Cycles Of Chemo Research Articles

A phase 2/3 study of romiplostim N01 in chemotherapy-induced thrombocytopenia (CIT).

217 Background: CIT causes dose reduction or delay of chemotherapy (chemo), bleeding, and platelet (PLT) transfusion. This phase 2/3 study aimed to assess the efficacy and safety of romiplostim N01 in CIT. Methods: This trial comprising Part A (open-label) and B (randomized double-blinded) recruited patients (pts) with solid tumors or lymphoma and with CIT. In Part A, pts with a PLT count ≤200×10 9 /L before the day of chemo were included. Romiplostim N01 was injected subcutaneously per week (QW) for a 3-week chemo cycle at 1 μg/kg (group 1) or 2 μg/kg (group 2) for pts with a PLT count 100~200×10 9 /L, and at 2 μg/kg (group 3) for pts with a PLT count <100×10 9 /L. Primary endpoint was proportion of responders on the last day of chemo cycle, defined as pts who had an increase in PLT count of ≥30×10 9 /L from baseline for pts with a PLT count 100~200×10 9 /L, and an increase in PLT count of ≥30×10 9 /L or a PLT count ≥100×10 9 /L for pts with a PLT count <100×10 9 /L. In Part B, pts with a PLT count 75~150×10 9 /L were included and randomized 2:1 to receive romiplostim N01 or placebo QW at 2 μg/kg on day 1, and at 1 μg/kg on day 8 and 15 for two chemo cycles. Primary endpoint was proportion of responders, defined as pts resuming two consecutive chemo cycles without thrombocytopenia-induced dose modification (dose reduction by ≥15% or delay by ≥4 days or discontinuation) and without a rescue therapy. Results: In Part A, 50 pts were included between Mar 12, 2021 and Jul 29, 2021. The proportions of responders were 66.7% (10/15) in group 1, 53.3% (8/15) in group 2, and 90.0% (18/20) in group 3. Between Nov 8, 2022 and Jan 15, 2024, 63 pts were randomized in Part B. The proportion of responders in the romiplostim N01 group was significantly higher than that in placebo group (68.3% vs 40.9%). The adjusted rate difference was 27.6% (95% confidence interval [CI]: 2.1%, 50.2%). Treatment-related adverse events (TRAEs) occurred in 17 (41.5%) and 12 (54.5%) pts in the romiplostim N01 and placebo groups, of whom 1 (2.4%) and 0 were ≥grade 3. The most frequent TRAEs were nausea (12.2% vs 0), vomiting (12.2% vs 0), and increased aspartate aminotransferase (9.8% vs 4.5%). No treatment-related hemorrhage or death occurred. In pool analysis, the proportion of responders was 73.3% and 40.9% in pts treated with romiplostim N01 and placebo, respectively. The rate difference was 32.4% (95% CI: 9.2%, 52.9%). Conclusions: Romiplostim N01 showed promising efficacy and manageable safety in patients with CIT. Clinical trial information: PartA:NCT05851027 ; PartB:NCT05554913 . Pool analysis of Part A (pts with PLT count ≥75×10 9 /L) and Part B (all pts). Romiplostim N01 Placebo Rate Difference Part A+B (n=75) Part B (n=22) Romiplostim N01 (Part A+B) vs Placebo Lowest PLT count in Cycle 1, ×10 9 /L 85±41 59±32 / Highest PLT count in Cycle 1, ×10 9 /L 226±101 132±45 / Proportion of responders who completed the first chemo cycle without rescue therapy and without thrombocytopenia-induced dose modification of the second chemo cycle 55 (73.3%) 9 (40.9%) 32.4% 95% CI 61.9~82.9% 20.7~63.6% 9.2~52.9%

Role of Ginger in management of nausea among patients receiving chemotherapy.

Cancer patients treated with chemotherapy often face variety of side effects, with nausea and vomiting being the most frequent. Ginger (Zingiber officinale), contains natural compounds that can speed up the metabolism and increase intestinal motility. It is traditionally used to treat gastrointestinal disorders. The objective of this study was to evaluate the role of ginger in management of nausea among patients receiving chemotherapy. This crossover interventional study was conducted to evaluate the role of ginger in management of nausea among patients receiving chemotherapy. Study was carried out at chemotherapy daycare of Shifa International Hospital Islamabad, with a sample size of 90 patients, using non-probability convenient sampling. Patients undergoing chemotherapy were given the dose of ginger (550 mg twice a day) for five consecutive days. On the next chemo cycle the same patients were given the placebo capsules of same color and weight for two times a day for five days. Patients and attendants were contacted for five days and being asked about post-chemotherapy nausea. Nausea and vomiting were measured by Rhodes scale. Results showed that Rhodes score of patients taking Ginger capsules was significantly lower than those taking placebo (p-value < 0.05) in all the five days. Ginger significantly managed the nausea among patients receiving chemotherapy. Its natural antiemetic properties provide a convenient and safe way to reduce the post-chemotherapy nausea and vomiting.

Association of human interpretable features derived from pancreatic ductal adenocarcinoma pathology slides with disease-free survival.

e16368 Background: Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second cause of cancer death in the US by 2040. For the minority of patients who are candidates for curative-intent surgical resection, a neoadjuvant approach with chemotherapy or chemotherapy followed by chemoradiotherapy (chemoRT) has become the standard of care. The tumor microenvironment (TME) has been recognized as a key factor in therapeutic resistance and disease progression. This study aims to explore the prognostic value of human-interpretable machine learning image features (HIFs) derived from whole-slide H&amp;E images. Methods: Consecutive PDAC patients who underwent neoadjuvant therapy followed by surgical resection were studied in this single-institution retrospective study. Clinical variables collected include tumor site (head/body/tail), surgery extent, histology, sex, age at diagnosis, grade, treatment response (4-point scale), LVI, PNI, resection margin status, pathological TNM staging, number of lymph nodes removed/positive, neoadjuvant strategy (chemotherapy vs chemoRT), and number of neoadjuvant chemo cycles. These factors were analyzed with a multivariable Cox proportional hazards model for disease-free survival (DFS) after surgery. Additionally, 420 human-interpretable image features (HIFs) derived from a commercial machine learning software were analyzed with a univariable Cox model on a binary outcome of 1-yr DFS, applying a Bonferroni correction for multiple comparisons to identify significant predictors. Results: Increased neoadjuvant chemotherapy cycles (HR = 0.62, p = 0.001, [median: 8, IQR: 6-12]) and receipt of combination neoadjuvant therapy (HR = 0.15, p = 0.020, [29% chemo, 71% +chemoRT]) exhibited a protective effect in the multivariable DFS model. 3 HIFs quantifying immune cells and macrophages within the cancerous tissue and its stroma were associated with an improved probability of 1-year DFS. Conclusions: In addition to clinical factors, HIFs may offer valuable insights into the tumor microenvironment's influence on PDAC progression, paving the way for improved prognostic models and therapeutic strategies. Future work will integrate clinical predictors with HIFs in a combined model.

Functional hemodynamic imaging markers for the prediction of pathological outcomes in breast cancer patients treated with neoadjuvant chemotherapy.

Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a significant predictor of increased likelihood of survival in breast cancer patients. Early prediction of pCR is of high clinical value as it could allow personalized adjustment of treatment regimens in non-responding patients for improved outcomes. We aim to assess the association between hemoglobin-based functional imaging biomarkers derived from diffuse optical tomography (DOT) and the pathological outcome represented by pCR at different timepoints along the course of NACT. Twenty-two breast cancer patients undergoing NACT were enrolled in a multimodal DOT and X-ray digital breast tomosynthesis (DBT) imaging study in which their breasts were imaged at different compression levels. Logistic regressions were used to study the associations between DOT-derived imaging markers evaluated after the first and second cycles of chemotherapy, respectively, with pCR status determined after the conclusion of NACT at the time of surgery. Receiver operating characteristic curve analysis was also used to explore the predictive performance of selected DOT-derived markers. Normalized tumor HbT under half compression was significantly lower in the pCR group compared to the non-pCR group after two chemotherapy cycles (). In addition, the change in normalized tumor upon reducing compression from full to half mammographic force was identified as another potential indicator of pCR at an earlier time point, i.e., after the first chemo cycle (). Exploratory predictive assessments showed that AUCs using DOT-derived functional imaging markers as predictors reach as high as 0.75 and 0.71, respectively, after the first and second chemo cycle, compared to AUCs of 0.50 and 0.53 using changes in tumor size measured on DBT and MRI. These findings suggest that breast DOT could be used to assist response assessment in women undergoing NACT, a critical but unmet clinical need, and potentially enable personalized adjustments of treatment regimens.

Posaconazole versus voriconazole as antifungal prophylaxis for invasive fungal diseases in patients with hematological malignancies.

The incidence of invasive fungal diseases (IFDs) has risen in hematologic malignancy patients due to neutropenia. While posaconazole is recommended as the first-line antifungal prophylaxis in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients and voriconazole is an alternative, there is currently no direct comparison data available to assess their relative effectiveness. We retrospectively reviewed eligible patient charts from January 2017 to February 2019 to identify breakthrough IFD rates, drug adverse event frequency, and drug acquisition cost in AML/MDS patients. Forty-eight patients received 130 chemo cycles, with 50 (38%) cycles prescribed posaconazole and 80 (62%) prescribed voriconazole as primary IFD prophylaxis. The incidence rates of IFD in the posaconazole group were 8% (4 out of 50), of which two were probable and two were possible infections, while 6.26% (5 out of 80) of patients in the voriconazole group developed IFD, with four possible infections and one probable infection (p = 0.73). A higher percentage of patients in the voriconazole group discontinued prophylaxis due to adverse events, with six patients compared to two patients in the posaconazole group (p = 0.15). The drug acquisition cost of posaconazole is 5.62 times more expensive than voriconazole. The use of voriconazole instead of posaconazole for 130 chemo cycles would save $166,584.6. Posaconazole and voriconazole have comparable efficacy and safety in preventing IFD in AML and MDS patients receiving chemotherapy. However, posaconazole is more costly than voriconazole.

Case Report: The role of Panchagavya and Panchakarma treatment in the management of radiotherapy and chemotherapy side effects in infiltrative ductal carcinoma

The incidence rate of infiltrative ductal carcinoma of the breast is increasing worldwide. Chemo- and radiotherapy are commonly used after the surgical intervention for radical cure. The occurrence of various side-effects of these chemo-radiation therapies creates much discomfort to the patient. Therefore, the compliance rate of the patient towards their adoption becomes poor, or the patient is highly affected by their associated side effects in unavoidable circumstances. It is imperative to study the effect of safe, alternative options such as Panchakarma and Panchagavya treatment, which are widely used in clinical practice as an adjuvant therapy in various types of carcinoma. This report presents the case of a 31-year-old female patient diagnosed with right infiltrative ductal carcinoma of the breast, and who was advised to undergo chemo-radiation therapy after surgical intervention. However, as soon as she finished the first chemo cycle, she suffered from palpitations, loss of appetite, nausea, vomiting, severe restlessness, and hot flushes. She was rushed to the Kamdhenu Panchgavya Ayurvedic Clinic of Govigyan Anusandhan Kendra. Specific Panchagvya treatment, along with Mrudu Shodhana based on Ayurvedic principles, was prescribed to her (Kamdhenu Gomutra Ark, Laghusutshekhar Ras, Panchagavya Ghrita, Panchatikta Kshir Vasti, Anuvasana Vasti with Panchgavya Ghrita) throughout her total rounds of chemo- and radiotherapy. After starting the above-said Ayurvedic treatment, the patient experienced significant relief in all symptoms. Her full six sittings of chemo- and radiotherapy were smoothly completed without causing any untoward effect. The selected combination of Ayurveda medicines gave relief in all symptoms induced by chemo- and radiotherapy therapy due to their Vatanulomak, Pittghna, Dahahara, Balya and Rasayana properties. The present case study shows that the Panchakarma and Panchagavya treatments are effective in subside the side effects induced by chemo- and radiotherapy and improving the compliance rate of the patients towards these conventional therapies.

Abstract CT239: IMpower010: Updated overall survival and safety results from Asian patients in a Phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA NSCLC

Abstract Background The Phase III IMpower010 study (NCT02486718) met its primary endpoint at the disease-free survival (DFS) interim analysis (IA; clinical cutoff: Jan 21, 2021), demonstrating significant DFS improvement with atezolizumab (atezo) vs best supportive care (BSC) after adjuvant chemotherapy (chemo) in patients with resected stage II-IIIA NSCLC, including those with PD-L1 TC ≥1%. Based on these findings, atezo was approved as adjuvant therapy after platinum-based chemo in patients with completely resected PD-L1 TC ≥1% stage II-IIIA NSCLC in the US, China and other countries, and in patients with completely resected PD-L1 TC ≥50% stage II-IIIA NSCLC in the EU and other countries. In a previous exploratory analysis at the time of the DFS IA, the IMpower010 Asian subpopulation showed efficacy and safety outcomes that were consistent with those of the global population (Kenmotsu et al. JSMO 2021). Here we report updated data from the IMpower010 Asian subpopulation at the first overall survival (OS) IA. Methods The IMpower010 study design and DFS IA have been previously reported (Felip et al. Lancet 2021). Eligible patients with completely resected stage IB (≥4 cm)-IIIA NSCLC (AJCC/UICC v7) received one to four 21-day cycles of cisplatin-based doublet chemo and were subsequently randomized 1:1 to receive atezo 1200 mg q3w (16 cycles) or BSC. The first pre-specified OS IA was conducted at the clinical cutoff date of Apr 18, 2022. OS in the intention-to-treat (ITT) population will be formally tested if DFS in the ITT population reaches statistical significance at the final DFS analysis. Exploratory OS and updated safety outcomes were evaluated in the Asian subpopulation. Results The Asian ITT population included 233 patients recruited from Japan, mainland China, Taiwan, Korea and Hong Kong. At data cutoff (Apr 18, 2022), the unstratified OS HR was 0.73 (95% CI: 0.28, 1.88) in favor of atezo in the PD-L1 TC ≥1% (SP263) stage II-IIIA population (n=129). The Asian safety-evaluable population included 229 patients (atezo, n=122; BSC, n=107). Any-grade adverse events (AEs) were reported in 95.1% (atezo) and 72.0% (BSC) of safety-evaluable patients; events were Grade 3/4 in 24.6% and 13.1%, respectively. Grade 5 treatment-related AEs occurred in 1 patient in the atezo arm. AEs leading to atezo discontinuation occurred in 21.3% of patients treated with atezo. Conclusions The IMpower010 Asian subpopulation showed an OS trend favoring atezo vs BSC in the PD-L1 TC ≥1% stage II-IIIA population, as was observed in the global population, although OS data were not formally tested in either population at the first OS IA. With longer follow-up, the safety findings for atezo in the IMpower010 Asian subpopulation remained broadly unchanged, were consistent with those of the global IMpower010 population and were in line with the known safety profile of atezo. Medical writing support for this abstract was provided by Kia C. E. Walcott, PhD, of Nucleus Global, an Inizio Company, and funded by F. Hoffmann-La Roche, Ltd. Citation Format: Jie Wang, Yun Fan, Jian Fang, Jianxing He, Yunpeng Liu, Min Tao, Nasser Altorki, Enriqueta Felip, Heather Wakelee, Eric Vallieres, Rossella Belleli, Virginia McNally, Elizabeth Bennett, Barbara J. Gitlitz, Caicun Zhou. IMpower010: Updated overall survival and safety results from Asian patients in a Phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT239.

Concurrent chemoradiation with low-dose and long-duration weekly infusion of gemcitabine in unresectable squamous cell carcinoma of head and neck (SCCHN).

Concurrent chemoradiotherapy now represents the standard of care in locally advanced unresectable squamous cell carcinoma of the head and neck, and the administration of cisplatin in triweekly or weekly schedules is the most commonly used chemotherapeutic agent. However, the chemotherapeutic agent and its scheduling with radiation is still an area of investigation with safer toxicity profile and better response rates. Gemcitabine is a potent radiosensitizer, and non-cytotoxic concentration results in decreased systemic toxicity while maintaining radiosensitization properties. Furthermore, data are emerging for low-dose and long-duration infusion where this strategy is found to be effective and a safe alternative to standard brief infusion. Based on these two strategies, that is, non-cytotoxic concentration with long duration, we have explored the unique possibility of further lowering the toxicity profile without compromising the efficacy. Eligible patients of locally advanced unresectable squamous cell carcinoma of the head and neck underwent radiation treatment with concurrent gemcitabine. A total dose of 70 Gy in 35 fractions over a period of seven weeks with conventional fractionation schedule was delivered with cord off after 44 Gy. Concurrent gemcitabine was administered intravenously for over two hours once a week, 1-2 h before radiation and for seven consecutive weeks at 50 mg/m2. Fifty-two patients was enrolled in this study, out of which 41 completed the treatment. Fifty-nine percent completed treatment within seven weeks. Sixty-four percent were found to have received more than five cycles. Mean follow-up of patients was found to be 4.9 months. Sixty-eight percent had complete response. Stage III patients achieved more complete response compared to stage IV. There was no site-wise difference in achieving complete response. Patients who have received less than five chemo cycles or completed the treatment in more than seven weeks had less complete response. Sixty-one percent had severe mucositis while 39% developed mild/moderate mucositis. Considering skin toxicity, 80% were found to have mild/moderate skin toxicity, while only 20% suffered from severe grades of skin toxicity. Gemcitabine in low-dose and long-duration infusion is a potent radiosensitizer with safer hematological toxicity and manageable local toxicities.

Abstract B132: Addition of AMXT1501 (polyamine uptake inhibitor) plus DFMO (polyamine synthesis inhibitor) to standard-of-care chemotherapy/anti-GD2 antibody in the TH-MYCN mouse neuroblastoma model, enhances efficacy compared to addition of DFMO alone

Abstract Background: We used the TH-MYCN mouse model of neuroblastoma (NB) to determine the importance of simultaneously inhibiting both polyamine uptake and synthesis when added to standard-of-care chemotherapy/immunotherapy. Polyamines are essential cations frequently upregulated in tumors. We have shown the benefit of adding DFMO, an irreversible polyamine synthesis inhibitor, to standard-of-care chemotherapy in several NB mouse models (Evageliou, Clin Cancer Res 2016). Based on our work, a randomized Phase 2 COG trial of DFMO, added to chemotherapy/anti-GD2 immunotherapy, is ongoing for relapsed NB (NCT03794349). We recently showed in NB mouse models that DFMO efficacy is enhanced by adding the polyamine uptake inhibitor AMXT1501 (Gamble, Sci Transl Med, 2019). DFMO/AMXT1501 is now in adult clinical trial (NCT05500508). Preclinical modelling of polyamine-targeted therapeutics in TH-MYCN mice has been invaluable for supporting clinical trial design but has yet to include anti-GD2 immunotherapy. Methods: TH-MYCN mice were used to optimize DFMO/AMXT1501 therapy combined with temozolomide/irinotecan (TEM/IRI) or cyclophosphamide/topotecan (CYCLO/TOPO), and anti-GD2 (14G2a) antibody. We studied escalating doses of DFMO and AMXT1501 (n=10/group), with or without TEM/IRI or CYCLO/TOPO. 14G2a regimen was titrated toward human-relevant pharmacokinetic exposures to establish suitable conditions for combination therapies. Results: In the absence of chemo-immunotherapy, highest-dose DFMO (1.5%) and AMXT1501 (2.5 mg/kg/d) had greatest efficacy without increased toxicity. Median mouse survival was 2-fold greater compared with lower dose DFMO/AMXT1501 combinations, suggesting that maximising DFMO dose is critical. Similar improved efficacy was observed in combination with TEM/IRI or CYCLO/TOPO. Combining 14G2a (100ug 2x/wk, 18 wks; McNerney, Oncoimmunology, 2022) with either CYCLO/TOPO (single 5-day chemo cycle) or DFMO/AMXT1501 (1.5%/2.5 mg/kg/d) increased survival compared with either treatment alone. Combining all 5 drugs resulted in 100% survival at 1 year, with minimal toxicity. However substantial dose reductions of 14G2a (&amp;lt;25µg, 2 doses) and TEM/IRI or CYCLO/TOPO (single 2-day chemo cycle) were needed to identify clinically relevant backbones which achieved human-relevant 14G2a pharmacokinetics. Addition of DFMO alone to the clinically relevant CYCLO/TOPO/14G2a backbone did not result in benefit compared to backbone alone. In contrast, addition of AMXT1501 plus DFMO to the backbone significantly extended survival (P&amp;lt; 0.001). Conclusions: We have increased the utility of the TH-MYCN mouse model for preclinical modelling of polyamine inhibition, and other investigational treatments, by pharmacokinetics-driven optimization of anti-GD2 therapy with standard-of-care chemotherapy backbones. This approach will improve optimisation for future NB clinical trials. Our data highlight the importance of adding AMXT1501 to DFMO for polyamine inhibition and support a planned international DFMO/AMXT1501/chemotherapy/anti-GD2 trial for refractory NB. Citation Format: Jayne Murray, Ruby Pandher, Lin Xiao, Klaartje Somers, Jennifer Brand, Erin Mosmann, Stephanie Alfred, Frances Kusuma, Adam Kearns, Julie R Park, Lynley V Marshall, Chiara Gorrini, Louis Chesler, Michael D Hogarty, Andrew D J Pearson, Mark Burns, Jamie I Fletcher, David Ziegler, Murray D Norris, Michelle Haber. Addition of AMXT1501 (polyamine uptake inhibitor) plus DFMO (polyamine synthesis inhibitor) to standard-of-care chemotherapy/anti-GD2 antibody in the TH-MYCN mouse neuroblastoma model, enhances efficacy compared to addition of DFMO alone [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B132.

Assessment of Outcomes of Consolidation Therapy By Number of Cycles of Blinatumomab Received in Newly Diagnosed Measurable Residual Disease Negative Patients with B-Lineage Acute Lymphoblastic Leukemia: In the ECOG-ACRIN E1910 Randomized Phase III National Clinical Trials Network Trial

Introduction: ECOG ACRIN E1910 is a randomized phase III trial that showed that adults with newly diagnosed BCR::ABL1 negative acute lymphoblastic leukemia (ALL) who become MRD negative (&amp;lt;0.01%) after induction chemo who receive blinatumomab with conventional chemotherapy (chemo) have improved survival compared with those who received chemo only (Litzow et al, Blood (2022) 140: Supplement 2, LBA-1). However, not all pts were able to receive all four planned cycles of blinatumomab in consolidation. In this report we assessed outcomes of pts in the blinatumomab arm of the trial who received all 4 cycles of blinatumomab compared to those who received 1-2 cycles. Methods: Patient between the ages of 30 and 70 with newly diagnosed BCR::ABL1 negative B-lineage ALL were enrolled and initially received 2.5 months of combination induction chemo utilizing a BFM-like regimen adapted from the E2993/UKALLXII clinical trial, with pegaspargase (after induction only for patients &amp;gt;=55 years of age) and addition of rituximab for CD20 positive patients. After remission induction (step 1) pts in morphologic complete remission (CR/CRi) received an intensification course of high dose methotrexate with pegaspargase for CNS prophylaxis (step 2). At the conclusion of step 2, remission and MRD status were determined centrally by 6-color flow cytometry with MRD negativity defined as &amp;lt;0.01%. In the primary analysis subset, MRD negative patients were randomized to receive an additional 4cycles of consolidation chemo or 2 cycles of blinatumomab at 28 mcg/day (flat dose) for 28 days each cycle followed by 3 cycles of consolidation chemo, another 4-week cycle of blinatumomab (3rd cycle of blinatumomab) followed by an additional cycle of chemo and then a 4th cycle of blinatumomab (step 3). Following completion of consolidation chemo +/- blinatumomab, pts were given 2.5 years of POMP maintenance therapy timed from the start of the intensification cycle (step 4). Estimates of OS were calculated using the Kaplan-Meier method. Comparison of OS between treatment arms were conducted using the stratified log-rank test and Cox proportional-hazards model with age, CD20 status, rituximab use, and whether pts intend to receive HSCT or not as stratification factors. As the number of cycles needed to optimize outcome has not been studied, an unplanned landmark analysis was used to compare OS of pts in the blinatumomab arm who received all 4 cycles o those who received 1-2 cycles. Time 0 was chosen as 9 months post step 3 randomization (the time that patients were supposed to complete 4 cycles of blina). Four pts who received blinatumomab but died within 9 months post step 3 randomization were therefore excluded from this analysis. Results: The study was activated on December 17, 2013 and closed to enrollment on October 15, 2019. 772 pts were screened for the trial and 488 were enrolled on step 1 induction therapy. The median age of the pts was 51 years (range 30-70). 224 MRD negative pts were randomized, 112 pts to each arm. In the blinatumomab arm 12 pts received 1 cycle (11%), 32 pts received 2 cycles (29%), 4 pts received 3 cycles (4%) and 63 pts received 4 cycles (57%). The OS of pts who received 1-2 cycles of blinatumomab was compared to control (Figure 1) The difference was not significant (hazard ratio 0.62, 95% CI 0.28 to 1.34, p=0.22). Fig 2 compares the survival of those who received 1-2 cycles to those who received 4 cycles ( (HR: 0.39, 95% CI 0.12 to 1.16, p=0.076). Conclusion: The addition of blinatumomab to consolidation chemotherapy resulted in a significantly better overall survival compared to chemotherapy alone in pts with newly diagnosed B-lineage ALL who were MRD negative after intensification. This represents a new standard of care for pts aged 30-70 years with BCR::ABL1 negative ALL. The optimal dose and number of cycles is however unknown. In this unplanned subgroup analysis we demonstrate that a survival benefit can only be confirmed in patients who receive the intended 4 cycles of blinatumomab during consolidation. Further studies will be needed to determine if fewer cycles can provide a similar benefit.

Case Report: The role of Panchagavya and Panchakarma treatment in the management of radiotherapy and chemotherapy side effects in infiltrative ductal carcinoma

The incidence rate of infiltrative ductal carcinoma of the breast is increasing worldwide. Chemo- and radiotherapy are commonly used after the surgical intervention for radical cure. The occurrence of various side-effects of these chemo-radiation therapies creates much discomfort to the patient. Therefore, the compliance rate of the patient towards their adoption becomes poor, or the patient is highly affected by their associated side effects in unavoidable circumstances. It is imperative to study the effect of safe, alternative options such as Panchakarma and Panchagavya treatment, which are widely used in clinical practice as an adjuvant therapy in various types of carcinoma. This report presents the case of a 31-year-old female patient diagnosed with right infiltrative ductal carcinoma of the breast, and who was advised to undergo chemo-radiation therapy after surgical intervention. However, as soon as she finished the first chemo cycle, she suffered from palpitations, loss of appetite, nausea, vomiting, severe restlessness, and hot flushes. She was rushed to the Kamdhenu Panchgavya Ayurvedic Clinic of Govigyan Anusandhan Kendra. Specific Panchagvya Chikitsa, along with Mrudu Shodhana based on Ayurvedic principles, was prescribed to her (Kamdhenu Gomutra Ark, Laghusutshekhar Ras, Panchagavya Ghrita, Panchatikta Kshir Vasti, Anuvasana Vasti with Panchgavya Ghrita) throughout her total rounds of chemo- and radiotherapy. After starting the above-said Ayurvedic treatment, the patient experienced significant relief in all symptoms. Her full six sittings of chemo- and radiotherapy were smoothly completed without causing any untoward effect. The selected combination of Ayurveda medicines gave relief in all symptoms induced by chemo- and radiotherapy therapy due to their Vatanulomak, Pittghna, Dahahara, Balya and Rasayana properties. The present case study shows that the Panchakarma and Panchagavya treatment is effective to subside the side effects induced by chemo- and radiotherapy, and improve the compliance rate of the patients towards these conventional therapies.

Response-Adapted Omission of Radiotherapy in Pediatric Patients with Intermediate- and High-Risk Hodgkin Lymphoma Treated per EuroNet-PHL-C1: A Single Institution Analysis of Outcomes and Patterns of Failure

EuroNet-PHL-C1 demonstrated that 40% of intermediate- and high-risk pediatric Hodgkin lymphoma (HL) patients treated with OEPA-COPDAC chemotherapy achieved adequate response (AR) at early response assessment (ERA), and thus were able to omit radiotherapy (RT). However, patterns of failure with this treatment paradigm, and specifically, whether or not all initial sites of disease require RT for those with inadequate response (IR) at ERA is unknown. The purpose of our study is to examine outcomes and patterns of failure for those treated per EuroNet-PHL-C1 at our institution. Our hypothesis is that limiting RT to only sites of IR at ERA does not result in increased failures. An IRB-approved retrospective review of all intermediate- and high-risk classical HL pediatric patients treated at our institution per EuroNet-PHL-C1 between 2015 and 2021 was performed. Patients were treated per protocol with radiation omitted for those with AR (Deauville 1-2 and >75% tumor shrinkage) at ERA (PET/CDT after 2 cycles of chemo). For those with IR who required RT, only sites of IR (Deauville 3-5) at ERA were treated using involved site radiation treatment (ISRT), instead of all initial sites of disease as on EuroNet-PHL-C1. Outcomes including overall survival (OS) and progression free survival (PFS) were calculated using Kaplan-Meier curves and patterns of failure were classified as either initial site only, new site only, or initial and new sites. A total of 35 patients were identified, of which 33 had evaluable follow up with median follow up of 33 months. The median age at diagnosis was 14 (range, 4-18) and 48% were female. Of the 33, 7 (21%) had IR at ERA and thus required RT, while 26 (79%) were spared RT. In the group who received RT, 4/7 (57%) had initial B-symptoms and 4/7 (57%) had initial bulky disease, compared to 9/26 (35%) and 20/26 (77%), respectively, in those who did not receive RT. For our entire cohort, 2-year PFS and OS were 91% and 100%, respectively. For those who had RT, 2-year PFS was 83% compared to 92% in those who did not need RT. There was a total of 3 relapses (9%) at last follow up with 1/7 (14%) in those who had RT vs. 2/26 (8%) in those without RT. For the patient who relapsed after RT, relapse occurred both at initial and new sites. For the 2 who relapsed who did not receive RT, 1 was both in initial and new sites, while the other was initial site only. At our institution, the majority of patients treated per EuroNet-PHL-C1 avoided RT with excellent outcomes. For those requiring RT, limiting RT to only sites of IR at ERA does not appear to adversely affect outcomes, though analysis is limited by the low number of failures.

Overall survival (OS) by response to first-line (1L) induction treatment with atezolizumab (atezo) + platinum/gemcitabine (plt/gem) vs placebo + plt/gem in patients (pts) with metastatic urothelial carcinoma (mUC): Updated data from the IMvigor130 OS final analysis.

4503 Background: For pts without disease progression during 1L plt-based chemotherapy (chemo), maintenance immunotherapy is a new mUC treatment option. IMvigor130 was a global, randomized Phase III study evaluating 1L atezo + plt/gem (Arm A) vs atezo monotherapy (Arm B) and placebo + plt/gem (Arm C) in patients with mUC (Galsky Lancet 2020). The final analysis showed that improved OS in Arm A vs Arm C of the intention-to-treat (ITT) population did not reach statistical significance (Galsky ASCO GU 2023). Here we report a post hoc analysis examining OS outcomes by response during atezo/placebo + chemo “induction” based on the final OS analysis. Methods: For Arms A and C, per protocol, investigators pre-specified the type of chemo pts received (gem + either cisplatin [cis] or carboplatin [carbo]), which was also a randomization stratification factor. Pts without progressive disease (PD) were allowed to continue atezo or placebo after 4 to 6 cycles of plt/gem. This post hoc analysis evaluated post-induction (Wk 18) OS in pts who completed 4 to 6 cycles of chemo followed by ≥1 dose of atezo or placebo and who had a best response of at least stable disease (SD) without PD at any time (up to and including Wk 18 tumor assessment). Post-progression OS was evaluated in pts who had PD at any time (up to and including Wk 18 tumor assessment). OS analyses by type of chemo were also performed. Multivariable Cox proportional hazards models were used, with HRs adjusted for known prognostic factors (and response for non-PD pts) and stratified by enrollment stage. Results: The time from last pt randomized to the data cutoff (Aug 31, 2022) was 49 mo (overall ITT population). OS improvements favoring Arm A vs C appeared greater for pts treated with cis than with carbo. In the cis subgroup, OS rates at 36 mo were 47% (Arm A) and 34% (Arm C) for pts who achieved at least SD during induction. Additional efficacy data are shown. Conclusions: In this post hoc analysis, the initial response to induction therapy did not seem to impact OS outcomes. Consistent with prior analyses, these data suggest that cis-treated pts may derive a greater benefit from the addition of atezo than carbo-treated pts. Clinical trial information: NCT02807636 . [Table: see text]

Pembrolizumab vs placebo for early-stage non‒small-cell lung cancer after resection and adjuvant therapy: Subgroup analysis of patients who received adjuvant chemotherapy in the phase 3 PEARLS/KEYNOTE-091 study.

8520 Background: In the randomized, triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372), at the second interim analysis, pembrolizumab (pembro) significantly prolonged DFS vs placebo (pbo) in the overall population of patients (pts) with completely resected stage IB–IIIA NSCLC per AJCC v7 who may or may not have received adjuvant chemotherapy (chemo; up to 4 cycles) as recommended per local guidelines (n = 1177; HR, 0.76 [95% CI, 0.63–0.91]; P = 0.0014). Here we present outcomes for those pts who received 1–4 cycles of prior adjuvant chemo, per protocol. Methods: Eligible adults had pathologically confirmed, completely resected stage IB (T ≥4 cm), II, or IIIA NSCLC (AJCC v7) of any PD-L1 expression, ECOG performance status of 0 or 1, and had not received neoadjuvant radiotherapy or chemo. Pts were randomized 1:1 to pembro 200 mg or pbo Q3W for 18 doses (~1 year); receipt of adjuvant chemo (yes vs no) was one of the stratification factors. Dual primary endpoints were DFS in the ITT and PD-L1 TPS ≥50% populations. No alpha was assigned to this subgroup analysis of pts who received adjuvant chemo for 1–4 cycles per local guidelines. Results: Of 1177 pts in the ITT population, 1010 (85.8%) received adjuvant chemo and were included in this analysis (pembro, n = 506; pbo, n = 504). Pts received a median of 17 and 18 study doses, respectively. As of data cutoff (Sep 20, 2021), 52.6% in the pembro arm vs 64.9% in the pbo arm had completed treatment. Median time from randomization to data cutoff was 37.4 mo. Median (95% CI) DFS was 58.7 mo (39.2 mo–not reached [NR]) in the pembro arm vs 34.9 mo (28.6 mo–NR) in the pbo arm (HR, 0.73 [95% CI, 0.60–0.89]). Estimated 18-mo DFS rates were 73.8% and 63.1%, respectively. In pts with PD-L1 TPS ≥50% (pembro, n = 143; pbo, n = 141), median DFS was NR in both treatment arms (HR, 0.80 [95% CI, 0.54–1.20]). Grade 3–5 adverse events (AEs) occurred in 170 pts (34.3%) in the pembro arm and 128 (25.7%) in the pbo arm (grade 5, 2.2% vs 1.0%). Immune-mediated AEs and infusion reactions occurred in 195 pts (39.3%) in the pembro arm and 69 (13.8%) in the pbo arm. Conclusions: Consistent with the ITT population, pembro substantially improved DFS vs pbo in the subgroup of pts with stage IB (T2a ≥4 cm), II, or IIIA NSCLC who received adjuvant platinum-based chemo following complete resection. Based on these results, pembro was approved for adjuvant treatment in this pt population by the US FDA. Clinical trial information: NCT02504372 .

Anxiety Levels of Breast Cancer Patients Undergoing Chemotherapy During the Covid-19 Pandemic

Introduction: Breast cancer is a moderately severe disease characterized by uncontrolled growth and the continuous spread of abnormal cells that can damage the surrounding tissues. Goal: Anxiety levels of breast cancer patients undergoing chemotherapy during the Covid-19 pandemic. Method: Qualitative research with a case study approach. Kuesinoer Hamilton Rating Scale for Anxiety (HRS-A) measuring slat. Result: Showed the subject that I had undergone chemotherapy with a score of 25 in the moderate anxiety category. In subject II, the score was: 39 in the severe anxiety category. In subject III, the score resulted: 42 with a category of severe anxiety once. Conclusion: The anxiety level of breast cancer patients while undergoing chemotherapy varies with experienced and inexperienced chemo cycles during the Covid-19 period. Hospitals are expected to continue improving professional services, especially for breast cancer patients undergoing chemotherapy, which can assess the anxiety of breast cancer patients undergoing chemotherapy.

A case of missed mixed germ cell tumor of ovary in pregnancy

Ovarian germ cell tumor accounts for 18-26% of all ovarian cancers complicating pregnancy. This is a rare case of mixed germ cell tumor of ovary, misdiagnosed antenatally as uterine fibroid. A 34-year-old primigravida at 37 weeks + 5 days POG came in latent labor. Term scan showed fibroid of 11x 9cms in posterior wall in lower uterine segment with central cystic area. She underwent emergency LSCS and delivered a male baby weighing 2.005 kg. On exteriorization of uterus, a 10 x 8 cm necrotic mass was present posterior to uterus in rectovaginal space measuring 10 x 8 cm. It was concluded as FIGO Stage IC1 ovarian carcinoma.Histopathology of the mass showed mixed germ cell tumor: 60% yolk sac tumor and 40% dysgerminoma. MRI done after 2 weeks showed a lesion of 10.4 x 9.5 x 7.3 cm in rectovaginal pouch compressing and displacing the rectum posteriorly and to the left side, also displacing uterus and bladder anteriorly, Left ovary normal, Right ovary not visualized. Hence, she received 4 cycles of chemo comprising cisplatin and etoposide.After chemo, PET scan showed a lesion of 6.7x 6.2 x 4.2 cm in the rectovaginal area just right to the midline with right ovary not being visualized separately. Hence, she underwent laparoscopic right oophorectomy. Histopathology showed extensive regressive changes with occasional scattered atypical cells with no conclusive evidence of residual tumor. Follow up serum LDH and AFP are within normal limits and advised to follow up once in 3 months to look for any recurrences. : Any mass during pregnancy even if found to be benign, should be further evaluated and monitored regularly to reduce the morbidity /mortality to the mother.

Replacement of Antiretroviral Therapy with HIV Broadly Neutralizing Antibodies to Maximize the Effectiveness of Chemotherapy in HIV Patients with Lung Cancer.

Non-small cell lung cancer (NSCLC) is the most fatal non-AIDS defining cancer in people living with HIV (PWH) on antiretroviral therapy (ART). Treatment of malignancies in PWH requires concomitant cancer therapy and ART, which can lead to potential drug-drug interactions (DDIs) and overlapping toxicities. In this study, we hypothesize that replacement of ART with HIV broadly neutralizing antibodies (bNAbs) during cancer chemotherapy (chemo) may maintain HIV suppression and tumor inhibition while minimizing DDIs and overlapping toxicities. We compared HIV suppression, tumor inhibition, and toxicity between conventional treatment (ART plus chemo) and a new modality (bNAbs plus chemo) in humanized mice. Humanized mice infected with HIVYU2 and xenografted with human NSCLC A549 cells were treated with NSCLC chemo (cisplatin and gemcitabine) and first-line ART (dolutegravir, tenofovir disoproxil difumarate, and emtricitabine) or bNAbs (N49P9.6-FR and PGT 121) at human equivalent drug doses. We monitored plasma HIV RNA, tumor volume, and toxicities over five cycles of chemo. We found that chemo plus ART or bNAbs were equally effective at maintaining suppression of HIV viremia and tumor growth. Comparative analysis showed that mice on ART and chemo had significant reductions in body weight and significant increases in plasma creatinine concentrations compared with mice on bNAbs and chemo, which suggests that a combination of bNAbs and chemo produces less renal toxicity than an ART and chemo combination. These data suggest that bNAb therapy during concomitant chemo may be an improved treatment option over ART for PWH and NSCLC, and possibly other cancers, because bNAbs maintain HIV suppression while minimizing DDIs and toxicities.

HCRN GU14-188: Phase Ib/II study of neoadjuvant pembrolizumab and chemotherapy for T2-4aN0M0 urothelial cancer.

448 Background: Immune checkpoint inhibition (ICI) is a standard of care therapy in metastatic urothelial carcinoma (mUC) but its role in the muscle-invasive setting remains unclear. Prior neoadjuvant ICI studies have demonstrated promising antitumor activity. We report results of a multi-institutional phase Ib/II two-stage study investigating chemo-immunotherapy in patients (pts) with cisplatin eligible or ineligible muscle-invasive UC (MIUC) (NCT02365766). Methods: Eligible pts were surgical candidates with clinical stage T2-4aN0M0 UC. Pts were enrolled on either the cisplatin eligible (CE) or cisplatin ineligible (CI) cohort. Both cohorts received 5 doses neoadjuvant pembrolizumab 200 mg every 3 weeks. CE chemo comprised four 21-day cycles of gemcitabine 1000 mg/m2 day (d) 1,8 and cisplatin 70 mg/m2 d 1 or 35 mg/m2 d 1,8. CI chemo comprised three 28-day cycles of gemcitabine 1000 mg/m2 d 1,8,15. Chemo-immunotherapy was followed by definitive surgery (radical cystectomy or nephroureterectomy). Primary endpoint was investigator assessed pathologic muscle-invasive response rate (PaIR, ≤ypT1N0) assessed at definitive surgery. Null hypothesis was PaIR rates of 23% (CE) and 18% (CI) for type I error rate 4% and power 86%. Secondary endpoints were rate of definitive surgery, ypT0 rate, 18 month (mo) relapse free survival (RFS), and 36 mo overall survival (OS). Results: 82 pts (42 CE, 40 CI) enrolled. 1 CI pt withdrew before cycle 1. 88.1% (CE) and 87.2% (CI) pts received definitive surgery, leaving 37 CE and 34 CI pts evaluable for the primary endpoint. 81% CE pts completed all 4 chemo cycles (median 4), and 92% CI pts completed all 3 chemo cycles (median 3). Median pembrolizumab treatments was 5 (range 1-6) in both cohorts. Median follow-up was 54.8 mos (CE) and 29.2 mos (CI). Median age was 64 (CE) and 73 (CI) and stage &gt; T2 at diagnosis was 42.9% (CE) and 60% (CI). PaIR rate for evaluable CE pts was 54% (95% CI 38-69) with 41% pts (95% CI 27-57) down staged to ypT0. 18 mo RFS was 82% (95% CI 66-91) and 36 mo OS was 78.9% (95% CI 65-90). PaIR rate for evaluable CI pts was 53% (95% CI 37-69) with 41% pts (95% CI 26-58) downstaged to ypT0. 18 mo RFS was 65.1% (95% CI 48-78) and 36 mo OS was 65.7% (95% CI 47-79). Most common ≥ grade 3 toxicities were anemia (28.3%), hypertension (28.3%), and neutropenia (22.2%), with cytopenias more common in CE than CI pts. One death from post-operative sepsis occurred in cohort CE. Immune related adverse events (irAEs) ≥ grade 3 include elevated liver enzymes (3.7%), rash (2.5%), pneumonitis (2.5%), and colitis (2.5%). Conclusions: Neoadjuvant chemo-immunotherapy demonstrated significant down staging in CE and CI MIUC pts prior to definitive surgery, meeting the primary endpoint. Survival correlated with pathologic response. Further phase III studies will be necessary to confirm the efficacy and safety of these regimens. Ongoing analysis of biomarkers of response is underway. Clinical trial information: NCT02365766 .

Trimodality therapy with carboplatin/paclitaxel (CP) or FOLFOX (FFX) for esophageal/esogastric junctional cancer (EC/EGJ): Expanded safety and efficacy data from PROTECT.

370 Background: When combined to preoperative radiation therapy (RT), CP and FFX regimen provide both high complete resection (R0) rate for EC/EGJ cancer (Adenis, ASCO 2022). However, it appeared that neoadjuvant chemoradiation (nCRT) with CP is associated with a severe postoperative morbidity rate higher than expected. We present here the expanded safety and efficacy analyses from the PROTECT trial. Methods: PROTECT is a randomized, phase 2 trial which included stage II/III and ECOG PS ≤2 EC or Siewert I-II EGJ cancers. Patients (pts) received FFX or CP with concurrent RT (41.4Gy, 1.8Gy, 23 fractions), followed by surgery 4-8 weeks after completion of nCRT (Messager, BMC Cancer 2016). Co-primary endpoints were proportion of R0 rate and proportion of Clavien-Dindo severe postoperative morbidity. Main secondary endpoints were nCRT and postoperative safety (NCI CTCAE v.4), DFS and OS. Results: 41/50 (82%) and 39/50 (78 %) pts received the planned chemo cycles and concurrent RT in FFX and CP arms, respectively. Grade (gr.) 3–4 AEs related to nCRT (FFX 14/50, 28%; CP 14/50, 28%) occurring in ≥5% of pts included lymphopenia (n=3, 6%; n=4, 8%), neutropenia (n=1, 2%; n=3, 6%), fatigue (n=2, 4%; n=0) and esophagitis-related to RT (n=1, 2%; n=1, 2%). No death was reported during nCRT. Surgery (FFX and CP; mini invasive: 15 and 15, hybrid: 22 and 21, open: 7 and 12) was performed in 44 and 48 pts, in FFX and CP groups, respectively. The main gr. III-V surgical complications (Clavien-Dindo scale) occurring in ≥5% of pts included esophageal fistula (n=2/43 evaluable pts, 6%; 8/48, 17%), conduit necrosis (n=2, 5%; n=1, 2%), ARDS (n=3, 7%; n=3, 6%), pleural effusion (n=3, 7%; n=4, 8%), and haemorrhage (n=0; n=3, 6%). There were no postoperative deaths. With a median follow-up of 54m, median DFS were 12.3m and 20m (HR=0.84; 95%CI: 0.52-1.35; p=0.48) and median OS were 31.7m and 45.8m (HR=0.79; 95%CI: 0.47-1.32; p=0.36) in FFX and CP arms, respectively. Prognostic factors significantly associated to DFS in univariate analysis were: R0 resection, TRG1-2 and ypT0N0 status. Conclusions: A higher than expected number of severe esophageal fistula was observed in the CP arm. We could not demonstrate a significant benefit of CP compared to FFX in terms of survival outcomes, but the study was not primarily designed to specifically address this issue. Clinical trial information: NCT02359968 .

Reliability of patient-reported toxicities during adjuvant chemotherapy

BackgroundPatient-reported outcomes (PROs) are validated tools to assess the impact of efficacy and toxicities of cancer treatments on patients’ health status. Because of the demonstrated little reliability of humans in reporting memories of painful experiences, this work explores the reliability of cancer patients in reporting chemotherapy-related toxicities. AimThis study aims to evaluate the concordance between toxicities experienced by the patients during chemotherapy and toxicities reported to the doctor at the end of the cycles. MethodsQuestionnaires concerning chemotherapy-related toxicities were administered on days 2, 5, 8, 11, 14, and 17 of each chemo cycle and at the end of the same cycle to patients undergoing adjuvant chemotherapy. The co-primary end-points were Lins's concordance correlation coefficient (CCC) and mean difference between real-time and retrospective toxicity assessments. ResultsIn total, 7182 toxicity assessments were collected from 1096 questionnaires. Concordance was observed between the retrospective evaluations and the toxicity assessments at early (day 2), peak (maximum toxicity), late (day 14 or 17), and mean real-time evaluations for each chemotherapy cycle (CCC for mean ranging from 0.52 to 0.77). No systematic discrepancy was found between real-time and retrospective evaluations, except for peak, which was systematically underestimated retrospectively. ConclusionsToxicities reported by the patients to the doctor at the end of each chemotherapy cycle reflect what they actually experienced without any substantial distortion. This result is very relevant both for the clinical implications in daily patients’ management and in the light of the current growing impact on digital monitoring of PROs.