = 28) or without ED (n = 60). Baseline characteristics, IFN-γ signature expression and TMB were comparable. Pts with ED showed a trend towards achieving less major pathologic responses (MPR; ≤10% viable tumor) compared to pts without ED (46% vs 65%, p = 0.099). Multivariable analysis showed a significant association between ED and MPR (OR 0.20, p = 0.043) when adjusted for age, sex, IFN-γ signature (OR 9.36, p = 0.002) and TMB (OR 13.21, p = 0.003). Pts with ED also had a significantly lower relapse-free survival (RFS) compared to pts without ED (2-year RFS 74% vs 91%, p = 0.011), and ED at baseline remained associated with relapse in multivariable regression (HR 3.81, p = 0.034) when adjusting for IFN-γ signature (OR 0.34, p = 0.109) and TMB (OR 1.02, p = 0.972). Analyses investigating the relation between ED with β-adrenergic and glucocorticoid signaling and factors representing anti-tumor immune responses are ongoing and will be presented at ASCO. Conclusions: Emotional distress was identified as baseline marker associated with impaired clinical outcomes after neoadjuvant combination ICB in pts with high-risk stage III melanoma. This data warrants further investigation in independent cohorts and into the potential effect of pharmacological and psychosocial interventions, e.g. adrenergic receptor blockade, on the anti-tumor immune response and patient outcomes. Clinical trial information: NCT02977052 .

The impact of response-directed surgery and adjuvant therapy on long-term survival after neoadjuvant ipilimumab plus nivolumab in stage III melanoma: Three-year data of PRADO and OpACIN-neo.

101 Background: Neoadjuvant ipilimumab (IPI) + nivolumab (NIVO) has been shown to induce high pathologic response rates associated with an excellent relapse-free survival (RFS) in high-risk stage III melanoma. While OpACIN-neo tested different neoadjuvant IPI + NIVO regimens followed by therapeutic lymph node dissection (TLND) without adjuvant systemic therapy (ST), PRADO tested a personalized approach. In patients (pts) achieving a major pathologic response (MPR; ≤10% viable tumor), TLND and adjuvant ST were omitted, and pts with pathologic non-response (pNR; &gt;50% viable tumor) were treated with adjuvant ST (BRAFi/MEKi or anti-PD1) ± radiotherapy after TLND. Here, we address 1) whether omitting TLND in MPR pts had an adverse effect on long-term survival and 2) whether adding adjuvant ST in pNR pts had a favorable effect on survival. Methods: The 3-year (3y) RFS and distant metastasis-free survival (DMFS) of pts with MPR and pNR from PRADO and OpACIN-neo were analyzed, comparing MPR pts with TLND versus without TLND and pNR pts with adjuvant ST versus without adjuvant ST. Survival rates were calculated and compared with Kaplan-Meier and log-rank methods. Associations between baseline characteristics and RFS or DMFS were examined by Cox regression analysis. Results: Median follow-up was 37.9 months in PRADO (cutoff Jan 8, 2023) and 46.8 months in OpACIN-neo (cutoff Feb 14, 2022). For MPR pts, TLND omission did not affect survival, with a 3y RFS of 93% versus 96% (p=0.47) and 3y DMFS 98% versus 98% (p=0.92) for pts without TLND (n=59) versus with TLND (n=53), respectively. In pNR pts, an indication for a RFS and DMFS benefit was seen favoring pts with adjuvant ST (n=17: n=10 BRAFi/MEKi and n=7 anti-PD1) over pts without adjuvant ST (n=23), with 3y RFS rates being 64% versus 35% (p=0.10) and 3y DMFS rates 70% versus 52% (p=0.24). Baseline clinical characteristics did not differ between PRADO and OpACIN-neo pts or were not associated with RFS and DMFS. Conclusions: Omitting TLND in MPR pts after neoadjuvant IPI + NIVO seems not to affect RFS/DMFS. Given the high survival rates, adjuvant ST is unlikely to give further benefit in these pts. In pts with pNR, addition of adjuvant ST with ongoing anti-PD1 or switch to BRAFi/MEKi appears to improve RFS and DMFS. Clinical trial information: NCT02977052 . [Table: see text]

Neoadjuvant Immunotherapy Increases Event-Free Survival in Melanoma

Neoadjuvant Immunotherapy Increases Event-Free Survival in Melanoma

Advances of immunotherapy-related biomarker in esophageal carcinoma

Esophageal carcinoma is one of the most common malignant tumors in the world, with incidence and mortality rankings of 7th and 6th, respectively. In recent years, immunotherapy represented by immune checkpoint inhibitors of programmed death-1 and programmed death ligand 1 (PD-L1) has been introduced into clinical practice and has changed the treatment status of esophageal cancer. Although immunotherapy has provided long-term survival benefits for patients with advanced esophageal cancer and high pathological response rates in the neoadjuvant therapy, only a few of the patients have satisfactory therapeutic outcomes. Therefore, effective biomarkers for predicting immunotherapeutic effects are urgently needed to identify those patients who could benefit from immunotherapy. In this paper, we mainly discuss recent research advances of biomarkers related to the immunotherapy of esophageal cancer and the clinical application prospects of these biomarkers.

Nonoperative Management of dMMR/MSI-H Colorectal Cancer following Neoadjuvant Immunotherapy: A Narrative Review.

Immunotherapy with PD-1 blockade has achieved a great success in colorectal cancers (CRCs) with high microsatellite instability (MSI-H) and deficient mismatch repair (dMMR), and has become the first-line therapy in metastatic setting. Studies of neoadjuvant immunotherapy also report exciting results, showing high rates of clinical complete response (cCR) and pathological complete response. The high efficacy and long duration of response of immunotherapy has prompt attempts to adopt watch-and-wait strategy for patients achieving cCR following the treatment. Thankfully, the watch-and-wait approach has been proposed for nearly 20 years for patients undergoing chemoradiotherapy and has gained ground among patients as well as clinicians. In this narrative review, we combed through the available information on immunotherapy for CRC and on the watch-and-wait strategy in chemoradiotherapy, and looked forward to a future where neoadjuvant immunotherapy as a curative therapy would play a big part in the treatment of MSI-H/dMMR CRC.

IFN-γ signature enables selection of neoadjuvant treatment in patients with stage III melanoma.

Neoadjuvant ipilimumab + nivolumab has demonstrated high pathologic response rates in stage III melanoma. Patients with low intra-tumoral interferon-γ (IFN-γ) signatures are less likely to benefit. We show that domatinostat (a class I histone deacetylase inhibitor) addition to anti-PD-1 + anti-CTLA-4 increased the IFN-γ response and reduced tumor growth in our murine melanoma model, rationalizing evaluation in patients. To stratify patients into IFN-γ high and low cohorts, we developed a baseline IFN-γ signature expression algorithm, which was prospectively tested in the DONIMI trial. Patients with stage III melanoma and high intra-tumoral IFN-γ scores were randomized to neoadjuvant nivolumab or nivolumab + domatinostat, while patients with low IFN-γ scores received nivolumab + domatinostat or ipilimumab + nivolumab + domatinostat. Domatinostat addition to neoadjuvant nivolumab ± ipilimumab did not delay surgery but induced unexpected severe skin toxicity, hampering domatinostat dose escalation. At studied dose levels, domatinostat addition did not increase treatment efficacy. The baseline IFN-γ score adequately differentiated patients who were likely to benefit from nivolumab alone versus patients who require other therapies.

Treatment outcomes of neoadjuvant chemotherapy with dose-dense AC-T regimen for patients with stage II, III breast cancer

Objective: To evaluate the treatment outcomes of neoadjuvant chemotherapy with dose-dense AC-T (dd AC-T) regimen on stage II, III breast cancer (BC) patients, and to assess several clinical and subclinical factors associated with treatment response in these patients. Subject and method: This was a cross-sectional, prospective study with longitudinal follow-up, no control group. The study was conducted on 44 stage II, III BC patients receiving NAC with dd AC-T regimen at Department of General Oncology, Institute of Oncology, 108 Military Central Hospital from June 2018 to August 2022. Result: After receiving NAC, CEA, CA15-3 mean concentrations and tumor size decreased statistically (p&lt;0.05). Regarding clinical response according to RECIST ver 1.1 criteria, the overall response rate (ORR) was 97.7%, in which the complete response (CR) rate accounted for 36.4%. All patients underwent surgery after receiving NAC. The rate of pathological complete response (pCR) was 31.8%. Several factors associated with treatment response include: Tumor size, skin involvement status, TNM stage, histopathology grade (p&lt;0.05). Patients achieving clinical CR had a higher rate of pCR than the other group (p&lt;0.001). Conclusion: NAC with ddAC-T regimen in treatment for stage II, III BC patients resulted in high clinical and pathological response. As a result, this is a good NAC option for these patients. Several factors associated with response include: Tumor size, skin involvement status, TNM stage, histology grade. Patients achieving clinical CR had a higher rate of pCR than the other group.

Neoadjuvant Therapy in Melanoma: Where Are We Now?

This review summarizes the current state of neoadjuvant immunotherapy and targeted therapy for locoregionally advanced melanoma. Melanoma systemic therapy has witnessed major advances with the development of immune checkpoint inhibitors and molecularly targeted therapy that have been translated into the neoadjuvant setting in managing locoregionally advanced disease. PD1 blockade as monotherapy and combined with CTLA4 blockade or LAG3 inhibition has demonstrated major improvements in reducing the risk of relapse and death that were associated with high pathologic response rates. Similar results were reported with BRAF-MEK inhibition for BRAF mutant melanoma with high pathologic response rates that appear to be less durable compared to immunotherapy. More importantly, in a recent randomized trial, event-free survival was significantly improved with neoadjuvant pembrolizumab compared to standard surgery and adjuvant therapy. Neoadjuvant therapy has become the standard of care for locoregionally advanced melanoma. Ongoing studies will define the most optimal combination regimens.

Neoadjuvant immunotherapy in resectable non-small-cell lung cancer.

The advent of immune checkpoint inhibition has pushed the treatment paradigm for resectable non-small-cell lung cancer (NSCLC) toward neoadjuvant therapy. A growing number of promising trials have examined the utility of neoadjuvant immunotherapy, both alone and in combination with other modalities such as radiation therapy (RT) and chemotherapy. The phase II LCMC3 and NEOSTAR trials demonstrated a role for neoadjuvant immunotherapy in inducing meaningful pathologic responses, and another phase II trial established the feasibility of combining neoadjuvant durvalumab with RT. Significant interest in neoadjuvant chemoimmunotherapy resulted in the conduct of multiple successful phase II trials including the Columbia trial, NADIM, SAKK 16/14, and NADIM II. Across these trials, neoadjuvant chemoimmunotherapy led to high rates of pathologic response and improved surgical outcomes without compromising surgical timing or feasibility. CheckMate-816, which was a randomized phase III trial studying neoadjuvant nivolumab in addition to chemotherapy, definitively established a benefit for neoadjuvant chemoimmunotherapy compared to chemotherapy alone for resectable NSCLC. Despite the growing literature and success of these trials, several outstanding questions remain, including the relationship between pathologic response and patient survival, the role of biomarkers such as programmed death ligand 1 and circulating tumor DNA in determining patient selection and treatment course, and the utility of additional adjuvant therapies. Longer follow-up of CheckMate-816 and other ongoing phase III trials may help address these questions. Ultimately, the complexity of managing resectable NSCLC highlights the importance of a multidisciplinary approach to patient care.

Neoadjuvant ipilimumab plus nivolumab in locally advanced melanoma: A real-world single-centre retrospective study

BackgroundNeoadjuvant immune-checkpoint inhibition (neoICI) with ipilimumab and nivolumab has shown high pathologic response rates as well as a long-lasting relapse-free survival in stage III melanoma patients. However, safety and efficacy data from real-world patients is very limited. MethodsStage IIIB-IV (M1a) melanoma patients with macroscopic nodal metastases with or without synchronous non-nodal lesions received combined neoICI with ipilimumab 1 mg/kg and nivolumab 3 mg/kg. Radiological and pathological response as well as relapse-free survival (RFS), event-free survival (EFS), overall survival (OS), melanoma-specific survival (MSS), adverse events (AE) related to neoICI and subsequent therapies were analysed. ResultsBetween November 2018 and October 2021, 23 patients received a combined neoICI. A pathologic response was achieved in 65% (15/23) of the patients, with 43% (10/23) achieving a pathological complete response. At a median follow-up of 22.8 months, median RFS, EFS, OS and MSS have not been reached. At a 3-year landmark, the RFS, EFS, OS and MSS rates were 77.6% (95% CI 60.1–100), 61.8% (95% CI 43.8–87.1), 62.0% (95% CI 42.2–91.0) and 76.7% (95% CI 55.7–100), respectively. Regarding AE, 70% (16/23) had immune-related AE (irAEs) of any grade which were classified as severe (≥ grade 3) irAEs in 13% (3/23) of patients. ConclusionThe combined neoICI with ipilimumab 1 mg/kg and nivolumab 3 mg/kg showed high response rates as well as long lasting relapse-free survival. Besides a promising efficacy, neoICI was well tolerated in our real-world patient cohort with only few high-grade irAEs indicating feasibility of neoICI in a non-trial setting.

A Wow for Neoadjuvant ICI in dMMR Colon Cancer.

Data from the NICHE-2 study indicate that patients with operable mismatch repair-deficient colon cancer benefit considerably from neoadjuvant immune checkpoint inhibition. A brief period of treatment with nivolumab and ipilimumab induced high pathologic response rates, did not delay surgery, and checked disease recurrence for a median of 13.1 months so far.

The Predictive Importance of Body Mass Index on Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer

Purpose: The aim of the study was to investigate the effects of body mass index (BMI) on the response to neoadjuvant chemotherapy (NACT) in Turkish patients with local and locally advanced breast cancer. Methods: The pathological responses for the breast and axilla were assessed according to the Miller-Payne grading (MPG) system. Tumors were grouped into molecular phenotypes and classified as response rates according to the MPG system after the completion of NACT. A 90% or greater reduction in tumor cellularity was considered a good response to treatment. Additionally, patients were grouped according to BMI into <25 (group A) and ≥25 (group B). Results: In total, 647 Turkish women with breast cancer were included in the study. In the univariate analysis, age, menopause status, tumor diameter, stage, histological grade, Ki-67, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and BMI were assessed to determine which of these factors were associated with a ≥90% response rate. Stage, HER2 positivity, triple-negative breast cancer (TNBC; ER-negative, PR-negative, and HER2-negative breast cancer), grade, Ki-67 levels, and BMI were found to be the statistically significant factors for a ≥90% response rate. In the multivariate analysis, grade III disease, HER2 positivity, and TNBC were found to be the factors associated with a high pathological response. Meanwhile, hormone receptor (HR) positivity and a higher BMI were associated with a decreased pathological response in patients receiving NACT for breast cancer. Conclusion: Our results show that a high BMI and HR positivity are associated with a poor response to NACT in Turkish patients with breast cancer. The findings presented in this study may guide novel studies to examine the NACT response in obese patients with and without insulin resistance.

961P Prospective real-world data of immuno(chemo)therapy (IO) prior to resection, definitive chemo-radiotherapy (CRT), or palliative therapy in patients with non-small cell lung cancer (NSCLC) without a primary curative option

Recent trials of IO prior to resection in locally advanced resectable NSCLC report high rates of pathological response and promising survival. However, primarily irresectable patients were excluded. Moreover, there is no data on CRT after IO in patients who are primarily not amenable to CRT. We hypothesized that induction IO may enable NSCLC patients with a potentially curative stage including oligometastatic disease (II – IVB [M1b]), for whom primary curative treatment (resection or CRT) is not possible for anatomical or functional reasons, to receive curative treatment.