scholarly journals Neuropathy severity at the time of oxaliplatin treatment alteration in patients with colon cancer (Alliance A151912).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12090-12090
Author(s):  
Daniel Louis Hertz ◽  
Travis Dockter ◽  
Daniel V. Satele ◽  
Charles L. Loprinzi ◽  
Jennifer Le-Rademacher
Keyword(s):  
Colon Cancer ◽  
Peripheral Neuropathy ◽  
Dose Reduction ◽  
Oxaliplatin Treatment ◽  
End Of Treatment ◽  
Chi Squared ◽  
Few Data ◽  
Eortc Qlq ◽  
To Receive ◽  
Clinical Trial Information

12090 Background: Clinical guidelines recommend altering chemotherapy treatment by decreasing, delaying, or discontinuing dosing in patients (pts) experiencing chemotherapy-induced peripheral neuropathy (CIPN). There are few data available on clinical use of treatment alteration including the severity of CIPN at the time of alteration. Our objective was to investigate the incidence of oxaliplatin treatment alterations and CIPN severity at that time. Methods: This was a retrospective analysis of pts with colon cancer scheduled to receive oxaliplatin-containing combination chemotherapy on the N08CB trial of intravenous calcium and magnesium for prevention of CIPN. Dose alterations were not mandated by the N08CB protocol. Clinicians assessed CIPN using NCI-CTCAE V.4.0; pts used the sensory subscale of the EORTC-QLQ Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN8). Pts were classified as 1) completed oxaliplatin treatment without alteration, 2) dose reduction or delay due to CIPN, 3) discontinuation due to CIPN, 4) discontinuation due to other AE, or 5) discontinuation for another reason. Comparisons focused primarily on pts with alteration due to CIPN (groups 2 and/or 3) compared with pts completing treatment without alteration (group 1) using chi-squared and Kruskal-Wallis tests. Results: In this analysis of 350 N08CB pts, 135 (39%) completed oxaliplatin without treatment alteration, 70 (20%) had a dose reduction (n=66) or delay (n=4) due to CIPN and 35 (10%) discontinued early due to CIPN. Pts who experienced alterations due to CIPN were younger (p=0.0249) and more likely to be female (p=0.008). Clinician-assessed CIPN severity was greater in pts at the time of dose reduction or delay compared with CIPN severity at the end of treatment in pts with no alteration (p<0.0001). Pt-assessed CIPN severity was not different in pts who completed treatment without alteration compared to pts who had a dose reduction or delay (p=0.88) or a discontinuation (p=0.37). CIPN8 scores at cycle 4 were higher (worse) in pts who eventually had any alteration (i.e., reduction, delay, or discontinuation) compared to pts who completed treatment without any alteration (median CIPN8 11.5 vs. 7.7, p=0.023). Conclusions: Treatment alterations due to CIPN are relatively common in pts receiving adjuvant oxaliplatin for colon cancer and are associated with clinician-assessed but not pt-reported CIPN severity. Rapid CIPN8 increases early in treatment are indicative of increased likelihood of a future oxaliplatin treatment alteration, indicating a potential use of early monitoring and intervention. Support: UG1CA189823; https://acknowledgments.alliancefound.org. Clinical trial information: NCT01099449 (NCCTG N08CB).

scholarly journals Neuropathy Severity at the Time of Oxaliplatin Treatment Alteration in Patients with Colon Cancer (Alliance A151912)

2021 ◽  
Author(s):  
Daniel Hertz ◽  
Travis J Dockter ◽  
Daniel V Satele ◽  
Charles L Loprinzi ◽  
Jennifer G Le-Rademacher
Keyword(s):  
Colon Cancer ◽  
Peripheral Neuropathy ◽  
Dose Reduction ◽  
Clinical Use ◽  
Chemotherapy Treatment ◽  
Oxaliplatin Treatment ◽  
End Of Treatment ◽  
Patient Reported ◽  
Few Data ◽  
Group 1

Abstract Background: Clinical guidelines recommend altering chemotherapy treatment by decreasing, delaying, or discontinuing dosing in patients who are experiencing chemotherapy-induced peripheral neuropathy. There are few data available on the clinical use of treatment alteration including the severity of CIPN at the time of treatment alteration. Methods: This was a retrospective analysis of patients receiving oxaliplatin on the NCCTG N08CB trial. Neuropathy severity was assessed at each cycle by clinicians and patients. Patients were classified as 1) completed treatment without alteration, 2) dose reduction or delay due to neuropathy, 3) discontinuation due to neuropathy, or discontinuation for other toxicity (4), or another reason (5). Comparisons focused primarily on patients with alteration due to neuropathy (groups 2 and/or 3) compared with patients who completed treatment without alteration (group 1). Results: In 350 participants, 135 (39%) completed treatment without alteration, 70 (20%) had a dose reduction or delay due to neuropathy, and 35 (10%) discontinued early due to neuropathy. Clinician-assessed neuropathy severity was greater in patients at the time of dose reduction or delay compared with severity at the end of treatment in patients without alteration (p<0.0001). Patient-reported neuropathy severity at cycle 4 was worse in patients who had an alteration as compared with patients who completed treatment without alteration (p=0.017). Conclusions: Treatment alterations due to neuropathy are common in patients receiving oxaliplatin for colon cancer and are associated with clinician-assessed neuropathy severity. Rapid increases in patient-reported neuropathy severity indicate a potential need for monitoring and intervention.

Potential use of Pain Vision as an objective method to evaluate chemotherapy-induced peripheral neuropathy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20557-e20557 ◽  
Author(s):  
Yuko Tanabe ◽  
Chikako Shimizu ◽  
Akihiro Hirakawa ◽  
Eriko Nara ◽  
Emi Noguchi ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Post Treatment ◽  
Objective Method ◽  
Questionnaire Item ◽  
Evaluation Point ◽  
Treatment Comparisons ◽  
To Receive ◽  
Potential Use ◽  
Reproducible Manner ◽  
Clinical Trial Information

e20557 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse event, but no objective method exists to evaluate CIPN in an easy-to-use and reproducible manner. Pain Vision (PS-2100; Nipro Co., Osaka, Japan) (PV) was developed to quantitatively evaluate peripheral neuropathy using minimum threshold electric current (mTEC) by painless stimulus. PV has been reported useful in evaluating diabetic neuropathy and neuropathic pain induced by other causes. We investigated the usefulness of PV as an objective method to evaluate CIPN. Methods: Breast and ovarian cancer patients, who were intended to receive adjuvant chemotherapy including paclitaxel (PTX), were enrolled in a clinical study to explore SNPs related to CIPN (UMIN000005294). CIPN was prospectively evaluated at baseline, mid-treatment after receiving a total PTX dosage of 480mg/m2 and three weeks following treatment completion using NCI-CTC (v4), FACT-Neurotaxane (FACT-Ntx) and mTEC as measured by PV. Correlations between changes of mTEC readings and NCI-CTC or FACT-Ntx were analyzed using generalized estimating equations. Results: Ninety-four women were enrolled in this study between April 2011 and December 2012, 15 patients had not reached the post-treatment evaluation point at time of this analysis. Median age was 50 years (range, 27-78) and the incidence of CIPN was 99%. No patient had CIPN at baseline. Mid-treatment and post-treatment CIPN grades were 0/1/2/3=9/70/15/0 and 3/41/30/5 using NCI-CTC while median mTEC readings at baseline, mid-treatment and post-treatment points were 7.8 (4.9-19.9), 8.6 (5.1-17.8) and 9.7 (5.3-22.4)μA, respectively. In baseline and post-treatment comparisons, median mTEC reading changes were significantly correlated with every NCI-CTC grade (median mTEC changes for grades 1/2/3=0.39/0.36/0.64; p=0.003/0.019/0.004) and FACT-Ntx questionnaire item nine, “I have trouble feeling the shape of small objects when they are in my hand” (median mTEC change of 0.14; p=0.049). Conclusions: PV may be potentially useful as an objective method to evaluate CIPN, in particular sensory dominant CIPN, but further study is necessary. Clinical trial information: 000005294.

Splenomegaly during oxaliplatin-based chemotherapy in colon cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 88-88
Author(s):  
Ruoyu Ji ◽  
Guanghua Huang ◽  
Lingshan Liu ◽  
Mengyin Chen ◽  
Xiaoduo Yu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dose Reduction ◽  
Dose Intensity ◽  
Cancer Center ◽  
Computed Tomographic ◽  
Oxaliplatin Treatment ◽  
Splenic Enlargement ◽  
Primary Colon Cancer ◽  
Primary Colon ◽  
Splenic Size

88 Background: Splenic enlargement has been reported in patients treated with oxaliplatin. However, the characteristics of oxaliplatin-induced splenomegaly were not well studied. Here we evaluated the change of splenic volume and its clinical significance in patients treated by oxaliplatin-based regimen. Methods: Patients with stage II-IV primary colon cancer treated with oxaliplatin and capecitabine in China National Cancer Center from January 2016 to December 2017 were screened for this retrospective study. Those with complete laboratory tests and computed tomographic data before, during and up to 1.5 years after the chemotherapy were selected. The splenic size was measured by AWVolumeshare5. Splenomegaly was defined as an over 30% increase of splenic size from baseline. Recovery of splenomegaly was defined as the splenic size fell back to a 0.9 to1.1-fold range of baseline. Results: Out of a total of 144 patients, 102 (70.8%) had over 30% increase, 72 (50.0%) had over 50% increase, and 22 (15.3%) had over 100% increase in splenic size after oxaliplatin-based regimen. Among the 102 splenomegaly patients, 5 (4.9%) develop splenomegaly within 3 chemotherapy cycles, 53 (53.0%) within 6 cycles, 73 (71.6%) within 9 cycles, and 102 (100.0%) within 3 months after the last administration of oxaliplatin. Compared to the group without splenomegaly, patients with splenomegaly received more cycles of oxaliplatin administrations (median 8 vs 6, p < 0.001) and greater dose intensity (total dose per square meter) (median 822.8mg/m2 vs 629.3mg/m2, p < 0.001). Patients with splenomegaly had higher incidence of thrombocytopenia (61.7% vs 38.1%, p = 0.009) and are more likely to undergo oxaliplatin dose reduction due to thrombocytopenia (21.6% vs 7.1%, p = 0.038). The recovery rates of splenic size within 0.5, 1 and 1.5 years after the end of oxaliplatin treatment were 23.2%, 50.6% and 74.3%, respectively. Conclusions: Splenomegaly are common in patients treated with oxaliplatin-based chemotherapy, and most would recover in 1.5 years after completion of therapy. Patients with splenomegaly are prone to experience thrombocytopenia and oxaliplatin dose reduction. Further studies are needed to reveal the mechanism how oxaliplatin induce splenomegaly.

scholarly journals Vitamin E for prevention of oxaliplatin-induced peripheral neuropathy: a pilot randomized clinical trial

2013 ◽  
Vol 131 (1) ◽  
pp. 35-38 ◽  
Author(s):  
Samuel Oliveira de Afonseca ◽  
Felipe Melo Cruz ◽  
Daniel de Iracema Gomes Cubero ◽  
Andrea Thaumaturgo Lera ◽  
Fernanda Schindler ◽  
...  
Keyword(s):  
Placebo Group ◽  
Vitamin E ◽  
Peripheral Neuropathy ◽  
Group Versus ◽  
University Hospital ◽  
Magnesium Supplementation ◽  
Oxaliplatin Treatment ◽  
Before And After ◽  
The Common ◽  
To Receive

CONTEXT AND OBJECTIVEOxaliplatin is one of the chemotherapy regimens most used for treating colorectal cancer. One of the main limitations to its use is induction of peripheral neuropathy. Previous studies have shown that vitamin E can reduce the incidence of peripheral neuropathy by 50%. This study aimed to assess the effectiveness of vitamin E for prevention of oxaliplatin-induced peripheral neuropathy.DESIGN AND SETTINGProspective, phase II, randomized pilot study developed at a university hospital in the Greater ABC region.METHODSPatients were randomized five days before starting oxaliplatin treatment, to receive either vitamin E or placebo until the end of the chemotherapy regimen. The outcome was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 3, and specific gradation scales for oxaliplatin-induced peripheral neuropathy. Patients with colorectal and gastric cancer who had been scheduled to receive oxaliplatin-based chemotherapy were included. Both groups received calcium and magnesium supplementation before and after oxaliplatin infusions.RESULTSEighteen patients were randomized to the vitamin E group and 16 to the placebo group. Cumulative incidence of 83% with peripheral neuropathy grades 1/2 was observed in the vitamin E group, versus 68% in the placebo group (P = 0.45). A trend towards more diarrhea was observed among patients who received vitamin E (55.6% vs. 18.8%; P = 0.06). There were no other significant differences in toxicity between the groups.CONCLUSIONSNo significant decrease in the incidence of acute oxaliplatin-induced peripheral neuropathy was demonstrated through vitamin E use.CLINICAL TRIAL REGISTRATIONNCT01523574.

Clinical course of patients with cisplatin (CDDP)-associated neuropathy compared to other neurotoxic chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23078-e23078 ◽  
Author(s):  
Costantine Albany ◽  
Travis Dockter ◽  
Eric G Wolfe ◽  
Deirdre R. Pachman ◽  
Nina D. Wagner-Johnston ◽  
...  
Keyword(s):  
Clinical Course ◽  
Sensory Neuropathy ◽  
Outcome Data ◽  
Individual Item ◽  
Burning Pain ◽  
Scoring Algorithm ◽  
Eortc Qlq ◽  
To Receive ◽  
Clinical Trial Information ◽  
Better Than

e23078 Background: There are limited patient (pt) reported outcome data regarding CDDP neurotoxicity. Methods: CDDP-induced peripheral neuropathy was evaluated in pts with testicular cancer planning to receive CDDP (20 mg/m2/d for 5 days) for ≥ 3 cycles. Neurotoxicity was assessed with the EORTC QLQ-CIPN20 tool before each CDDP cycle and every 2-4 months after, out to 18 months. We compared these data to our studies evaluating pts receiving doxorubicin/cyclophosphamide (AC), paclitaxel and oxaliplatin. The total score of the EORTC QLQ-CIPN20, each of the three subscale scores and each individual item was computed following the standard scoring algorithm and converted to a 0-100 scale. Descriptive statistics and graphical plots were utilized. Results: 54 pts receiving CDDP (mean age 33 years) and 18 pts receiving AC were evaluated. Following completion of CDDP, neuropathy symptoms (sensory neuropathy score and numbness/tingling in toes/feet) worsened for about 6 months (consistent with the so-called “coasting phenomena”), similar to what had previously been seen with oxaliplatin (but different than what had been seen with paclitaxel). For CDDP pts, during therapy, numbness and tingling in fingers/hands were more prominent, than the same symptoms in the toes/feet. After therapy was completed, numbness, and tingling became more prominent in toes/feet, but improved in the fingers/hands. After stopping therapy, shooting/burning pain did not worsen in upper or lower extremities. During therapy, CDDP pts had less problems than had previously been seen with oxaliplatin or paclitaxel, maybe because of the younger ages of the CDDP pts. With AC, all of the CIPN-20 sensory neuropathy scores were better than was seen in the pts receiving CDDP and also in pts receiving paclitaxel and oxaliplatin in previous evaluations. Conclusions: CDDP-induced neuropathy is more similar to oxaliplatin-induced neuropathy than paclitaxel-induced neuropathy. AC chemotherapy pts do not have substantial changes in CIPN 20 scores, consistent with the CIPN 20 instrument being a measure of chemotherapy-induced neuropathy, as opposed to more general chemotherapy-induced toxicities. Clinical trial information: NCT02677727.

scholarly journals The course of peripheral neuropathy and its association with health-related quality of life among colorectal cancer patients

2020 ◽  
Author(s):  
Cynthia S. Bonhof ◽  
Lonneke V. van de Poll-Franse ◽  
Dareczka K. Wasowicz ◽  
Laurens V. Beerepoot ◽  
Gerard Vreugdenhil ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Peripheral Neuropathy ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related ◽  
Eortc Qlq ◽  
The Impact

Abstract Purpose To gain more insight into the course of chemotherapy-induced peripheral neuropathy (CIPN) and its impact on health-related quality of life (HRQoL) in a population-based sample of colorectal cancer (CRC) patients up to 2 years after diagnosis. Methods All newly diagnosed CRC patients from four hospitals in the Netherlands were eligible for participation in an ongoing prospective cohort study. Patients (n = 340) completed questions on CIPN (EORTC QLQ-CIPN20) and HRQoL (EORTC QLQ-C30) before initial treatment (baseline) and 1 and 2 years after diagnosis. Results Among chemotherapy-treated patients (n = 105), a high sensory peripheral neuropathy (SPN) level was reported by 57% of patients at 1 year, and 47% at 2-year follow-up, whereas a high motor peripheral neuropathy (MPN) level was reported by 47% and 28%, at years 1 and 2, respectively. Linear mixed model analyses showed that SPN and MPN symptoms significantly increased from baseline to 1-year follow-up and did not return to baseline level after 2 years. Patients with a high SPN or MPN level reported a worse global quality of life and a worse physical, role, emotional, cognitive, and social functioning compared with those with a low SPN or MPN level. Conclusions Future studies should focus on understanding the mechanisms underlying CIPN so targeted interventions can be developed to reduce the impact of CIPN on patient’s lives. Implications for cancer survivors Patients need to be informed of both CIPN and the impact on HRQoL.

VP39 The Alphabet Lottery? How NICE Outcomes Vary By Appraisal Committee

2019 ◽  
Vol 35 (S1) ◽  
pp. 86-86
Author(s):  
Richard Macaulay ◽  
Lok Wan Liu ◽  
Cornelia Roibu ◽  
Andrea Berardi
Keyword(s):  
Cost Effectiveness ◽  
The Other ◽  
Appraisal Committee ◽  
Technology Appraisal ◽  
The Public ◽  
Chi Squared ◽  
C 50 ◽  
To Receive ◽  
Disciplinary Group ◽  
53 C 55

IntroductionNICE (National Institute for Health and Care Excellence) makes recommendations on the public reimbursement of medicines based on their clinical- and cost-effectiveness. The recommendation is made by an Appraisal Committee (comprising a multi-disciplinary group of independent experts) as part of a technology appraisal. There are four Appraisal Committees (A,B,C,D); this research investigates whether appraisal outcomes vary by committee.MethodsAll publicly-available Final Appraisal Determinations from NICE Single Technology Appraisals (STA) were screened (01/10/2009-14/11/2018) and key data were extracted. Homogeneity in rates of acceptance or rejection across the committees was assessed using Chi-squared tests.ResultsThe Appraisal Committee was identified for 298 technologies, 56% (168/298) of which were ‘recommended’. The number of technologies assessed by each committee was similar (A:79, B:62, C:91, D:66). However, STAs conducted by Committee D were significantly less likely to receive ‘recommended’ outcomes (A:68% [54/79], B:65% [40/62], C:53% [48/91], D:39% [26/66]; p < 0.01). STAs for oncology indications had higher ’not recommended’ outcomes than those for non-oncology indications (25% vs. 9%). The lower ‘recommendation’ rates for committee D persisted across oncology (A:60%, B:83%, C:50%, D:38%; p = 0.01) and non-oncology indications (A:73%, B:53%, C:55%, D:40%; p < 0.01). However, STAs conducted by Committee D were significantly more likely to receive ‘optimized’ recommendations (A:16%, B:21%, C:33%, D: 36%; p < 0.01) and when considering the rates of ‘recommended’ and ‘optimized’ outcomes compared to ‘only in research’ and ‘not recommended’ outcomes, no significant differences were found (A:85%, B: 85%, C:86%, D:76%; p = 0.27).ConclusionsSTAs undertaken by NICE Appraisal Committee D was associated with a significantly lower rate of ‘recommended’ outcomes but tended to an ‘optimized’ recommendation significantly more than the other committees. Further research is needed to determine if this reflects any deviation in uniform implementation of NICE methodology between Committees.

scholarly journals Gametocyte carriage after seasonal malaria chemoprevention in Plasmodium falciparum infected asymptomatic children

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Abdullahi Ahmad ◽  
Aurelia Prom ◽  
John Bradley ◽  
Mamadou Ndiath ◽  
Blessed Etoketim ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Comparison Group ◽  
Conditional Logistic Regression ◽  
Gametocyte Carriage ◽  
Asymptomatic Children ◽  
Seasonal Malaria Chemoprevention ◽  
Before And After ◽  
Chi Squared ◽  
Comparison Groups ◽  
To Receive

Abstract Background Treatment of clinical Plasmodium falciparum malaria with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) is associated with increased post-treatment gametocyte carriage. The effect of seasonal malaria chemoprevention (SMC) with SP and AQ on gametocyte carriage was assessed in asymptomatic P. falciparum infected children. Methods The study was carried out in eastern Gambia. Asymptomatic P. falciparum malaria infected children aged 24–59 months old who were eligible to receive SMC (SMC group) and children 5–8 years that were not eligible to receive SMC (comparison group) were recruited. Gametocytaemia was determined by molecular methods before and after SMC administration. Gametocyte carriage between the groups was compared using the chi-squared test and within-person using conditional logistic regression. Results During the 2017 and 2018 malaria transmission seasons, 65 and 75 children were recruited in the SMC and comparison groups, respectively. Before SMC administration, gametocyte prevalence was 10.7% (7/65) in the SMC group and 13.3% (10/75) in the comparison group (p = 0.64). At day 13 (IQR 12, 13) after SMC administration, this was 9.4% (5/53) in children who received at least the first dose of SMC treatment and 12.7% (9/71) for those in the comparison group (p = 0.57). Similarly, there was no difference in prevalence of gametocytes between children that adhered to all 3-day doses of SMC treatment 15.6% (5/32) and those in the comparison group (p = 0.68). In the SMC group, within-group gametocyte carriage was similar before and after SMC administration in children that received at least the first dose of SMC treatment (OR 0.6, 95% CI 0.14–2.51; p = 0.48) and in those that adhered to all 3-day doses of SMC treatment (OR 1.0, 95% CI 0.20–4.95; p = 1.0). Conclusion In this study with relative low gametocyte prevalence prior to SMC treatment, no evidence was observed that SMC treatment increased gametocyte carriage in asymptomatic P. falciparum malaria infected children.

Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced non-clear cell renal cell carcinoma (nccRCC) (HCRN GU16-260-Cohort B).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4510-4510
Author(s):  
Michael B. Atkins ◽  
Opeyemi Jegede ◽  
Naomi B. Haas ◽  
David F. McDermott ◽  
Mehmet Asim Bilen ◽  
...  
Keyword(s):  
Clear Cell ◽  
Metastatic Lesion ◽  
Limited Information ◽  
Cell Renal Cell Carcinoma ◽  
Best Response ◽  
Treatment Naïve ◽  
Correlative Studies ◽  
Grade 3 ◽  
To Receive ◽  
Clinical Trial Information

4510 Background: The HCRN GU16-260 trial reported on the efficacy and toxicity of nivo monotherapy in treatment naïve clear cell RCC (Cohort A) and the efficacy of nivo/ipi salvage therapy in pts with tumors resistant to initial nivo monotherapy (Atkins JCO 2020.38.15_suppl.5006). Limited information is available on the effects of such an approach in pts with advanced nccRCC. Methods: Eligible pts with treatment-naïve nccRCC received nivo 240mg IV q2 wk x 6 doses followed by 360mg IV q3 wk x 4 doses followed by 480 mg q4 wk until progressive disease (PD), toxicity, or completion of 96 wks of treatment (Part A). Pts with PD prior to or stable disease (SD) at 48 wks (pSD) were potentially eligible to receive salvage nivo (3mg/kg) /ipi (1 mg/kg) q3 wk x 4 doses followed by q4 wk nivo maintenance for up to 48 wks (Part B). All pts were required to submit tissue from a metastatic lesion obtained within 12 months (mo) prior to study entry and prior to enrolling on Part B for correlative studies. Results: 35 pts with nccRCC were enrolled between 5/2017 and 12/2019 at 12 participating HCRN sites. Median age 63 (range 35-84 years); 89% male. IMDC favorable 8 (23%), intermediate 18 (51%) and poor risk 9 (26%). Of the 35 pts 19 (54%) had papillary, 6 (17%) chromophobe and 10 (29%) unclassified histology. RECIST defined ORR was 5 of 35 (14.3%) [CR 2 (5.7%), PR 3 (8.6%)], SD 16 (45.7%), PD 14 (40.0%). Immune-related ORR was 8 of 35 (22.9%). RECIST ORR by histology was: papillary - 1/19 (5%); chromophobe - 1/6 (17%); unclassified - 3/10 (30%). 9 pts (26%) had tumors with sarcomatoid features with 3 (33%) (2 unclassified, 1 papillary) responding. Median PFS was 4.0 (2.7, 4.3) mo. 21 pts remain alive. None of the responders have progressed or died. 28 pts (25 PD, 3 pSD) were potentially eligible for salvage nivo/ipi (Part B), but 12 did not enroll due to symptomatic PD (2), grade 3-4 toxicity on nivo (3), or other including no biopsy tissue (7). In the 16 Part B pts, best response to nivo/ipi was: PR (1, 6%) – (unclassified/non-sarcomatoid); SD (7, 44%); PD (8, 50%). Grade 3 Treatment-related adverse events (TrAEs) were seen in 7/35 (20%) on nivo. Grade 3-5 TrAEs were seen in 7/16 (44%) on nivo/ipi with 1 pt experiencing sudden death. Correlative studies including PD-L1 status, WES and RNAseq are pending. Conclusions: Nivo monotherapy has limited activity in treatment naïve nccRCC with most responses (4 of 5) seen in pts with sarcomatoid and/or unclassified tumors. Toxicity is consistent with prior nivo studies. Salvage treatment with nivo/ipi was provided in 16 of 28 (57%) pts with PD/pSD on nivo monotherapy, with 1 response observed. Clinical trial information: NCT03117309.

Nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced non-small cell lung cancer (NSCLC): 4-year update from CheckMate 227.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9016-9016
Author(s):  
Luis G. Paz-Ares ◽  
Tudor-Eliade Ciuleanu ◽  
Jong-Seok Lee ◽  
Laszlo Urban ◽  
Reyes Bernabe Caro ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Programmed Death ◽  
Long Term Follow Up ◽  
To Receive ◽  
Clinical Trial Information

9016 Background: 1L NIVO + IPI was shown to provide durable long-term overall survival (OS) benefit vs chemo regardless of tumor programmed death ligand 1 (PD-L1) expression in patients (pts) with advanced NSCLC in CheckMate 227 Part 1 (NCT02477826); 3-year OS rates were 33% vs 22% in pts with PD-L1 ≥ 1% (HR, 0.79 [95% CI, 0.67–0.93]) and 34% vs 15% in pts with PD-L1 < 1% (HR, 0.64 [95% CI, 0.51–0.81]). Here we report updated results from the study with 4 years’ minimum follow-up. Methods: Adults with previously untreated stage IV / recurrent NSCLC, no known EGFR/ ALK alterations , and ECOG performance status ≤ 1 were enrolled; pts were stratified by squamous (SQ) and non-squamous (NSQ) histology. Pts with PD-L1 ≥ 1% (n = 1189) were randomized 1:1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO alone (240 mg Q2W), or chemo. Pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to receive NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. OS with NIVO + IPI vs chemo in pts with PD-L1 ≥ 1% was the primary endpoint. Results: With minimum follow-up of 49.4 months (database lock, Feb 18, 2021), pts were at least 2 years beyond the protocol-specified end of immunotherapy treatment. Pts with PD-L1 ≥ 1% continued to show durable benefit with NIVO + IPI vs chemo (HR, 0.76 [95% CI, 0.65–0.90]); 4-year OS rates were 29% (NIVO + IPI), 21% (NIVO), and 18% (chemo). At 4 years, 14% (NIVO + IPI), 10% (NIVO), and 4% (chemo) remained progression free. Among responders, 34%, 30%, and 7% remained in response, respectively. In an exploratory analysis in pts with PD-L1 ≥ 50%, 4-year OS rates were 37% (NIVO + IPI), 26% (NIVO), and 20% (chemo). In pts with PD-L1 < 1%, OS HR for NIVO + IPI vs chemo was 0.64 (95% CI, 0.51–0.81); 4-year OS rates were 24% (NIVO + IPI), 13% (NIVO + chemo) and 10% (chemo). At 4 years, 12% (NIVO + IPI), 7% (NIVO + chemo), and 0% (chemo) remained progression free. Among responders, 31%, 13%, and 0% remained in response, respectively. Among pts who progressed on NIVO + IPI vs chemo, 7% vs 40% (PD-L1 ≥ 1%), and 9% vs 33% (PD-L1 < 1%), received subsequent immunotherapy. Benefit with NIVO + IPI vs chemo was observed for both SQ and NSQ histology (Table). With long-term follow-up, no new safety signals were identified. Conclusions: With 4 years’ minimum follow-up, 1L NIVO + IPI continued to provide durable, long-term OS benefit vs chemo in pts with advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826. [Table: see text]

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