Improvement In Complete Response Rate Research Articles

Olanzapine as Antiemetic Prophylaxis in Moderately Emetogenic Chemotherapy

The role of olanzapine has not been adequately evaluated in moderately emetogenic chemotherapy (MEC) regimens with or without neurokinin-1 receptor antagonists. To evaluate whether addition of olanzapine to an MEC regimen reduces nausea, vomiting, and use of nausea rescue medications among patients with solid malignant tumors. This multicenter, open-label phase 3 randomized clinical trial included patients aged 18 years or older with solid malignant tumors who were receiving oxaliplatin-, carboplatin-, or irinotecan-based chemotherapy. The trial was conducted at 3 institutes in India from March 26, 2019, to August 26, 2023; the final cutoff date for analysis was September 10, 2023. Patients were randomized 1:1 to dexamethasone, aprepitant, and palonosetron with olanzapine (experimental group) or without olanzapine (observation group). The experimental group received 10 mg of olanzapine orally once at night on days 1 through 3 of the chemotherapy regimen. The primary end point was complete response (CR), defined as the proportion of patients with no vomiting, no significant nausea (scored as <5 on a visual analog scale of 1 to 100), and no use of rescue medications for nausea. Secondary end points included the proportion of patients experiencing nausea and chemotherapy-induced nausea and vomiting (CINV), receiving rescue medications, and experiencing adverse events. A total of 560 patients (259 [64%] male; median age, 51 years [range, 19-80 years]) were randomized. The analysis included 544 patients with evaluable data (274 assigned to olanzapine and 270 to observation). Baseline characteristics were evenly matched between the 2 groups. The proportion of patients with CR was significantly greater in the group with (248 [91%]) than without (222 [82%]) olanzapine in the overall 120-hour treatment period (P = .005). Likewise, there were significant differences between the olanzapine and observation groups for nausea control (264 [96%] vs 234 [87%]; P < .001) and CINV (262 [96%] vs 245 [91%]; P = .02) during the overall assessment period, and the proportion of patients receiving rescue medications significantly increased in the observation group (30 [11%]) compared with the olanzapine group (11 [4%]) (P = .001). Grade 1 somnolence was reported by 27 patients (10%) following administration of chemotherapy and olanzapine and by no patients in the observation group. In this randomized clinical trial, the addition of olanzapine significantly improved CR rates as well as nausea and vomiting prevention rates in chemotherapy-naive patients who were receiving MEC regimens containing oxaliplatin, carboplatin, or irinotecan. These findings suggest that use of olanzapine should be considered as one of the standards of care in these chemotherapy regimens. Clinical Trials Registry-India (CTRI) Identifier: CTRI/2018/12/016643.

Tislelizumab versus placebo combined with induction chemotherapy followed by concurrent chemoradiotherapy and adjuvant tislelizumab or placebo for locoregionally advanced nasopharyngeal carcinoma: Interim analysis of a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial.

6001 Background: Patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) have a risk of disease relapse after induction chemotherapy (IC)-concurrent chemoradiotherapy (CCRT). Early phase trials indicated that tislelizumab (PD-1 inhibitor) plus IC followed by CCRT have the potential to deepen responses and extend survival in LANPC. Here, we report the interim results of a phase 3 trial to evaluate the efficacy and safety of tislelizumab plus IC, followed by CCRT and adjuvant tislelizumab therapy in LANPC. Methods: Patients with high-risk LANPC (stage III-IVa, AJCC 8th Staging System, excluding T3N0, and T3N1 with retropharyngeal lymph nodes +) were randomized (1:1) to receive 200 mg tislelizumab or placebo + gemcitabine and cisplatin (GP) every 3 weeks (Q3W) for 3 cycles, followed by CCRT and adjuvant tislelizumab or placebo Q3W for up to an additional 8 cycles. Stratification factors were center and disease stage (III or IVa). Dual primary endpoints were complete response rate (CRR) after induction therapy and progression-free survival (PFS) per RECIST 1.1 by investigator under blinded review. The planned interim analysis (IA) for evaluating the first primary endpoint, CRR, was scheduled at 4 weeks after the completion of induction therapy to test whether addition of tislelizumab to standard IC significantly improved CRR, with allocated alpha at 0.005. Results: Between June 2022, and May 2023, 450 patients were randomized to tislelizumab arm (n = 223) and placebo arm (n = 227). Baseline characteristics were balanced between the two arms. At IA, 93.7% and 93.8% of patients completed 3 cycles of induction therapy in tislelizumab arm and placebo arm, respectively. Significant improvement in CRR was observed in tislelizumab arm vs placebo arm in the intent-to-treat population (ITT) (30.5% vs 16.7%; P = 0.0006). Improvement in CRR in tislelizumab arm vs placebo arm was consistent across key subgroups including disease stage (III [33.8% vs 20.7%]; IVa [28.7% vs 14.5%]), sex (male [28.3 % vs 15.7%]; female [38.0% vs 19.7%]), and ECOG PS (PS of 0 [28.8% vs 16.2%]; PS of 1 [40.6% vs 19.4%]). The ORR was 93.3% in the tislelizumab arm and 90.7% in the placebo arm. In safety population (tislelizumab arm, n=219; placebo arm, n=224), the incidence of Grade ≥3 TEAEs (40.6% vs 39.3%) and SAEs (2.3% vs 1.3%) were similar between two arms. Conclusions: The trial met its first primary endpoint with a statistically significant improvement of CRR with the addition of tislelizumab to standard IC in high-risk LANPC. Induction therapy with tislelizumab plus GP was generally well tolerated with manageable safety profile. Continued follow-up is being conducted to assess long-term efficacy and safety. Clinical trial information: NCT05211232 .

Effect of Treatment of Residual Disease After Immunotherapy-Based Combinations on Complete Response Rate of Patients With Metastatic Renal Cell Carcinomas

IntroductionImmune checkpoint inhibitor (ICI)-based combinations have revolutionized the management of first-line metastatic renal cell carcinoma (mRCC) by improving patient survival. Large phase 3 randomized trials assessing ICI-based combinations have reported complete response (CR) rates of 10% to 18% in the first-line setting. However, there is a scarcity of data about the effect of treatment of residual disease regarding CR rates improvement. Materials and MethodsWe included retrospectively all consecutive mRCC patients treated in first-line setting at the Institut de Cancérologie Strasbourg Europe with an ICI-based combination involving ICI or TKI, either alone or with added local treatment of residual disease. Patients were characterized according to IMDC risk. Radiologic response was defined according to RECIST v1.1. ResultsWe enrolled 80 mRCC patients treated with ICI-based combinations between May 2015 and May 2022. The median age was 63 years. Regarding IMDC risk, there were 12 favourable (15%), 50 intermediate (63%), and 18 poor-risk (22%) patients. Forty-seven patients (59%) received ICI + ICI, 24 (30%) received ICI + TKI, and 9 (11%) received another ICI-based therapy. In total, 8 achieved CR (10%), 36 patients (45%) achieved partial response, 23 (29%) achieved stable disease and 12 achieved progressive disease (15%) as the best response with systemic therapy alone. By adding local treatment of residual disease, 11 additional patients (14%) achieved radiological NED. Residual disease resected sites included kidney (n = 6), lymph nodes (n = 5), lung metastases (n = 2) and liver metastases (n = 1). ConclusionsThe resection of residual disease after first-line ICI-based therapy is associated with improved CR rate (CR + NED) in patients with mRCC. These results need to be validated in prospective trial. Patient SummaryIn recent years, the advent of immunotherapy has radically changed the management of patients with metastatic kidney cancer. Approximately 10% to 18% of these patients using immune checkpoint inhibitor (ICI)-based combinations no longer have detectable disease on CT scans (complete response). There are currently few data on the use of treatment of residual disease to increase the number of patients in complete response. In this retrospective study, the complete response rate with ICI-based treatment was 10%. When local treatment was added, the number of patients with a complete response increased to 24%. This strategy could increase the number of patients with a prolonged complete response in the future.

Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial

Sabatolimab is an immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), an immuno-myeloid regulator expressed on immune cells and leukaemic stem cells. In this trial, we compared the efficacy and safety of sabatolimab plus hypomethylating agent with placebo plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes. STIMULUS-MDS1 was a multicentre, randomised, double-blind, placebo-controlled, phase 2 study done at 54 investigational sites in 17 countries. Adult patients (aged ≥18 years) with intermediate-risk, high-risk, and very high-risk myelodysplastic syndromes (according to Revised International Prognostic Scoring System criteria) who had not received previous treatment were included. Patients were randomly assigned (1:1) to intravenous sabatolimab (400 mg on day 8 and 22) or placebo plus a hypomethylating agent (intravenous decitabine 20 mg/m2 on day 1-5 or intravenous or subcutaneous azacitidine 75 mg/m2 on day 1-7 or day 1-5 and day 8 and 9) every 28 days until treatment discontinuation. The two primary endpoints were complete response rate and progression-free survival, assessed in the full analysis set, which included all randomly assigned patients. Complete response was analysed, as prespecified, 7 months after the last patient was randomly assigned. All other analyses presented, including progression-free survival, were done at the final data cutoff prespecified via a protocol amendment on Sept 2, 2021. Safety was assessed in in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03946670, and is ongoing. Between July 29, 2019, and Aug 10, 2020, 127 patients were randomly assigned to sabatolimab plus a hypomethylating agent group (sabatolimab group; n=65) or placebo plus a hypomethylating agent (placebo group; n=62). The median age of participants was 73 years (IQR 69-77), of whom 86 (68%) of 127 patients were male and 77 (61%) were White. The primary endpoints were not met. Complete response (cutoff date of March 10, 2021) was achieved in 14 (22%; 95% CI 12·3-33·5) of 65 patients in the sabatolimab group vs 11 (18%; 9·2-29·5) of 62 patients in the placebo group (p=0·77). At the cutoff date of the final analysis (March 1, 2022), median follow-up for progression-free survival was 17·8 months (IQR 16·6-19·4) in the sabatolimab group and 19·2 months (17·7-22·3) in the placebo group, and the median progression-free survival was 11·1 months (95% CI 7·6-17·6) in the sabatolimab group vs 8·5 months (6·9-11·3) in the placebo group (hazard ratio 0·75 [95% CI 0·48-1·17]; p=0·1022). The most common adverse events of any grade were neutropenia (35 [56%] of 62 patients in the sabatolimab group vs 43 [68%] of 63 patients in the placebo group), thrombocytopenia (30 [48%] vs 32 [51%]), constipation (29 [47%] vs 24 [38%]), diarrhoea (27 [44%] vs 14 [22%]), anaemia (22 [35%] vs 34 [54%]), febrile neutropenia (22 [35%] vs 15 [24%]), and leukopenia (15 [24%] vs 20 [32%]). One patient developed a serious potential treatment-related immune-mediated adverse event in the sabatolimab group. There was one treatment-related death in the sabatolimab group due to pneumonitis. The addition of sabatolimab to hypomethylating agents in this study did not result in a significant improvement in complete response rates or progression-free survival. Sabatolimab had a manageable safety in most patients with higher-risk myelodysplastic syndromes. A randomised phase 3 trial is ongoing to assess the potential benefit of sabatolimab plus azacitidine on overall survival in this setting. Novartis Pharmaceuticals.

Primary Analysis and Results of Bendamustine, Rituximab, and Venetoclax (BR-VEN) for Initial Treatment of Mantle Cell Lymphoma in Subjects over 60 Years of Age (PrE0405)

Background Mantle cell lymphoma (MCL) is an incurable form of aggressive non-Hodgkin lymphoma. Treatment choice at diagnosis is based on tolerability of cytarabine and high-dose chemotherapy. With a median age of 60-70 years, many patients are ineligible for aggressive treatment. Bendamustine and rituximab (BR) is a reasonable treatment option (E1411, Smith MR et al. ASH 2022) for this patient population and venetoclax (VEN) has shown pre-clinical evidence of synergy with chemoimmunotherapy. PrECOG 0405 was designed to evaluate the addition of VEN to BR in previously untreated patients with MCL aged over 60 years. Methods Eligible patients included those that were previously untreated and diagnosed with MCL as defined as the presence of t(11;14) by FISH or cyclin D1 expression by IHC. Patients must have been at least 60 years of age or older on D1C1 of therapy with a good performance status (ECOG 0-2). Adequate marrow and organ function was required, specifically a creatinine clearance of ≥ 40 mL/min. Treatment administration is summarized in Figure 1. Dose of bendamustine was either 90mg/m 2 D1&amp;2; or, for subjects over the age of 75 years, 70mg/m 2 was allowed per investigator discretion. VEN was dose escalated during Cycle 1 to 200mg. At the time of C2, BR was repeated and VEN was also escalated to 400mg. With C2-6, VEN 400mg PO daily was given D1-10 only. Primary endpoint was PET-negative complete response (CR) rate at end of treatment (EOT) by Lugano Criteria. A negative bone marrow biopsy was required to confirm CR if involved at screening. Minimal residual disease (MRD) by next-generation sequencing was performed at the EOT. Maintenance rituximab was encouraged per investigator discretion. This was a single arm study with an original accrual goal of 53 subjects to detect a 15% improvement in CR rate compared to historical data. However, due to slow study accrual during COVID pandemic and preliminary efficacy data from E1411 study, the statistical parameters were updated after 25 subjects had been accrued. The revised accrual goal was 33 patients to obtain 32 eligible and treated patients, which provided 81.8% statistical power to detect a 17% difference in CR rate (from 60% [E1411 data] to 77%) using an exact binomial test with a 1-sided alpha of 11.6%. This combination regimen will be considered promising if 23 or more (out of 32) patients attain CR. Results From January 2020 to March 2022, 33 subjects enrolled and were treated on study. Subject characteristics are listed in Table 1. Seven (21%) unique subjects were treated with 70mg/m 2 of bendamustine during induction cycles. Laboratory tumor lysis syndrome (TLS) was seen in 2/33 during C1 only; clinical TLS was not seen. Treatment was generally well tolerated with treatment-related adverse events (TRAE) of Grade ≥3 and occurring in &amp;gt;10% of subjects being neutropenia (n=5, 15%), thrombocytopenia (n=5, 15%) and lymphopenia (n=9, 27%). Other common non-hematologic TRAE of all grades were nausea/vomiting (n=26, 79%), diarrhea (n=10, 30%), and fatigue (n=17, 52%). There were 4 (12%) instances of COVID-19/COVID-19 pneumonia considered treatment related. Dose adjustments and delays for any drug occurred in 36% and 67% of subjects respectively. 22/33 (66.7%) subjects completed 6 cycles of BR-VEN. Maintenance rituximab was administered in 19/33 (57.6%) of subjects. Overall response rate was 97% (32/33) and PET-negative bone marrow biopsy confirmed CR Rate at EOT was 85% (28/33), achieving the primary endpoint (≥23 CRs). MRD at EOT is under analysis. With a median survival follow up of 21.5 months (mo), Median PFS and OS were not reached; estimated 2-year PFS and OS was 69.7% and 81.1% respectively. During follow up, there have been 6 deaths, 4 from COVID-19 (all in remission), one from influenza A (in remission), and one from disease progression (non-responding pt). There have been 2 other progression events who are alive. Conclusions BR-VEN was generally well-tolerated in this older patient population though GI toxicities were common. With a PET-negative CR rate of 85%, the combination is promising but longer follow-up is needed. There was a competing risk of death related to upper respiratory viruses identified, mostly COVID-19, as has been seen in other BR-based protocols during the COVID-19 pandemic. MRD analysis and survival data will be updated.

Ibrutinib Combined with Venetoclax in Patients with Relapsed/Refractory Mantle Cell Lymphoma: Primary Analysis Results from the Randomized Phase 3 Sympatico Study

Background: Ibrutinib (Ibr) is a once-daily Bruton tyrosine kinase (BTK) inhibitor approved in multiple regions for patients (pts) with mantle cell lymphoma (MCL) who have received ≥1 prior therapy. Venetoclax (Ven) is a BCL-2 inhibitor approved in the US for pts with chronic lymphocytic leukemia and previously untreated acute myeloid leukemia. Ibr and Ven have distinct and complementary modes of action, and the combination has shown promising clinical activity in early phase studies in MCL (Tam, N Engl J Med 2018; Wang, J Hematol Oncol 2021). Here, we report the primary analysis results from the multinational, randomized, double-blind, phase 3 SYMPATICO (NCT03112174) study comparing Ibr+Ven vs Ibr + placebo (Pbo) in pts with relapsed/refractory (R/R) MCL. Methods: Pts aged ≥18 y with R/R MCL after 1-5 prior therapies were randomly assigned 1:1 to receive oral Ibr 560 mg once daily concurrently with oral Ven (standard 5-wk ramp-up to a target dose of 400 mg once daily) or Pbo for 2 y, followed by single-agent Ibr until progressive disease (PD) or unacceptable toxicity. Randomization was stratified based on ECOG PS, prior lines of therapy, and tumor lysis syndrome (TLS) risk based on tumor burden and CrCl. The primary endpoint was progression-free survival (PFS) by investigator (INV) assessment using Lugano criteria; pts without PD or death were censored at the last non-PD assessment (per global censoring rules). Additional sensitivity analyses included PFS assessment by independent review committee (IRC) and censoring per US FDA rules (Table). Key secondary endpoints were tested hierarchically in the following order: complete response (CR) rate by INV assessment, time to next treatment (TTNT), overall survival (OS, interim analysis), and overall response rate (ORR) by INV assessment. Results: A total of 267 pts were enrolled and randomly assigned to receive Ibr+Ven (n=134) or Ibr+Pbo (n=133). Median age was 68 y; 96% of pts had an ECOG PS of 0-1, 17% had ≥3 prior lines of therapy, and 22% were at increased risk for TLS. At baseline, pts in the Ibr+Ven vs Ibr+Pbo arms had median ages 69 vs 67 y, high-risk simplified MCL International Prognostic Index score 38% vs 31%, bulky disease ≥5 cm 46% vs 40%, bone marrow involvement 46% vs 41%, splenomegaly 31% vs 25%, and TP53 mutated 30% vs 28%; other baseline characteristics were generally similar between arms. With a median time on study of 51.2 mo, median PFS by INV assessment was significantly longer with Ibr+Ven vs Ibr+Pbo (31.9 vs 22.1 mo), with a hazard ratio (HR) of 0.65 (95% CI, 0.47-0.88; stratified log-rank P=0.0052) (Figure). PFS rates at 24 mo were 57% and 45% with Ibr+Ven and Ibr+Pbo, respectively. PFS benefit with Ibr+Ven vs Ibr+Pbo was generally consistent across prespecified subgroups, including those with blastoid variant or TP53-mutated MCL. Sensitivity analyses of PFS were consistent with the primary analysis (Table). Ibr+Ven significantly improved CR rates (54% vs 32%) and TTNT (median not reached [NR] vs 35.4 mo); at the current 51.2 mo median follow-up, median OS was 44.9 mo with Ibr+Ven vs 38.6 mo with Ibr+Pbo (HR 0.85 [95% CI, 0.62-1.19]) (Table). Median duration of treatment was 22.2 mo for the Ibr+Ven arm and 17.7 mo for the Ibr+Pbo arm; at the time of analysis, 30% of pts in the Ibr+Ven arm and 20% of pts in the Ibr+Pbo arm remained on single-agent Ibr. Grade ≥3 adverse events (AEs) occurred in 84% of pts with Ibr+Ven vs 76% with Ibr+Pbo; the most frequent (occurring in ≥5% of pts) were neutropenia (31% vs 11%), pneumonia (13% vs 11%), thrombocytopenia (13% vs 8%), anemia (10% vs 3%), diarrhea (8% vs 2%), leukopenia (7% vs 0%), MCL (7% vs 12%), atrial fibrillation (5% vs 5%), COVID-19 (5% vs 1%), and hypertension (4% vs 9%). Serious AEs occurred in 60% of pts in each arm. No clinical TLS occurred; laboratory TLS occurred in 5% and 2% of pts in the Ibr+Ven and Ibr+Pbo arms, respectively. COVID-19 deaths occurred in 10 pts in each arm and had no meaningful impact on PFS or OS HRs. Conclusion: The Ibr+Ven combination demonstrated a statistically significant improvement in PFS compared with Ibr+Pbo in pts with R/R MCL; CR rates and TTNT were also significantly improved with Ibr+Ven. OS was numerically but not significantly improved at this interim analysis. The safety profile of Ibr+Ven was consistent with known AEs for each agent, with no new safety signals observed. Overall, these results demonstrate a favorable benefit-risk profile for Ibr+Ven in pts with R/R MCL.

Phase 1b/2 study of combination 177Lu girentuximab plus cabozantinib and nivolumab in treatment naïve patients with advanced clear cell RCC.

TPS4605 Background: Complete response (CR) is still a rare event in patients with advanced clear cell renal cell carcinoma (ccRCC). The combination of nivolumab plus cabozantinib was recently approved for the first-line treatment of ccRCC based on the CheckMate 9ER phase III study demonstrating improved progression-free survival (PFS) and objective response rate (ORR) in comparison to sunitinib. However, the CR rate was only 9%. Since the anti-tumor effects of immune checkpoint inhibitors are dependent on the presence of activated tumor-infiltrating T cells, drugs that could synergize with T cells’ anti-tumor activity can allow us to improve CR rates. Activation of the cGAS-STING pathway, the master regulator of anti-tumor immunity which is induced by radiation-induced DNA damage, is one promising mechanism that has been investigated. Many studies have shown that radiation treatment augments immune checkpoint inhibition. However, it is not always possible to radiate all metastatic lesions. Therefore, targeted peptide receptor radionuclide therapies (PRRT), have been developed by conjugating radioisotopes to receptor binding analogs targeting specific cancer cell surface proteins, thereby delivering targeted radiation to cancer cells in the body with minimal damage to surrounding healthy cells. 177Lu girentuximab is the first antibody-radioisotope designed for ccRCC, targeting carbonic anhydrase IX-expressing cells, which includes &gt; 90% of ccRCC. It has been tested in metastatic ccRCC as a single agent and shown to be safe and effective in stabilizing disease in 57% of pts. In this study, we hypothesize that 177Lu girentuximab-induced DNA damage will potentiate the STING pathway, and this activation will synergize with nivolumab and cabozantinib to promote trafficking and infiltration of activated T cells to tumors and achieve higher CR rates. Methods: Up to 100 patients with treatment naïve, biopsy-proven ccRCC with adequate organ/marrow function with ≥1 evaluable lesion by RECIST 1.1 will be enrolled. A 5-patient safety lead-in will evaluate myelosuppression. Ongoing safety, and futility monitoring will employ a Bayesian approach. The sample size was chosen for reasonable operating characteristics to distinguish a CR rate of 18% as better than 9% using a beta(0.09, 0.91) prior. Secondary endpoints are objective response, PFS by RECIST 1.1, and overall survival. 177Lu-girentuximab 1480 MBq/m2 (61% of single agent MTD) will be administered every 12 weeks for up to 3 treatment cycles. After the first cycle, nivolumab and cabozantinib will be added starting with the second cycle at standard dose. To explore the effects of the combination therapy on inducing activated T cell infiltration, patients will undergo pre/post-treatment PET scan with [18F]F-AraG radiotracer as well as biopsies for single cell, spatial transcriptomics and proteomics studies.

Effect of treatment of residual disease after immunotherapy-based combinations on complete response rate in metastatic renal cell carcinoma.

601 Background: Immunotherapy (IO) has revolutionized the management of metastatic renal cell carcinoma (mRCC) by improving survival, overall response and complete response (CR) rates. CR is achieved in 11 to 17% with the different PD-1-based IO combinations in first-line setting of mRCC. However, local treatment of residual disease after systemic treatment exposure may improve CR rates. We performed a retrospective study to characterize patients (pts) in CR with systemic therapy alone or combined to an ablative approach of residual disease. Methods: We included all consecutive mRCC pts treated with mRCC in first-line treatment with IO combination with IO or TKI, either alone or with local treatment at the Institut de Cancérologie Strasbourg Europe. Pts were characterized according to IMDC risk group. Radiologic response was defined according to RECIST v1.1. Results: We enrolled 80 pts with mRCC between 5/2015 and 5/2022; median age was 68 (41-89) years; 75% male; 36 pts (45%) had prior nephrectomy; IMDC risk group: 12 favorable (15%), 50 intermediate (63%), 18 poor risk pts (22%), respectively; 47 pts (59%) received IO + IO, 24 (30%) received IO + TKI and 9 pts (11%) received another IO-based therapy; 35 pts (44%) achieved partial response, 23 pts (29%) stable disease, 13 pts progressive disease and 9 pts achieved CR (11%) as best response with systemic therapy alone; 10 pts out of 35 PR pts achieved CR by adding local treatment on residual disease. Among CR pts: 5 out of 19 pts had a component of sarcomatoid histology; median age was 60 years. Characteristics of pts with CR are reported in the table. Median duration of IO exposure before local therapy was 13 months. Residual disease resected sites included kidney (N = 6), lymph node (N = 4), lung metastasis (N = 2) and liver metastasis (N = 1). Local treatment was surgery for 9 pts and liver thermoablation for 1 patient. Conclusions: The resection of residual disease after first line IO-based therapy in mRCC improves CR rates (from 11% up to 24%). This approach should be considered as an option for a selected population. Prospective trials assessing this strategy should be performed in the future. Characteristics of patients in CR. [Table: see text]

Phase 1b/2 study of combination 177Lu girentuximab plus cabozantinib and nivolumab in treatment naïve patients with advanced clear cell RCC.

TPS749 Background: Complete response (CR) is still a rare event in patients with advanced clear cell renal cell carcinoma (ccRCC). The combination of nivolumab plus cabozantinib was recently approved for the first-line treatment of ccRCC based on the CheckMate 9ER phase 3 study demonstrating improved progression-free survival (PFS) and objective response rate (ORR) in comparison to sunitinib. However, the CR rate was only 9%. Since the anti-tumor effects of immune checkpoint inhibitors are dependent on the presence of activated tumor-infiltrating T cells, drugs that could synergize with T cells’ anti-tumor activity can allow us to improve CR rates. Activation of the cGAS-STING pathway which is induced by radiation-induced DNA damage, is one promising mechanism that has been investigated. Many studies have shown that radiation treatment augments immune checkpoint inhibition. However, it is not always possible to radiate all metastatic lesions. Therefore, targeted peptide receptor radionuclide therapies, have been developed by conjugating radioisotopes to receptor binding analogs targeting specific cancer cell surface proteins, thereby delivering targeted radiation to cancer cells in the body with minimal damage to surrounding healthy cells. 177Lu girentuximab is the first antibody-radioisotope designed for ccRCC, targeting carbonic anhydrase 9-expressing cells, which includes &gt;90% of ccRCC. It has been tested in metastatic ccRCC as a single agent and shown to be safe and effective in stabilizing disease in 57% of pts. In this study, we hypothesize that 177Lu girentuximab-induced DNA damage will potentiate the STING pathway, and this activation will synergize with nivolumab and cabozantinib to promote trafficking and infiltration of activated T cells to tumors and achieve higher CR rates. Methods: Up to 100 patients with treatment naïve, biopsy-proven ccRCC with adequate organ/marrow function with ≥1 evaluable lesion by RECIST 1.1 will be enrolled. A 5-patient safety lead-in will evaluate myelosuppression. Ongoing safety, and futility monitoring will employ a Bayesian approach. The sample size was chosen for reasonable operating characteristics to distinguish a CR rate (primary endpoint) of 18% as better than 9% using a beta(0.09, 0.91) prior. Secondary endpoints are ORR, PFS by RECIST 1.1, and overall survival. 177Lu-girentuximab 1480 MBq/m2 (61% of single agent MTD) will be administered every 12 weeks for up to 3 cycles. Starting with the second cycle, nivolumab and cabozantinib will be added at standard dose. To explore the effects of the treatment on inducing activated T cell infiltration, patients will undergo pre/post-treatment PET scan with [18F]F-AraG radiotracer as well as biopsies for single cell, spatial transcriptomics and proteomics studies. This investigator initiated trial is supported by Telix Pharmaceuticals and DOD grant W81XWH-22-1-0456.

YTB323 (Rapcabtagene Autoleucel) Demonstrates Durable Efficacy and a Manageable Safety Profile in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Phase I Study Update

Background: CD19-directed CAR-T cell therapies (tx) have shown efficacy in patients (pts) with B-cell malignancies. However, many pts fail to respond or experience disease relapse after initial response. YTB323 (rapcabtagene autoleucel) is an autologous CD19-directed CAR-T cell tx generated by the innovative T-Charge™ platform, which produces CAR-T cells by a rapid manufacturing process (2 days) preserving T-cell stemness. This methodology is expected to increase CAR-T cell persistence and expansion and yield higher efficacy and a manageable safety profile. Here we present efficacy and safety, dose exposure, and biomarker analyses for rapcabtagene autoleucel in adults with r/r DLBCL in the ongoing Phase I, multicenter, dose-escalation study (NCT03960840). Methods: Eligible pts had r/r DLBCL after ≥2 lines of prior tx, measurable disease at enrollment, and ECOG 0-1. Pts received single-dose rapcabtagene autoleucel at targeted dose level (DL) 1 (2.5×106 CAR+ cells), DL2 (12.5×106 CAR+ cells), DL3 (25×106 CAR+ cells), or DL4 (40×106 CAR+ cells). Primary endpoints characterized safety and dose-limiting toxicities to identify a recommended dose. Secondary endpoints include response rate by local investigator assessment and cellular kinetics. Results: As of March 31, 2022, 45 pts with r/r DLBCL received rapcabtagene autoleucel: 4 at DL1, 28 at DL2, 7 at DL3, and 6 at DL4. Median age was 64.8 y, 67% received 2 prior lines of tx, and 29% had prior autologous stem cell transplant. Median (range) time since most recent relapse/progression was 2.8 (1.4-81.8) mo. Pts were followed for a median (range) of 10 (0.3-29) mo. Complete response (CR) rate at DL2 was 65%. CR at DL2, excluding pts in CR before rapcabtagene autoleucel (due to either a late effect of prior tx or bridging chemotherapy), was 61%. Responses at DL2 were durable, with CR rates of 63% (12/19) at 3 mo and 69% (11/16) at 6 mo (Figure 1). Median duration of response at DL2 was not reached. Of 45 pts evaluable for safety, 96% reported 1 adverse event (AE) of any grade (Gr) and 89% had ≥1 AE Gr ≥3. Cytokine release syndrome (CRS) was experienced by 15 pts (33%): 1 at DL1, 10 at DL2, 2 at DL3, and 2 at DL4. One DL2 pt (4%) experienced Gr 4 CRS. CRS was managed with tocilizumab, corticosteroids, and vasopressors in 7 (70%), 3 (30%), and 1 (10%) pts at DL2, respectively, and 1 DL3 pt (50%) received tocilizumab. Median (range) time to CRS onset was 9 (1-36) d and resolution was 5 (1-18) d. Five pts (11%) had immune effector cell-associated neurotoxicity syndrome (ICANS) events: 3 at DL2 and 2 DL4. Two DL2 pts (7%) experienced Gr 3 ICANS (no pts experienced Gr 4-5). Median (range) time to onset and resolution of ICANS was 16 (6-28) and 16 (1-36) d, respectively. ICANS management was based on dexamethasone, methylprednisolone, and anakinra in 2 (67%), 1 (33%), and 1 (33%) pts at DL2, respectively, and 1 DL4 pt (50%) received dexamethasone. Median time to peak rapcabtagene autoleucel expansion was delayed compared with tisagenlecleucel: 16 d at DL2 vs 9 d in JULIET. At a 25-fold lower dose, rapcabtagene autoleucel expansion at DL2 was comparable by qPCR to tisagenlecleucel expansion in JULIET. Expansion increased from DL1 to DL2 with no further increases at higher doses. Data from DL2 show CAR transgene was detectable by qPCR in 1 out of 2 pts with 12 mo follow-up. scRNAseq analysis shows the rapcabtagene autoleucel manufacturing process preserves T-cell fitness by retaining the composition of cell populations from apheresis to final product through the short manufacturing time. scRNAseq analysis also suggests that certain characteristics of the final product composition may lead to improved CR rates at 3 mo. B-cell aplasia (≤50 CD19+ cells/μL) was established before/after rapcabtagene autoleucel in all pts. In responders, B-cell aplasia persisted for ≥8 mo. Conclusions: Rapcabtagene autoleucel is a potent new CD19-directed CAR-T cell tx with distinct cellular kinetics, durable efficacy, and a manageable safety profile. DL2 (12.5×106) CAR+ viable T cells is the recommended dose for Phase III studies, based on the CR rate, favorable safety profile, and cellular kinetics. Updated results with expanded cellular kinetics and biomarker analyses will be presented at the meeting. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Phase II Trial of TGFβ Type I Receptor Inhibitor, Galunisertib, plus Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer

<h3>Purpose/Objective(s)</h3> Transforming growth factor beta (TGFβ) is an immunosuppressive cytokine upregulated in colorectal cancer. Preclinical data demonstrated improved response to chemoradiation with TGFβ blockade in colorectal adenocarcinoma. Here we report the results of our single arm Phase II study combining the TGFβ type I receptor kinase inhibitor, galunisertib, with neoadjuvant chemoradiation in patients with locally advanced rectal adenocarcinoma. <h3>Materials/Methods</h3> Eligible patients had T3+ or N+ rectal adenocarcinoma planned for surgical resection. Enrolled patients completed a 14-day course of galunisertib, followed by chemoradiation with continuous infusion 5-fluorouracil or capecitabine with radiation to 50.4-54Gy in 28-30 fractions. On day 30, patients underwent another 14-day course of galunisertib concurrent with ongoing chemoradiation. Five to nine weeks after completing neoadjuvant therapy, patients underwent response assessment. Those with complete response by physical exam, proctoscopy, and MRI, could opt for non-operative management and proceed to mFOLFOX6. Those with less than a complete response underwent surgical resection. The primary endpoint was complete response (CR) rate, which was a composite of pathologic complete responses in those patients who proceeded to surgery, and clinical complete responses maintained at 1 year after completion of therapy for those who chose non-operative management. Using a Simon Two-Stage approach with 90% power and α=0.05, to detect a 20% improvement in complete response rate compared to historical control (15% vs 35%); we reject the null hypothesis if ≥10/38 patients have a CR. 38 patients were enrolled with 35 patients evaluable. <h3>Results</h3> Median age was 51y, 68% of patients were male, 87% of patients were Stage III, 97% of patients were node-positive, and 97% were proficient in mismatch repair. 95% of patients completed study therapy. Toxicity attributed to galunisertib was Grade 1-2. 28 patients went to surgery, with a mean neoadjuvant rectal (NAR) score (NAR = 5pN-3(cT-pT)+12]²/9.61) of 11.29, and pathologic complete response (pCR) in 7 patients. 7 patients underwent non-operative management, with 5 achieving clinical complete response (cCR) at 1 year. Therefore, complete responses were observed in 12 patients. Peripheral immune monitoring revealed percent change in CD3+CD4-CXCR3+ T cells and activated effector memory CD8 T cells correlated with response to therapy. Decreased phospho-Smad2 in day 15 biopsies correlated with treatment response. 2y PFS and OS were 81.5% and 97%. <h3>Conclusion</h3> The addition of TGFβ inhibition to neoadjuvant chemoradiation in locally advanced rectal cancer markedly improved response to therapy, was well tolerated, and warrants further investigation. Clinical Trial Information: NCT02688712.

A phase II trial of TGFβ type I receptor inhibitor, galunisertib, plus neoadjuvant chemoradiation in patients with locally advanced rectal cancer.

3617 Background: Transforming growth factor beta (TGFβ) is an immunosuppressive cytokine upregulated in colorectal cancer. Preclinical data demonstrated improved response to chemoradiation with TGFβ blockade in colorectal adenocarcinoma. Here we report the results of our single arm Phase II study combining the TGFβ type I receptor kinase inhibitor, galunisertib, with neoadjuvant chemoradiation in patients with locally advanced rectal adenocarcinoma. Methods: Eligible patients had T3+ or N+ rectal adenocarcinoma planned for surgical resection. Enrolled patients completed a 14-day course of galunisertib, followed by chemoradiation with continuous infusion 5-fluorouracil or capecitabine with radiation to 50.4-54Gy in 28-30 fractions. On day 30, patients underwent another 14-day course of galunisertib concurrent with ongoing chemoradiation. Five to nine weeks after completing neoadjuvant therapy, patients underwent response assessment. Those with complete response by physical exam, proctoscopy, and MRI, could opt for non-operative management and proceed to mFOLFOX6. Those with less than a complete response underwent surgical resection. The primary endpoint was complete response rate (CR), which was a composite of pathologic complete responses in those patients who proceeded to surgery, and clinical complete responses maintained at 1 year after completion of therapy for those who chose non-operative management. Using a Simon Two-Stage approach with 90% power and α = 0.05, to detect a 20% improvement in complete response rate compared to historical control (15% vs 35%); we reject the null hypothesis if ≥10/38 patients have a CR. 38 patients were enrolled with 35 patients evaluable. Results: Median age was 51y, 68% of patients were male, 87% of patients were Stage III, 97% of patients were node-positive, and 97% were proficient in mismatch repair. 95% of patients completed study therapy. Toxicity attributed to galunisertib was Grade 1-2. 28 patients went to surgery, with a mean neoadjuvant rectal (NAR) score (NAR = 5pN-3(cT-pT)+12]2/9.61) of 11.29, and pCR in 7 patients. 7 patients underwent non-operative management, with 5 achieving cCR at 1 year. Therefore, complete responses were observed in 12 patients. Peripheral immune monitoring revealed percent change in CD3+CD4-CXCR3+ T cells and activated CD8EM T cells correlated with response to therapy. 2y PFS and OS were 81.5% and 97%. Conclusions: The addition of TGFβ inhibition to neoadjuvant chemoradiation in locally advanced rectal cancer markedly improved response to therapy, was well tolerated, and warrants further investigation. Clinical trial information: NCT02688712.

First Line Chemo-Free Therapy with the BRAF Inhibitor Vemurafenib Combined with Obinutuzumab Is Effective in Patients with Hcl

First Line Chemo-Free Therapy with the BRAF Inhibitor Vemurafenib Combined with Obinutuzumab Is Effective in Patients with Hcl

Multi-Institutional Comparison of SC-TNT and LC-TNT for Rectal Cancer Non-Operative Management

Recent data support the use of total neoadjuvant therapy (TNT) for treatment of locally advanced rectal cancer (LARC), although the optimal TNT regimen and therapy sequence is unclear for non-operative management (NOM). We performed a multi-institutional comparison of short-course radiation (SCRT) followed by consolidation chemotherapy (SC-TNT) versus long-course chemoradiation (CRT) preceded by induction chemotherapy (LC-TNT), after adoption of NOM at both institutions.The records of 187 patients with cT2-4N0-2 rectal cancer treated between 2016-2020 with TNT at two academic institutions were reviewed under an IRB-approved protocol. The SC-TNT cohort (institution 1) included 85 patients treated with SCRT (25-30 Gy in 5 fx) followed by FOLFOX/CAPOX (n = 82) or capecitabine (n = 3). The LC-TNT cohort (institution 2) included 102 patients treated with FOLFOX/CAPOX followed by CRT (45-56 Gy at 1.8-2 Gy/fx) with concurrent fluoropyrimidine-based chemotherapy. Patients with a clinical complete response (cCR) were offered NOM. The rates of cCR were compared between SC- and LC-TNT. Disease-free survival (DFS) was compared using the log-rank test. To account for any differences in NOM selection between institutions, local-only tumor regrowth was censored from DFS if salvaged with R0 resection, and the overall complete response (CR) rate, defined as cCR + pCR rate for patients undergoing surgery, was assessed. Multivariate analysis (MVA) was performed with logistic and Cox regression to determine factors associated with CR and DFS, respectively.The median age at diagnosis was 60 and 54 years for SC-TNT and LC-TNT cohorts, respectively (P = 0.002). All other characteristics including performance status, tumor location, and clinical stage were balanced. The median duration of neoadjuvant FOLFOX/CAPOX chemotherapy was 105 vs 98 days for the SC-TNT and LC-TNT cohorts, respectively (P = 0.001). The median follow-up was 27 months. The cCR rate was higher in the SC-TNT cohort (44/85, 52.8% vs 21/102, 20.6%, P < 0.001), with a trend for improved CR rate for SC-TNT (54.1% vs 40.2%, P = 0.057). On MVA, use of SC-TNT was associated with improved CR (HR = 2.24, 95% CI: 1.13-4.45, P = 0.021). Among patients undergoing NOM, 33/39 patients (84.6%) in the SC-TNT group and 10/17 patients (58.8%) in the LC-TNT group (P = 0.27) were free from local recurrence at 1 year. Two-year DFS was 93.4% and 95.4% for the SC-TNT and LC-TNT cohorts with improved DFS on log-rank test for LC-TNT (P = 0.023), but no DFS difference on MVA between SC-TNT and LC-TNT (HR = 2.29, 95% CI: 0.8-6.51, P = 0.121).SC-TNT demonstrated a greater rate of cCR compared to LC-TNT, without DFS difference on MVA. Although future studies are warranted to compare SC-TNT with a CRT and consolidative chemotherapy TNT approach, our data support SC-TNT as a suitable regimen for LARC NOM.

Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis

BackgroundTo provide pooled longer term data from three groups of a phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC), and to determine duration of...

Treatment outcomes of cohesin complex-mutant myelodysplastic syndrome and acute myeloid leukemia.

e19007 Background: Mutations in the genes STAG1, STAG2, SMC1A, SMC3, and RAD21 which are part of the cohesin complex are recurrent in myelodysplastic syndrome and acute myeloid leukemia. The cohesin complex is involved in sister chromatid attachment during cell division and in DNA loop formation bringing enhancers and genes together. Prognosis and treatment efficacy for this subgroup has not been well studied in MDS or AML. We evaluated the treatment outcomes of a subgroup with cohesin mutations from a database of MDS and AML patients at the University of Massachusetts. Methods: We performed a retrospective analysis of adult patients with a new diagnosis of AML and/or MDS from 2015-2019 in the University of Massachusetts Leukemia Registry. Fisher’s exact test was used to compare initial response to treatment via induction chemotherapy or hypomethylating agents. Kaplan-Meier curves for overall survival were compared using the log-rank test. We considered &lt; 5% blasts by morphology to be complete remission (regardless of hematologic recovery). Four patients who did not undergo treatment were excluded from treatment and survival analysis. Results: A total of 19 patients had mutations in a cohesin complex gene with one patient having mutations in both STAG2 and SMC1A. The cohesin complex mutation frequency was 9.95% (19 out of 191 patients) with STAG2 representing 70% of the mutations. First-line induction chemotherapy resulted in an improved rate of complete remission 83.3% compared to hypomethylating agents 0% (p = 0.002). For AML patients alone, there was improvement in complete response rate for induction chemotherapy vs. hypomethylating agents (p = 0.048). There was no overall survival benefit for induction chemotherapy compared to hypomethylating agents (44.4% vs 41.7% probability of survival at 2 years) with p = 0.87. Excluding the MDS patients, there was still no difference in overall survival with p = 0.63. Conclusions: In this retrospective analysis of cohesin complex-mutant MDS and AML, induction chemotherapy resulted in significantly improved complete remission rates compared to hypomethylating agents. There was no overall survival benefit. We also found one patient with simultaneous mutations in two cohesin genes while cohesin mutations were previously reported to be mutually exclusive. Further work looking at additional samples may be able to show induction chemotherapy is the treatment of choice for cohesin mutant AML.[Table: see text]

Benefit From Adjuvant Radiation Therapy In Oropharyngeal Cancer Patients That Underwent Induction Chemotherapy Plus Surgery

This retrospective study aims to evaluate the outcome of patients with tonsil squamous cell carcinoma (SCC) treated with induction chemotherapy (ICT) followed by surgery, with or without external beam radiation therapy (EBRT), to assess the impact of EBRT regarding human papillomavirus (HPV) status. Between 1997 and 2017, 99 patients with tonsil SCC underwent ICT followed by surgical resection. After surgery, 79 patients had adjuvant EBRT (Group 1), while 16 patients (free margins, N0 or N1) have not received radiotherapy EBRT (Group 2). Median follow-up was 71 months. HPV status was positive in 42 patients (43%), negative in 50 patients (57%). After ICT, pathological complete response (CR) was reported for the primary site or lymph nodes in 25 patients (27%) and 53 patients (58%) respectively. HPV-positive status was the only prognosis factor associated with improved CR after ICT (p = 0.04). Five-year progression-free survival (PFS) in this cohort, group 1 and group 2 were 68% (IC95% = 59 – 79), 72/% (IC95% = 62 – 83), and 54% (IC95% = 36 – 81) respectively (p = 0.04). In multivariate analysis, prognosis factors associated with improved PFS were: primary and nodal CR after ICT (p < 0.001), EBRT (p < 0.001), and HPV-positive status (p = 0.02). Five-years OS in this cohort, group 1 and group 2 were 69% (IC95% = 61 – 80), 64% (IC95% = 54 – 76), and 90% (IC95% = 78 – 100) respectively (p = 0.7). In multivariate analysis, the only prognosis factor related with a longer OS was pN0 status after ICT (p < 0.001). In this series, HPV-positive status was associated with improved CR rates after ICT. Still, PFS was decreased in patients that did not underwent radiation therapy after ICT plus surgery, independently from HPV-status or response after ICT.

Chemotherapy-Induced Nausea and Vomiting (CINV) with GI Cancer Chemotherapy: Do We Need CINV Risk Score Over and Above Antiemetic Guidelines in Prescribing Antiemetic Regime?

Background Various predictive models have been developed which incorporates patient risk factors into the selection of optimal antiemetic therapy, one of which is chemotherapy-induced nausea and vomiting (CINV) risk scoring system developed by Multinational Association of Supportive Care in Cancer (MASCC). Patients and Methods Consecutive patients with gastrointestinal malignancy who had not received previous chemotherapy were eligible for enrollment in the study if they were scheduled to receive at least one cycle of chemotherapy. The CINV risk assessment tool was used to collect the study data and to assess CINV risk score. Results Ninety-eight patients fulfilling the eligibility criteria were included in this study, out of which 57% were males, median age was 48 years (range: 28–77). Colorectal cancer (32.7%) was the most common diagnosis followed by gastric cancer (27.6%). Gemcitabine/cisplatin and CAPOX regimen were the most common regimen being administered in 19.4% each. As per MASCC guidelines, 19.4% patients received highly emetogenic chemotherapy, 69.4% moderately emetogenic chemotherapy, while 11.2% received regimen with low emetogenicity. CINV risk module characterized 52% patients to have high risk for CINV, while 48% to have low risk of CINV, thus, 52% had the discrepancy in risk assigned by two methods, and this was statistically significant ( p = 0.025). In subgroup analysis, although patient cohort with acute nausea had no statistically significant discrepancy ( p = 0.123), but statistically significant discrepancy was found in patient cohort with delayed nausea ( p = 0.001), acute ( p = 0.038), and delayed ( p < 0.001) vomiting. Conclusion A significant percentage of patients who receive chemotherapy continue to experience nausea and vomiting despite receiving antiemetic treatment as per standard guidelines. The study generates a hypothesis for future large randomized studies looking at change in antiemetic prophylaxis based on CINV risk tool, leading to improvement in complete response rates of acute and delayed CINV.

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity.

Axicabtagene ciloleucel (axi-cel) was approved by the Food and Drug Administration for relapsed aggressive B-cell non-Hodgkin lymphoma in part on the basis of durable remission rates of approximately 40% in a clinical trial population. Whether this efficacy, and the rates of toxicity, would be consistent in a postcommercial setting, with relaxed eligibility criteria and bridging therapy, is unknown. This study describes the efficacy and safety correlates and outcomes in this setting. One hundred twenty-two patients from 7 medical centers in the United States were treated with axi-cel and were included in a modified intent-to-treat (mITT) analysis. Seventy-six patients (62%) were ineligible for the ZUMA-1 trial. Response and toxicity rates, duration of response (DOR), survival, and covariates are described on the basis of the mITT population. Correlative studies on blood and tumor samples were performed to investigate potential biomarkers of response and resistance. Median follow-up was 10.4 months. In the mITT population, the best overall and complete response (CR) rates were 70% and 50%, respectively. Median DOR and progression-free survival (PFS) were 11.0 and 4.5 months in all patients and were not reached (NR) in CR patients. Median overall survival (OS) was NR; 1-year OS was 67% (95% CI, 59% to 77%). Although response rates were similar in the ZUMA-1-eligible and ZUMA-1-ineligible groups (70% v 68%), there was a statistically significant improvement in CR rate (63% v 42%, P = .016), DOR (median, NR v 5.0 months; P = .014), PFS (median, NR v 3.3 months; P = .020), and OS (1-year OS, 89% v 54%; P < .001) in patients who were ZUMA-1 eligible. Rates of grade ≥ 3 cytokine release syndrome and neurotoxicty were 16% and 35%, respectively. Axi-cel yields similar rates of overall response and toxicity in commercial and trial settings, although CR rates and DOR were more favorable in patients eligible for ZUMA-1.

Efficacy of acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: a multi-center, single-blind, randomized, sham-controlled clinical research

BackgroundChemotherapy-induced nausea and vomiting (CINV) is a common and distressing side effect. We conducted this clinical trial to compare the effectiveness of true acupuncture vs. sham acupuncture in controlling chemotherapy-induced nausea and vomiting (CINV) among patients with advanced cancer.MethodsA total of 134 participants were randomly allocated into true acupuncture (TA) (n = 68) and sham acupuncture (SA) (n = 66) groups. Participants in both groups received acupuncture session twice on the first day of chemotherapy, and once consecutively on the following 4 days. The primary outcome was using the Common Terminology Criteria for Adverse Events (CTCAE) to assess CINV. The secondary outcome measures were the Eastern Cooperative Oncology Group score (ECOG), Simplified Nutritional Appetite Questionnaire (SNAQ), and Hospital Anxiety and Depression scale (HADS).ResultsCompared to the SA group, the TA group didn’t show significant improvement in complete response rates of chemotherapy-induced nausea and vomiting (all P > 0.05). However, the TA group could modestly reduce the severity of nausea (from day-3 to day-21, P < 0.05) or vomiting (from day-4 to day-21, P < 0.05), which is notably superior to the control group. Besides, TA promoted the nutritional status of patients with a significantly higher score comparing to the SA group on day 14 (21.82 vs.20.12, P = 0.003) and day 21 (22.39 vs. 20.43, P = 0.001). No apparent differences were found in anxiety and depression assessment between these groups. Participants in both groups were well tolerant of acupuncture therapy. There was no adverse event occurs in our study.ConclusionAcupuncture as an adjunctive approach could alleviate the severity of chemotherapy-induced nausea and vomiting compared to the sham control, even though the effect of acupuncture in preventing CINV occurring is relatively modest.