Non-Platinum-Containing Combination Chemotherapy for Stage III-IV Head and Neck Squamous Carcinoma

1983 ◽  
Vol 69 (4) ◽  
pp. 323-326
Author(s):  
Andrea Veronesi ◽  
M. Donatella Magri ◽  
Umberto Tirelli ◽  
Enzo Galligioni ◽  
Sergio Frustaci ◽  
...  
Keyword(s):  
Head And Neck ◽  
Mitomycin C ◽  
Combination Chemotherapy ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Squamous Carcinoma ◽  
Good Patient ◽  
Good Patient Compliance

From May 1980 to November 1981, 51 consecutive patients with locally advanced, recurrent or metastatic head and neck squamous carcinoma were treated with 2 successive outpatient chemotherapeutic regimens including adriamycin, cyclophosphamide, vincristine, bleomycin, methotrexate and 5-fluorouracil with or without mitomycin-C. A 34% objective response rate was obtained with acceptable toxicity and good patient compliance. The presence of mitomycin-C did not influence response rate. Median survival was 9 months.

Chemotherapy of Advanced Head and Neck Squamous Carcinoma with Cisplatin, Fluorouracil and Bleomycin Administered in an Outpatient Schedule

1988 ◽  
Vol 74 (5) ◽  
pp. 559-562
Author(s):  
Andrea Veronesi ◽  
Maria Donatella Magri ◽  
Silva Foladore ◽  
Ettore Bidoli ◽  
Roberto Innocente ◽  
...  
Keyword(s):  
Complete Remission ◽  
Head And Neck ◽  
Response Rate ◽  
Locally Advanced ◽  
Squamous Carcinoma ◽  
Advanced Head ◽  
Accurate Assessment ◽  
Risk Patients ◽  
Previously Treated ◽  
Good Risk

From May 1983 to September 1984, 48 consecutive patients with locally advanced, recurrent and/or metastatic head and neck squamous carcinoma were treated with cisplatin 60 mg/m2 i.v. on day 1, fluorouracil 10 mg/kg i.v. push from day 1 to day 4 and bleomycin 10 mg/m2 i.v. from day 1 to day 4, every 3 weeks. In the 44 evaluable patients complete remission was observed in 4, partial remission in 9, stable disease in 19, and progression in 12, for a 29.5% response rate. When the analysis was limited to the 21 patients with PS > 70 and no previous chemotherapy or radiotherapy, the response rate was 48%. Toxicity was acceptable, and no treatment related deaths occurred. Overall median survival (all eligible patients) was 7 months. Although further studies with this combination in poor risk patients (previously treated or with PS < 70) do not appear to be indicated, a more accurate assessment in good risk patients might be warranted.

Combined analysis of two phase II trials of imatinib in advanced dermatofibrosarcoma protuberans (DFSP)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10520-10520 ◽  
Author(s):  
S. Schuetze ◽  
P. Rutkowski ◽  
M. M. Van Glabbeke ◽  
C. Rankin ◽  
B. P. Rubin ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Chromosome 17 ◽  
Low Grade ◽  
Time To Progression ◽  
Phase Ii Trials ◽  
Two Phase

10520 Background: DFSP is an infiltrative, low-grade, dermal tumor with propensity to recur locally and occasionally metastasize. Translocation between COL1A1 on chromosome 17 and PDGFB on chromosome 22, which results in transcriptional upregulation of PDGFB, is characteristic of DFSP. Autocrine/paracrine PDGFB-mediated activation of PDGFRB drives DFSP proliferation. Two distinct phase II trials of imatinib in patients (pts) with locally advanced or metastatic DFSP were conducted, 1 in North America (SWOG) with confirmed objective response rate and 1 in Europe (EORTC) with 14 week progression-free rate as primary end-points. Methods: Pts with locally advanced or metastatic DFSP were eligible. In the EORTC trial confirmation of t(17;22) by FISH was prospectively required for participation, imatinib was started at 400mg bid, surgery was undertaken after 14 weeks if feasible and response was assessed at 14 weeks. Full accrual was to be 44 pts in one step. In the SWOG trial confirmation of t(17;22) by RT-PCR was performed after enrollment, imatinib was started at 400mg daily and response was assessed every 8 weeks. Full accrual was to be 40 pts in 2 steps. Results: 16 pts were enrolled in EORTC and 8 pts enrolled in SWOG trial. The studies were closed early because of slow accrual and regulatory approval of imatinib in DFSP. Pts age ranged from 24 to 70 yrs, DFSP was located on head/neck, trunk and extremity in 7, 11 and 6 pts, respectively, ranged in size from 1.2–49 cm and was classic, pigmented and fibrosarcomatous DFSP in 13, 1 and 7 pts, respectively. One patient did not have DFSP on central review, lacked t(17;22) and thus was ineligible. Metastases were present in 7 pts involving lung in 6 pts. 11 pts (46%) had partial response, 9 pts had stable disease and 4 pts had progressive disease as best response. Median time to progression was 1.7 yrs. Response and progression-free at 1 yr rates were similar between studies. Imatinib was stopped in 11 pts for progression, 1 pt for toxicity, 2 pts resected free of gross disease and 1 pt withdrew. Conclusions: Imatinib is active in DFSP harboring t(17;22) with an objective response rate approaching 50% and is active in fibrosarcomatous DFSP. Response rates and time to progression did not appear to differ between pts taking 400 mg daily versus 400 mg bid. [Table: see text]

Combined modality therapy with radiation therapy (RT), chemotherapy, bevacizumab, and erlotinib in the treatment of patients (pts) with locally advanced squamous carcinoma of the head and neck

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6012-6012 ◽  
Author(s):  
A. A. Meluch ◽  
D. Spigel ◽  
H. A. Burris ◽  
C. Lane ◽  
J. D. Peyton ◽  
...  
Keyword(s):  
Head And Neck ◽  
Induction Therapy ◽  
Combined Modality Therapy ◽  
Objective Response ◽  
Locally Advanced ◽  
Squamous Carcinoma ◽  
Concurrent Chemotherapy ◽  
Advanced Head ◽  
Combined Modality ◽  
Grade 3

6012 Background: Concurrent chemotherapy/RT is the standard of treatment for locally advanced head and neck cancer. Agents targeting EGFR and the angiogenesis pathway have also demonstrated activity. In this phase II trial, we added bevacizumab and erlotinib to an active combined modality regimen in the first-line treatment of pts with locally advanced head and neck cancer. Methods: Eligible pts had previously untreated squamous carcinoma of any head and neck site, with T3/T4 primary lesions and/or N1-N3 nodal involvement. Additional eligibility: ECOG PS 0 or 1; adequate organ function; indwelling central venous catheter; standard bevacizumab exclusions. All pts received induction therapy with 2 courses of paclitaxel (200mg/m2), carboplatin (AUC 6.0), 5-FU (200mg/m2 per day, 24 hour CI days 1–21), and bevacizumab (15 mg/kg); cycles were repeated at 21-day intervals. Pts then received concurrent RT (68.4 Gy, 1.8 Gy/day), paclitaxel (50 mg/m2 weekly x 6), bevacizumab (15 mg/kg weeks 1 and 4), and erlotinib (150 mg daily x 7 weeks). PFS was the primary endpoint. Results: Between December 2006 and July 2008, 60 pts were enrolled; the first 48 pts are included in this preliminary report. The median age was 56 years; T3/T4 = 9/8; N1/N2/N3 = 13/27/4. 45 pts (94%) completed the 6-week induction therapy, and 41 pts (85%) completed all therapy. After induction therapy, 56% of pts had objective response; 77% had objective response after completion of therapy. After a median follow-up of 16 months, the 18-month progression-free and overall survivals are 85% and 87%, respectively. Grade 3/4 toxicity during induction therapy included neutropenia (46%), neutropenic fever (6%), mucositis (14%), diarrhea (14%), and hand/foot syndrome (11%). Severe local toxicity (mucositis/esophagitis) occurred in 31 patients (76%) during combined modality therapy (56% grade 3/20% grade 4). Conclusions: The addition of bevacizumab and erlotinib to concurrent chemotherapy/RT was feasible, with no unexpected toxicity. After short followup, the regimen appears highly active. Updated results will be presented. [Table: see text]

A phase II study of RC48-ADC in HER2-positive patients with locally advanced or metastatic urothelial carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4509-4509 ◽  
Author(s):  
Xinan Sheng ◽  
Ai-Ping Zhou ◽  
Xin Yao ◽  
Yanxia Shi ◽  
Hong Luo ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Locally Advanced ◽  
Visceral Metastasis ◽  
Her2 Positive ◽  
Metastatic Urothelial Carcinoma

4509 Background: Urothelial carcinoma (UC) is the third largest cancer type with HER2 positive cancer. RC48-ADC is a novel humanized anti-HER2 antibody-drug conjugate (ADC). This study was to evaluate the activity of RC48-ADC in HER2-positive patients with locally advanced or metastatic urothelial carcinoma (mUC). Methods: This study is an open-label, multicenter, single-arm, non-randomized phase II study. Eligibility criteria include: histologically confirmed UC, HER2-positive (IHC 2+ or 3+), ECOG PS 0-1, treated with ≥1 prior systemic treatment. The patients received RC48-ADC treatment alone (2 mg/kg IV infusion, q2w) until disease progression, unacceptable toxicity, withdrawal, or study termination. The primary endpoint was objective response rate (ORR). Progress-free survival (PFS), overall survival (OS), and safety was also assessed. Results: Patient enrollment for this study was completed in November 2018. A total of 43 patients were enrolled, with a median age of 64 years old. At baseline, most patients (37/43) had visceral metastasis. Fourteen (32.6%) patients had received ≥ 2 lines treatment and 8 (18.6%) patients had prior immune checkpoint inhibitor (CPI) therapy in second line treatment. The objective response rate was 60.5% (95% CI: 44.4%, 75.0%) and the DCR was 90.7% (39/43). As of Jan 23, 2019, the median PFS for the overall study population was not yet reached, and the median PFS was 7.8 months (95% CI: 4.9, 10.7) for the 9 patients who started RC48-ADC prior to Jun 30, 2018. The ORR was 70.6% (12/17) in patients with HER2 FISH+ or IHC3+. The ORR was 64.9% (24/37) in patients with visceral metastasis and was 70.0% (14/20) in liver metastasis patients especially. The ORR was 64.3% in patients post to ≥ 2 lines treatment and 75.0% in patients post to immunotherapy. Common treatment-related AEs were leukopenia (51.2%), hypoesthesia (41.9%), alopecia (41.9%), neutropenia (37.2%), fatigue (34.9%), ALT increase (32.6%), and AST increase (32.6%); Most were Grade 1 or 2. Conclusions: RC48-ADC has demonstrated a clinically meaningful ORR of 60.5% in pretreated HER-2 positive mUC patients including those who underwent failure to the immunotherapy. Clinical trial information: NCT03507166.

ENVASARC: A pivotal trial of envafolimab, and envafolimab in combination with ipilimumab, in patients with advanced or metastatic undifferentiated pleomorphic sarcoma or myxofibrosarcoma who have progressed on prior chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS11581-TPS11581
Author(s):  
Sandra P. D'Angelo ◽  
Steven Ian Robinson ◽  
Joelle Lam ◽  
Bonne J. Adams ◽  
James L. Freddo ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Objective Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Locally Advanced ◽  
Primary Objective ◽  
Open Label ◽  
Undifferentiated Pleomorphic Sarcoma ◽  
Pleomorphic Sarcoma

TPS11581 Background: Metastatic undifferentiated Pleomorphic Sarcoma (UPS) and the genetically related myxofibrosarcoma (MFS) are soft tissue sarcoma (STS) subtypes with poor prognoses. While responses to front line chemotherapy can approach 20%, efficacy remains limited in the 2nd line setting and beyond. Pazopanib, the only approved treatment in the refractory setting, has demonstrated an objective response rate (ORR) of 4%. Envafolimab is a single domain PD-L1 antibody administered rapidly by subcutaneous (SQ) injection that is being studied in two additional pivotal trials: microsatellite instability-high (MSI-H) cancer and biliary tract cancer. The activity of envafolimab appears to be similar to other PD-1 antibodies administered i.v. Envafolimab demonstrated a 32% objective response rate (ORR) in MSI-H colorectal cancer patients who failed three approved chemotherapeutics, similar to the ORR of 28% and 33% with nivolumab and pembrolizumab in these patient populations, respectively. The rationale for the ENVASARC trial is based on the previously reported activity of checkpoint inhibition in UPS/MFS. Single agent pembrolizumab demonstrated a 23% ORR, while the combination of nivolumab and ipilimumab demonstrated a 29% ORR in refractory UPS/MFS. Methods: ENVASARC (NCT 04480502) is a pivotal multicenter (at ̃25 U.S. centers) open-label, randomized, non-comparative, parallel cohort study of treatment with envafolimab 300 mg every 3 weeks by SQ injection (cohort A; n = 80) or envafolimab 300 mg every 3 weeks by SQ injection combined with ipilimumab 1 mg/kg every 3 weeks i.v. for four doses (cohort B; n = 80) in patients with locally advanced, unresectable or metastatic UPS/MFS who have progressed on one or two lines of prior therapy. The primary objective of each of parallel cohort is to demonstrate an ORR with a lower limit of the 95% confidence interval that excludes 5.0% in each cohort. If ≥ 9 responders are observed of the 80 patients enrolled in each cohort, then the lower bound of the 95% confidence interval will exclude 5.0%. Secondary endpoints include duration of response (DOR), PFS and OS. Key inclusion criteria: ≤ 2 prior lines of therapy (neoadjuvant and adjuvant therapy excluded), ECOG ≤ 1. Clinical trial information: NCT 04480502.

Clinical significance of Ki-67 index expression in advanced non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20576-e20576
Author(s):  
Di ming Wang ◽  
Qingming Shi
Keyword(s):  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Squamous Carcinoma ◽  
Progression Free Survival ◽  
Tumor Stage ◽  
Ki 67 ◽  
Free Survival ◽  
Response To Chemotherapy ◽  
The Relationship

e20576 Background: It is unclear how the Ki-67 index expression affects the objective response to chemotherapy in non-small cell lung cancer(NSCLC). The study analyzed the relationship among the Ki-67 index, the objective response rate and progression-free survival(PFS) of chemotherapy in ad-NSCLC. Methods: 112 patients of advanced NSCLC in our hospital from 2014 to 2017 were studied. Both EGFR and ALK were wild type in adenocarcinoma patients, and no gene test was performed in squamous carcinoma. The relationship among Ki-67 index ,tumor stage, response of chemotherapy and progression-free survival was analyzed by univariate and multivariate analysis.Ki-67 index was used to predict the objective response of chemotherapy by receiver operating characteristic curve(ROC curve). Results: The objective response rate of chemotherapy was 61.6%(69/112);squamous carcinoma was 69.1%(38/55);adenocarcinoma was 54.4%(31/57). Ki-67 index(P = 0.000) and tumor stage(P = 0.025) were the factors influencing the objective efficacy of chemotherapy.Ki-67 index was linearly correlated with tumor stage (r = 0.341,P = 0.001).In the univariate and multivariate analyses, the Ki-67 index was significantly associated with the objective response to chemotherapy (B = -0.069,P = 0.000).Ki-67 index expression can accurately predict the objective response rate of ad-NSCLC chemotherapy by ROC curve(P < 0.0001,AUC = 0.7467,95%CI = 0.6578-0.8356):squamous carcinoma group (P = 0.0003,AUC = 0.8065,95%CI = 0.6922- 0.9208), adenocarcinoma group (P = 0.0193, AUC = 0.681,95%CI = 0.536-0.8262).In the test cohort, the sensitivity of the Ki-67 index to the objective response rate of chemotherapy was 93.02%.In the squamous carcinoma group the sensitivity was 94.12%.In the adenocarcinoma group the sensitivity was 65.54%.The best Cut-off was 55% for the adenocarcinoma group with good chemotherapeutic efficacy and the adenocarcinoma group with poor efficacy. The best Cut-off value was 65% in squamous carcinoma group with good curative effect and squamous carcinoma group with poor curative effect.The overexpression of Ki-67 index was a negative prognostic factor for PFS in ad-NSCLC (P < 0.0001):squamous carcinoma (P = 0.0055), adenocarcinoma (P < 0.0001). In multivariate Cox analysis, Ki-67 index (P = 0.000) and stage (P = 0.001) were negative factors of PFS. Conclusions: Ki-67 index is a clinically significant biomarker in ad-NSCLC, which can predict the objective efficacy of chemotherapy. The high expression of Ki-67 might be an indicator of the shortened PFS time.

Follow-Up of Patients With Complete Remission of Locally Advanced Basal Cell Carcinoma After Vismodegib Discontinuation: A Multicenter French Study of 116 Patients

2019 ◽  
Vol 37 (34) ◽  
pp. 3275-3282 ◽  
Author(s):  
Florian Herms ◽  
Jerome Lambert ◽  
Jean-Jacques Grob ◽  
Luc Haudebourg ◽  
Martine Bagot ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Basal Cell Carcinoma

PURPOSE Vismodegib is a hedgehog pathway inhibitor indicated for the treatment of locally advanced basal cell carcinoma (laBCC), with an objective response rate of 65%, including a 32% complete response (CR). However, adverse effects often lead to drug discontinuation. The objective of our study was to evaluate long-term responses, predictive factors, and management of relapse after vismodegib discontinuation. METHODS An observational retrospective study was conducted in nine French oncodermatology units. We included patients with laBCC with CR on vismodegib who discontinued treatment between March 2012 and January 2016; we reviewed charts up to June 2016. The primary objective was to evaluate median relapse-free survival (RFS). Secondary objectives were risk factors associated with RFS, relapse, and death and treatment modalities after relapse and their efficacy. RESULTS One hundred sixteen patients with laBCC were included. The median RFS was 18.4 months (95% CI, 13.5 to 24.8 months). The RFS rate at 36 months was 35.4% (95% CI, 22.5% to 47.9%) for the total population and 40.0% (95% CI, 25.7% to 53.7%) for patients without Gorlin syndrome. LaBCC to the limbs and trunk was the only variable independently associated with a higher risk of relapse (hazard ratio, 2.77; 95% CI, 1.23 to 6.22; P = .019). Twenty-seven patients (50%) who experienced relapse during follow-up were retreated with vismodegib, with an objective response in 23 (objective response rate, 85%; CR rate, 37%; partial response rate, 48%) and eligibility for surgery in 24 (42%). CONCLUSION Long-term response after vismodegib discontinuation is frequent. Most patients who experience a relapse still respond to vismodegib rechallenge.

Randomized Phase III Evaluation of Cisplatin Plus Fluorouracil Versus Cisplatin Plus Paclitaxel in Advanced Head and Neck Cancer (E1395): An Intergroup Trial of the Eastern Cooperative Oncology Group

2005 ◽  
Vol 23 (15) ◽  
pp. 3562-3567 ◽  
Author(s):  
Michael K. Gibson ◽  
Yi Li ◽  
Barbara Murphy ◽  
Maha H.A. Hussain ◽  
Ronald C. DeConti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Response Rate ◽  
Cell Cancer ◽  
Objective Response ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Complete Response ◽  
Phase Iii ◽  
Significant Difference

Purpose To determine the response rate, survival and toxicity of infusional cisplatin plus fluorouracil (CF) versus cisplatin plus paclitaxel (CP) in patients with incurable squamous cell cancer of the head and neck, with the hypothesis that CP is superior. Patients and Methods Two hundred eighteen patients with locally advanced, recurrent, or metastatic disease were randomly assigned to CF (cisplatin 100 mg/m2 day 1 and fluorouracil 1,000 mg/m2/24 hours by continuous intravenous infusion day 1 through 4) or CP (cisplatin 75 mg/m2 day 1 and paclitaxel 175 mg/m2 over 3 hours on day 1). Cycles were repeated every 3 weeks until progression or a minimum of 6 cycles with complete response or stable disease. The primary outcome was overall survival. Secondary outcomes included response rate and toxicity. Results No significant difference in overall survival or response rate was seen. Estimated median survival was 8.7 months in the CF group and 8.1 month in the CP group. Objective response rate (complete response plus partial response) was 27% in the CF group and 26% in the CP group. Toxicity was similar between groups, with the most frequent including myelosuppression, thrombocytopenia, anemia, nausea, vomiting, and stomatitis. A total of 12 deaths occurred (CF, seven; CP, five) during treatment; eight from infection, two from hemorrhage, one from cardiac causes and one from unknown causes. Gastrointestinal and hematologic toxicities were more common in the CF group, whereas neurotoxicity was equivalent between groups. Conclusion This phase III, randomized, multicenter trial showed no difference in survival between patients treated with CF or CP.

scholarly journals Imatinib Mesylate in Advanced Dermatofibrosarcoma Protuberans: Pooled Analysis of Two Phase II Clinical Trials

2010 ◽  
Vol 28 (10) ◽  
pp. 1772-1779 ◽  
Author(s):  
Piotr Rutkowski ◽  
Martine Van Glabbeke ◽  
Cathryn J. Rankin ◽  
Wlodzimierz Ruka ◽  
Brian P. Rubin ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Dermatofibrosarcoma Protuberans ◽  
Phase Ii Trials ◽  
Two Phase ◽  
End Point ◽  
Best Response

Purpose Dermatofibrosarcoma protuberans (DFSP) is a dermal sarcoma typically carrying a translocation between chromosomes 17 and 22 that generates functional platelet-derived growth factor B (PDGFB). Patients and Methods Two distinct phase II trials of imatinib (400 to 800 mg daily) in patients with locally advanced or metastatic DFSP were conducted and closed prematurely, one in Europe (European Organisation for Research and Treatment of Cancer [EORTC]) with 14-week progression-free rate as the primary end point and the other in North America (Southwest Oncology Group [SWOG]) with confirmed objective response rate as the primary end point. In the EORTC trial, confirmation of PDGFB rearrangement was required, and surgery was undertaken after 14 weeks if feasible. The SWOG study confirmed t(17;22) after enrollment. Results Sixteen and eight patients were enrolled onto the EORTC and SWOG trials, respectively. Tumor size ranged from 1.2 to 49 cm. DFSP was located on head/neck, trunk, and limb in seven, 11, and six patients, respectively, and was classic, pigmented, and fibrosarcomatous DFSP in 13, one, and nine patients, respectively. Metastases were present in seven patients (lung involvement was present six patients). Eleven patients (4%) had partial response as best response, and four patients had progressive disease as best response. Median time to progression (TTP) was 1.7 years. Imatinib was stopped in 11 patients because of progression, one patient because of toxicity, and two patients after complete resection of disease. Median overall survival (OS) time has not been reached; 1-year OS rate was 87.5%. Conclusion Imatinib is active in DFSP harboring t(17;22) including fibrosarcomatous DFSP, with objective response rate approaching 50%. Response rates and TTP did not differ between patients taking 400 mg daily versus 400 mg twice a day.

scholarly journals Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations

2021 ◽  
pp. JCO.20.02903
Author(s):  
Alan L. Ho ◽  
Irene Brana ◽  
Robert Haddad ◽  
Jessica Bauman ◽  
Keith Bible ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Neck Squamous Cell Carcinoma ◽  
Additional Patient ◽  
Open Label

PURPOSE Mutations in the HRAS (m HRAS) proto-oncogene occur in 4%-8% of patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Tipifarnib is a farnesyltransferase inhibitor that disrupts HRAS function. We evaluated the efficacy of tipifarnib in patients with R/M m HRAS HNSCC. METHODS We enrolled 30 patients with R/M HNSCC in a single-arm, open-label phase II trial of tipifarnib for m HRAS malignancies; one additional patient was treated on an expanded access program. After an ad hoc analysis of the first 16 patients with HNSCC with m HRAS variant allele frequency (VAF) data, enrollment was limited to those with a m HRAS VAF of ≥ 20% (high VAF). The primary end point was objective response rate. Secondary end points included assessing safety and tolerability. Patients received tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles. RESULTS Of the 22 patients with HNSCC with high VAF, 20 were evaluable for response at the time of data cutoff. Objective response rate for evaluable patients with high-VAF HNSCC was 55% (95% CI, 31.5 to 76.9). Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy. Median overall survival was 15.4 months (95% CI, 7.0 to 29.7). The most frequent treatment-emergent adverse events among the 30 patients with HNSCC were anemia (37%) and lymphopenia (13%). CONCLUSION Tipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC with HRAS mutations for whom limited therapeutic options exist ( NCT02383927 ).

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