Mitchell, Jessica L.

192 Background: Rectal cancer treatment paradigm has been evolving over time. Historically, for locally advanced rectal cancer, standard therapy (ST) consisted of neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy. Recently, total neoadjuvant treatment (TNT) approach that delivers both neoadjuvant chemotherapy (CAPOX or FOLFOX) and chemoradiation (or radiation only) prior to surgery is increasingly being utilized. The prognostic and predictive values of mismatch repair deficient (dMMR) in rectal cancer is not well characterized. Most dMMR patients receive the same treatment as MMR proficient (pMMR) patients although there is limited data that dMMR rectal cancer patients may not have the same level of benefits from neoadjuvant treatment. This retrospective study aims to evaluate the clinicopathological/molecular characteristics, disease response, and clinical outcomes in dMMR localized rectal cancer patients. Methods: A retrospective analysis was conducted on consecutive adult patients with a diagnosis of dMMR rectal cancer who were treated at Mayo Clinic between January 2000 to September 2021. Patients who presented with concurrent primary non-colorectal malignancies were excluded. The distributions of demographics, clinicopathological features, biomarkers, and outcome data were collected. Survival was assessed using Kaplan-Meier curves and Cox models were stratified by treatment arms to determine significance of treatment strategies. Results: Forty-one patients were identified with a median age of 45.3 years. Thirty (73.2%) pts were male. The most common MMR were loss of MSH2 and MSH6 (12/42; 29.3%) followed by loss of MLH1 and PMS2 (10/42; 24.4%) and solitary loss of MSH2 (4/42; 9.8%). The treatment, pathological response, and clinical outcomes are listed in table. With a median follow up of 101 months, only 6 patients (14.3%) died and median overall survival was not reached. Conclusions: Our findings showed dMMR localized rectal cancer responded to both ST and TNT with good clinical outcomes.[Table: see text]

402 Background: Pancreas cancer is an aggressive malignancy with limited therapeutic options. Nanoliposomal irinotecan (Nal-IRI) is a preferred second-line treatment, and current guidelines recommend its use in the absence of prior irinotecan. This study aimed to assess whether patients who had received regular irinotecan derive benefit from Nal-IRI. Methods: Medical records of metastatic pancreas cancer patients who had received regular irinotecan and then Nal-IRI were reviewed. The following information was extracted from each medical record: patient demographics, confirmation of a diagnosis of exocrine pancreas cancer, initial cancer stage, dates of administration of the drugs of interest, adverse events that occurred with Nal-IRI treatment, reasons for stopping regular irinotecan, and reasons for starting and stopping Nal-IRI. The primary endpoint was overall survival after the initiation of Nal-IRI (an a priori threshold of > 4 months defined success). Survival data were censored based on date of last follow up. Direct quotes from the medical record were documented to provide insight on prescribing Nal-IRI when guidelines advised the contrary. Results: Sixty four patients met eligibility criteria with a median age of 65 years (range: 36, 80 years). Prior to Nal-IRI, 61 patients had received FOLFIRINOX, and 3 FOLFIRI. Of these, 32 patients manifested progressive disease on regular irinotecan-based therapy. Nal-IRI was prescribed with a fluoropyrimidine; only one patient received monotherapy. At time of analysis, 54 patients had died. Median overall survival from initiation of Nal-IRI was 5.1 months (95% confidence interval (CI): 5.6, 4.3, months). An exploratory comparison, based on no cancer progression with regular irinotecan versus progression, showed improved survival with Nal-IRI in the former group: 6.1 months (95% CI: 9.3, 5.1 months) versus 4.3 months (95% CI: 4.8, 2.3 months); p=0.0006. Nal-IRI adverse events occurred as expected. Qualitative data illustrated several themes, including “limited treatment options,” which appeared to drive the decision to prescribe Nal-IRI. Conclusions: Nal-IRI might be considered in pancreas cancer patients who had received regular irinotecan, particularly in the absence of disease progression with the latter.

4048 Background: PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine containing 12 immunogenic epitopes derived from 7 cancer testis antigens (CTAs) frequently expressed in patients with CRC. Here we report the final results of the phase I study of PolyPEPI1018 vaccine as an add-on to maintenance therapy in mCRC patients. Methods: 11 patients with MSS mCRC were vaccinated with PolyPEPI1018 just after the transition to maintenance therapy with fluoropyrimidine/bevacizumab after first-line combo chemotherapy and bevacizumab. Part A: n = 5, single dose; Part B: n = 6, 3 doses, Q12W. Primary endpoint was safety. Immunomonitoring was performed at both blood and tumor levels, as well as prospectively predicted. Results: The vaccine was well tolerated; most common side effects were transient skin reactions. No vaccine-related SAE occurred. Pre-existing immune responses were boosted by the vaccine for 7/10 patients. De novo responses were also induced, overall, 80% of patients had CD8+ T cell responses against at least 3 CTAs. The magnitude of immune responses as well as the density and the ratio of CD8+/CD3+ tumor infiltrating T cells increased with multiple vaccine doses. Three patients had objective tumor response according to RECIST v1.1: one of them in the single dose group and two of them in the 3 doses group. Both patients in the 3 doses group qualified for curative surgery. One of them had no viable tumor cells in his primary tumor at the time of surgery. Post-trial follow-up revealed PFS of at least 12 months for 3 patients. mPFS was longer for patients receiving multiple doses (9.9 months) compared to single dose (6.1 months). Both measured and predicted multiantigenic immune responses tend to correlate with PFS and tumor volume reduction. Conclusions: PolyPEPI1018 was effective in restoring immunological responses to CTAs in patients’ with spontaneous immunity against. Treatment with PolyPEPI1018 vaccine and maintenance therapy was safe and demonstrated evidence of early clinical activity in MSS mCRC tumors. Data support further randomized trials with PolyPEPI1018. Clinical trial information: NCT03391232 .

Objective: This study sought to understand the patients’ perspective of what contributes to an absence of discussions of sexual orientation (SO), gender identity (GI), and sexual health in cancer care. Methods: Patients were recruited from oncology, gynecology, and a gender transition clinic to participate in semistructured interviews, which were analyzed with qualitative methods. Results: A total of 25 patients were interviewed, shedding light on 2 themes. The first was that these conversations are important but infrequent. One patient explained, “…. we know people who have had sex changes…[they] would have appreciated that question.” In response to whether sexual health was ever brought up, one patient responded, “No doctor ever has.” Patients described unaddressed issues: “There have been times, you know, we’ve wondered if it was okay to make love.” The second theme consisted of 4 pragmatic, patient-provided points to facilitate discussions: (1) implementation of a scale of 1 to 10 (with 10 being comfortable) to first gauge patients’ comfort in talking about SO, GI, and sexual health; (2) having the health-care provider explore the topic again over-time; (3) making sure the health-care provider is comfortable, as such comfort appears to enhance the patient’s comfort (“I have a doctor here, a female doctor, who just matter of fact will ask if I get erections and so on because of the medication she’s giving me);” and (4) eliminating euphemisms (one patient stated, “I don’t know what you mean by ‘sexual health’.”). Conclusion: Oncology health-care providers have a unique opportunity and responsibility to address SO, GI, and sexual health.

Objective: A growing number of cancer antineoplastic agents can cause life-threatening acute infusion reactions. Because previous studies have not studied these reactions from the perspective of patients, this study was undertaken with that objective in mind. Methods: Patients who had an acute infusion reaction were interviewed based on the Leventhal model. Once saturation of content was achieved, interviews were transcribed and analyzed with qualitative methodology. Results: Twenty-one patients were enrolled. Most were women (n = 15); the median age was 58 years, and paclitaxel was the most common inciting agent. Three themes emerged. First, these reactions are frightening; patients made remarks such as “I was just thinking oh my God, I am dying.” Second, prior education about these reactions seemed to mitigate this fear, “Basically everything the nurses told me potentially could happen, like happened. So, I was prepared.” Third, when health-care providers were prompt and attentive during the reaction, patients described less fear with future chemotherapy, “So no, I’m really not fearful about going in tomorrow because I know they’ll be there and they’ll be watching me.” Conclusion: These reactions evoke fear which can be mitigated with education prior to and with prompt responsiveness during the acute infusion reaction.