Impact of MET inhibitors on survival among patients (pts) with MET exon 14 mutant (METdel14) non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8511-8511 ◽  
Author(s):  
Mark M. Awad ◽  
Giulia Costanza Leonardi ◽  
Sasha Kravets ◽  
Suzanne Eleanor Dahlberg ◽  
Alexander E. Drilon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Sarcomatoid Carcinoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Driver Mutations ◽  
Rank Test ◽  
Cox Models ◽  
Significant Prolongation ◽  
Met Amplification ◽  
Met Inhibitor

8511 Background: Dramatic responses to MET inhibitors have been reported in patients with NSCLC harboring activating mutations that cause MET exon 14 ( METdel14) skipping. We conducted a multicenter retrospective analysis of pts with METdel14 NSCLC to determine if treatment with MET inhibitors impacts survival. Methods: We collected clinicopathologic data on pts with METdel14 NSCLC. Event-time distributions were estimated using Kaplan-Meier and compared with the log-rank test. Multivariable Cox models were fitted to estimate hazard ratios. Results: Of the 148 pts with METdel14 mutant NSCLC, the median age was 72 (range 43-88); 57% were women, and 41% were never smokers. The most common histologies were adenocarcinoma (77%) and pulmonary sarcomatoid carcinoma (14%). Overlap with oncogenic driver mutations in other genes was rare. At the time of diagnosis, 70% of pts had stage I-III disease, and 30% had stage IV disease. Of the 34 pts with metastastic disease who never received a MET inhibitor, the median overall survival (mOS) was 8.1 months. In this cohort, cancers that also had concurrent MET amplification had a trend toward worse survival compared to cancers without MET amplification (5.2 months vs 10.5 months, P = 0.06). Of the 27 pts with metastatic disease who received at least one MET inhibitor (including crizotinib, glesatinib, capmatinib, and ABBV-399), the mOS was 24.6 months. A model adjusting for receipt of a MET inhibitor as first- or second-line therapy as a time-dependent covariate demonstrated that treatment with a MET inhibitor was associated with a significant prolongation in survival (HR 0.11, 95% CI 0.01-0.92, P = 0.04). Among 22 patients treated with crizotinib, the median progression-free survival (PFS) was 7.36 months. Conclusions: Forpts with METdel14 NSCLC, treatment with a MET inhibitor is associated with an improvement in overall survival. The prognosis of pts who never received treatment with a MET inhibitor appears to be poor, particularly among METdel14 cancers with concurrent MET amplification.

Prognosis and comorbidities in stage III and IV endometrial cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16553-e16553
Author(s):  
K. Wright ◽  
E. Munro ◽  
M. del Carmen ◽  
A. K. Goodman
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Stage Iv ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Rank Test ◽  
Laboratory Values ◽  
Significant Difference ◽  
Baseline Creatinine

e16553 Background: While endometrial cancer may be associated with many comorbid conditions, none have been characterized as changing overall prognosis. The aim of this study was to identify medical conditions or laboratory values, that may serve as prognostic factors in stage III and IV endometrial cancer. Methods: A retrospective chart review identified 112 women with stage III or IV endometrial cancer between years 1993–1998. Information about medical comorbidities and presenting lab values were collected using electronic medical records. Progression free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier survival method and the log rank test. Results: The average age was 64.9 yrs. 79 women (70.5%) had stage III disease and 33 women (29.5%) had stage IV disease. For those with a baseline creatinine <1.2 (n = 91), the PFS and OS were not significantly different from those with a baseline creatinine ≥1.2 (n = 17; p = 0.554 and p = 0.487, respectively). There was a non-significant trend toward worse PFS for the 41 patients with hypertension (HTN) compared to the 62 without (48.0 and 61.2 months, p = 0.191). The overall survival was significantly worse for those with HTN (38.7 months vs. 56.0 months p = 0.046). For those with known coronary artery disease, no significant difference in PFS or OS was found (p = 0.792 and p = 0.312 respectively). Those with diabetes (n = 15) did not have a significantly different PFS compared to those who did not (n = 88; p = 0.728). The OS was worse at 20.1 months for those with diabetes compared to 54.3 months for those without (p = 0.001). Baseline albumin had a significant effect on both PFS and OS. Those with an albumin <3.5 (n = 54) had a PFS of 46.2 months compared to 94.0 months for those with an albumin ≥3.5 (n = 23; p = 0.007), and the OS for those with low albumin was 44.8 months compared to 83.4 months for those with the higher albumin (p = 0.005). Conclusions: These results suggest that past medical history and some baseline laboratory values may be important in considering prognosis. In particular, patients with a history of HTN or diabetes have a worse overall survival. Those with a baseline albumin of <3.5 have a worse PFS and OS. No significant financial relationships to disclose.

scholarly journals Efficacy of Panitumumab and Cetuximab in Patients with Colorectal Cancer Previously Treated with Bevacizumab; a Combined Analysis of Individual Patient Data from ASPECCT and WJOG6510G

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1715
Author(s):  
Hiroya Taniguchi ◽  
Takeharu Yamanaka ◽  
Daisuke Sakai ◽  
Kei Muro ◽  
Kentaro Yamazaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Clinical Trial Registration ◽  
Cox Models ◽  
Exon 2 ◽  
Free Survival ◽  
Previously Treated

Background: Phase-III ASPECCT and randomised phase-II WJOG6510G trials demonstrated the noninferiority of panitumumab, when compared with cetuximab, for overall survival in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. Methods: The subgroup that received bevacizumab either prior to panitumumab or cetuximab monotherapy (ASPECCT) or in combination with irinotecan (WJOG6510G) was included. Multivariate Cox models were created, including the treatment arms as covariates together with patient, disease and treatment characteristics. Results: We included 185 and 189 patients in the panitumumab and cetuximab arms, respectively. The median overall survival was 12.8 and 10.1 months [p = 0.0031; log-rank test, stratified by trial; hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58–0.90], and the median progression-free survival was 4.7 and 4.1 months, in the panitumumab and cetuximab arms, respectively (p = 0.0207; HR, 0.79; 95% CI, 0.64–0.97). The treatment regimen was an independent prognostic factor of overall survival (adjusted HR, 0.69; 95% CI, 0.54–0.87; p = 0.0013). Conclusions: Panitumumab significantly prolonged the overall survival and progression-free survival, when compared with cetuximab in the cohort that previously received bevacizumab in the included studies. Clinical Trial Registration: ASPECCT trial registered with ClinicalTrials.gov (NCT01001377) and WJOG6510G trial registered with UMIN-CTR (UMIN000006643).

Number of cycles of chemotherapy in patients with advanced non-small cell lung caner: Efficacy and relationship with histology.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18125-e18125
Author(s):  
Eduardo Richardet ◽  
Martin Eduardo Richardet ◽  
Nicolas Castagneris ◽  
Matias Nicolas Cortes ◽  
Perelli Laura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Rank Test ◽  
Test Results ◽  
First Line ◽  
Free Survival ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Number Of Cycles

e18125 Background: Platinum based regimens are standard first-line treatment in patients with advanced non mall cell lung cancer. We intend to evaluate their effectiveness according to the number of cycles administered, and investigate whether histology is a predictor of benefit from a greater number of infusions. Methods: 124 patients with stage IV NSCLC were evaluated retrospectively. They were divided according to whether they made 4 or 6 cycles of chemotherapy. The schemes used were: Cisplatin / Gemcitabine and Carboplatin / Paclitaxel, at standard doses. We studied the efficacy in both groups according to the most common histologies (adenocarcinoma and squamous cell carcinoma). PFS (progression-free survival) and OS (overall survival) were calculated by the Kaplan-Meier curves and compared by the Log Rank Test. Results: Those who underwent 4 cycles had a PFS of 7.77 months and OS of 12.2 months vs. 8.64 and 10.8 months those who received 6 cycles (p = 0.47, p = 0.76). Within the subgroup with squamous histology (n = 43), PFS and OS were 7.38 and 13.38 months respectively in the group that received 4 cycles vs. 7.97 and 9.76 months in those receiving 6 (p = 0.70, p = 0.32 ). Within adenocarcinoma histology (n = 81), those who received 4 cycle, has a PFS of 8.17 months and they lived 11.56 month, vs 8.96 and 10.79 months for those receiving 6 cycles (p = 0.29, p = 0.88) Conclusions: In our population, a greater number of cycles showed no advantages in terms of progression-free survival or overall survival. Histology is not a predictive factor for deciding how many chemotherapy cycles administer.

Long-term survival of de novo stage IV human epidermal growth factor receptor 2 (HER2)-positive breast cancers treated with HER2 targeted therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1021-1021 ◽  
Author(s):  
Yao Wong ◽  
Akshara Singareeka Raghavendra ◽  
Christos Hatzis ◽  
Javier Perez Irizarry ◽  
Teresita Vega ◽  
...  
Keyword(s):  
Overall Survival ◽  
Targeted Therapies ◽  
De Novo ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Rank Test ◽  
Her2 Positive ◽  
Free Survival ◽  
Log Rank Test ◽  
Her 2

1021 Background: An increasing number of metastatic HER2 positive cancers represent de novo stage IV disease as fewer early stage patients relapse. We hypothesize that a subset of these has long progression free survival (PFS) after initial combined modality HER2-targeted therapies. Methods: 483 patients with de novo stage IV HER2 positive breast cancer diagnosed between 1998-2015 were identified through the medical records at Yale and MD Anderson Cancer Centers, respectively. Treatment, clinical variables and survival were extracted and compared between those who achieved “no evidence of disease” (NED) status with initial therapy and those who did not. Results: All patients received trastuzumab and 94 (20%) also received pertuzumab as first line therapy.The median OS was 5.5 years (95% Cl: 4.8-6.2); OS rates at 5 and 10 years were 54% (95% CI: 48%-60.4%) and 18% (95% Cl: 11.4%-28.3%), respectively and PFS were 41% (95% CI: 35%-48%) and 41% (95% CI: 35%-48%). Sixty-three patients (13.0%; 95% CI: 10.2% -16.4%) achieved NED. The PFS and OS at 5 and 10 years were the same 100% and 98% (95% CI: 94.6%-100%), respectively. For patients with no-NED (n = 420), the median OS was 4.7 years (95% Cl: 4.2-5.3), the PFS and OS rates at 5 and 10 years were 12% (95% CI: 4.5%-30.4%) and 0% and 45% (95% CI: 38.4%-52.0%) and 4% (95% CI: 1.3%-13.2%), respectively. NED patients had significantly longer progression free survival (log-rank test p≤0.001) and overall survival (log-rank test p≤0.001), more frequently had single organ site metastasis (76% vs 57%, p = 0.005), and more frequently had surgery for primary tumor (59% vs. 25%, p ≤0.001) than no-NED patients, but there was no significant difference in age, grade, race, year of diagnosis, ER status, treatment distribution, or radiation between the groups. Conclusions: About 13% of de novo, stage IV, HER-2 positive MBC patients achieved NED with HER-2 targeted therapies, all of these patients were progression free at 5 years and overall survival at 10-years was 98% compared to 4% among those with no-NED in our data sets. These results suggest that aggressive multimodality therapy of newly diagnosed stage IV HER2 positive cancers to render them NED may be warranted.

Toxicities of axitinib, sunitinib and temsirolimus: implications for progression-free and overall survival in metastatic renal cell cancer

2020 ◽  
Author(s):  
Annemarie Uhlig ◽  
Johannes Uhlig ◽  
Lutz Trojan ◽  
Michael Woike ◽  
Marianne Leitsmann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Skin Reaction ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Cox Models ◽  
Metastatic Renal Cell Cancer ◽  
Hand Foot Skin Reaction

The aim of this study was to evaluate the association between axitinib, sunitinib and temsirolimus toxicities and patient survival in metastatic renal cell cancer patients. Overall survival (OS) and progression-free survival (PFS) of metastatic renal cell cancer patients from the prospective multicenter STAR-TOR study were assessed using multivariable Cox models. A total of 1195 patients were included (n = 149 axitinib; n = 546 sunitinib; n = 500 temsirolimus). The following toxicities significantly predicted outcomes: hand–foot skin reaction (hazard ratio [HR] = 0.29) for PFS with axitinib; stomatitis (HR = 0.62) and pneumonitis (HR = 0.23) for PFS with temsirolimus; stomatitis (HR = 0.52) and thrombocytopenia (HR = 0.6) for OS with temsirolimus; fatigue (HR = 0.71) for PFS with sunitinib; hand–foot skin reaction (HR = 0.56) and fatigue (HR = 0.58) for OS with sunitinib. In conclusion, in metastatic renal cell cancer, axitinib, sunitinib and temsirolimus demonstrate specific toxicities that are protective OS/PFS predictors.

LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

2021 ◽  
pp. 1-9
Author(s):  
Ankita Gupta ◽  
Budhi Singh Yadav ◽  
Nagarjun Ballari ◽  
Namrata Das ◽  
Ngangom Robert
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Progression Free Survival ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

scholarly journals Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Free Survival

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

The predictive value of MAP2K1/2 mutations for efficiency of immunotherapy in melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21587-e21587
Author(s):  
Ting Ye ◽  
Jieying Zhang ◽  
Xinyi Liu ◽  
Mengmei Yang ◽  
Yuhan Zhou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Predictive Value ◽  
Cox Regression ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Driver Mutations ◽  
Cox Regression Analysis ◽  
Melanoma Patients ◽  
The Impact

e21587 Background: Immunotherapies targeting immune checkpoint receptors have become the cornerstone of systemic treatment options for malignant melanoma. The response to these immunotherapies may correlate with driver mutations. MAP2K1/2 genes are mutated in approximately 10% of melanomas, however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. Methods: Six metastatic melanoma clinical cohorts treated with ICIs were included to investigate the association between clinical efficacy of immunotherapy and MAP2K1/2 mutations. Survival analyses were conducted in cohorts receiving two kinds of ICB agents, namely anti-CTLA-4 or anti-PD-1. RNA expression profiling from these cohorts and from the TCGA melanoma cohort were used to explore the potential mechanism related to immune activation. Results: In an independent anti-CTLA-4-treated cohort (n = 110), we found that MAP2K1/2 mutations are predictive of high objective response rate (17.6% vs 1.3%, p = 0.0185) and long progression-free survival [median OS, 49.2 months vs 8.3 months; hazard ratio (HR) = 0.37; 95% CI, 0.15–0.91; p = 0.0307] and overall survival (median PFS, 19.4 months vs 2.8 months; HR = 0.2; 95% CI, 0.05–0.83; p = 0.0262). This predictive value was further validated in a pooled anti-CTLA-4-treated cohort (n = 235) in terms of overall survival (median OS, 49.3 months vs 22.0 months; HR = 0.44; 95% CI, 0.22–0.91; p = 0.0255). However, no correlation between MAP2K1/2 mutations and overall survival was observed in the anti-PD-1-treated cohort (n = 285). Subgroup Cox regression analysis indicated that MAP2K-mutated patients receive less benefit from the anti-PD-1 monotherapy than from the anti-CTLA-4 treatment (median OS, 27.0 months vs 49.3 months; HR = 3.26; 95% CI, 1.18–9.02; p = 0.0225), which was contrary to the result obtained for the total population. Furthermore, transcriptome profiling analysis revealed that MAP2K-mutated tumors are enriched in CD8+ T cells, B cells, and neutrophil cells and also express high levels of CD33 and IL10, which might be the underlying mechanism for melanoma patients with MAP2K1/2-mutated benefit more from anti-CTLA-4 treatment. Conclusions: We identified mutations in MAP2K1/2 genes as the independent predictive factors for anti-CTLA-4 therapy in melanoma patients and found that anti-CTLA-4 treatment in patient harbouring MAP2K1/2 mutations might be more effective than the anti-PD-1 therapy.

TRYHARD, a randomized phase II trial (RTOG Foundation 3501) of concurrent accelerated radiation plus cisplatin (cis) with or without lapatinib (Lap) for stage III- IV Non-HPV head and neck carcinoma (HNC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6014-6014
Author(s):  
Stuart J. Wong ◽  
Pedro A. Torres-Saavedra ◽  
Nabil F. Saba ◽  
George Shenouda ◽  
Jeffrey Bumpous ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Stage Iii ◽  
Adverse Event Rate ◽  
Rank Test ◽  
Days Of Therapy ◽  
Grade 3

6014 Background: Chemoradiation (CRT) with cis or anti-EGFR Ab has been shown to improve survival of patients with stage III-IV HNC. Since Lap, a dual EGFR and HER2 inhibitor, has shown effectiveness with CRT in a pilot non-HPV HNC cohort, the RTOG Foundation launched a phase II trial to test the hypothesis that adding Lap to the RT-cis for frontline therapy of stage III-IV Non-HPV HNC improves progression-free survival (PFS). Methods: Patients with stage III-IV carcinoma of the oropharynx (p16-negative), larynx, and hypopharynx, having Zubrod performance of 0-1, and meeting predefined blood chemistry criteria were enrolled after providing consent. Patients were randomized (1:1) to 70 Gy (6 weeks) + 2 cycles of CDDP (q3 weeks) plus either Lap (1500 mg daily, Arm A) or placebo (Arm B) starting 1 week prior to RT and concurrent with RT and for 3 months post RT. PFS was the primary endpoint. The protocol specified 69 PFS events (142 patients) for the final analysis based on HR = 0.65, 80% power, 1-sided alpha 0.20, and one interim efficacy and futility analysis at 50% information. PFS rates between arms for all randomized patients were compared by 1-sided log-rank test (1-sided alpha 0.1803). Overall survival (OS) was a secondary endpoint. Results: From 10/’12 to 04/’17, 142 patients were enrolled, of whom 127 were randomized, 63 to Arm A and 64 to Arm B. Arms A vs B, respectively, were similar in baseline patient characteristics, radiation delivery, completing ≥ 70 Gy (85.7% vs. 82.8%) and cisplatin delivery, completing 200 (±5%) mg/m2 (65.1% vs 70.3%), but dissimilar in Lap/placebo delivery (median dose, 87000 mg vs. 125250 mg). Median follow-up was 4.1 years for surviving patients. The final analysis suggests no improvement in PFS of adding Lap to CRT (HR [A/B]: 0.91, 95% confidence interval CI 0.56-1.46; P= 0.34; 2-year rates: 50.6%, CI 37.5-63.7% vs. 56.2% CI 43.0-69.4%), or in OS (HR: 1.06, CI 0.61-1.86; P = 0.58; 2-year rates: 71.8% CI 60.1-83.5% vs. 76% CI 64.5-87.4%), death within 30 days of therapy (3.3% vs. 3.4%), and overall treatment-related grade 3-5 adverse event rate (86.7% vs. 84.7%). Grade 3-4 mucositis rates on Arm A and Arm B were 21.7% vs. 23.7%, all grade dysphagia and rash rates were 43.3% vs. 59.3%, and 13.3% vs. 6.8%, respectively. Conclusions: The addition of Lap to the radiation-cisplatin platform did not improve progression-free or overall survival in unselected non-HPV HN. Thus, dual EGFR, HER-2 inhibition does not appear to enhance the effects of chemoradiation. Although we showed that accrual to a non-HPV HN specific trial is feasible, new strategies must be investigated to improve the outcome for this poor prognosis HN population.

Characterization of BCL-2 alternative proteins and outcome in patients with peripheral T-cell lymphoma (PTCL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19531-e19531
Author(s):  
Mario L. Marques-Piubelli ◽  
Luisa Maren Solis ◽  
Luis Malpica ◽  
Sushant Gouni ◽  
Ranjit Nair ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
Rank Test ◽  
Cell Transplant ◽  
Functional Studies ◽  
Tissue Biopsy ◽  
Previously Treated

e19531 Background: The outcome of patients with PTCL, NOS is generally very poor, and the identification of biologically rational targets, which may translate into effective and non-toxic treatment strategies, is a high priority. The pro-survival BCL-2 family members BCL-2, BCL-XL (BCL2L1), BCL-W (BCL2L2), BCL2A1 and MCL-1 contribute to tumor maintenance, progression, and chemo-resistance across a range of cancers, but their contributions in PTCL, NOS are poorly understood. Methods: Patients with PTCL, NOS treated between 09/2000 and 09/2019 and with available tissue biopsy were included in the study. Diagnosis was retrospectively confirmed by two expert hematopathologists. BCL-2, BCL-XL, BCL-W, BCL2A1 and MCL-1 expression was assessed by immunohistochemistry (IHC), and the percentage of positive tumor cells assessed by standard microscopy. The 2014 Lugano Classification was used to define response to therapy. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and were compared using log-rank test between patient groups. Results: Twenty-seven patients were included in the study: 67% were male, 52% ≥ 65 year old, and 48% had stage IV disease; 59% were previously treated and 41% received > 2 lines of therapy, including stem cell transplant (SCT) in 19%. The median expression of BCL-2, BCL-XL, BCL-W, BCL2A1 and MCL-1 by IHC was: 30% (range: 0-100%), 10% (range: 0-90%), 100% (range: 40-100%), 20% (range: 0-90%), and 70% (range: 1-100%), respectively. BCL-2A1 was significantly higher in previously treated patients (35% vs 5%, p = 0.02), and in those who had previously received > 2 lines of therapy (40% vs 5%, p = 0.02). Twenty-four (89%) patients were treated after tissue biopsy, 17 (63%) with chemotherapy, 7 (26%) with biological therapy, and 6 (22%) received subsequent SCT. Five (24%) patients achieved complete remission (CR); only BCL-W associated with response, a higher expression (quartiles 3 and 4) being observed among patients not achieving CR (median 100% vs 90%, p = 0.07). After a median follow-up of 28 months (95% CI, 14-42 months), 22 (81%) patients progressed or died, and median PFS was 4 months (95% CI, 2-6 months); only BCL-W associated with PFS, a shorter median PFS being observed for patients with higher expression (3 months vs 7 months, p = 0.001). At most recent follow-up, 17 (63%) patients died, and median OS was 6 months (95% CI, 1-12 months). only BCL-W associated with OS, a shorter median OS being observed for patients with higher expression (4 months vs not reached, p = 0.004). Conclusions: High expression of BCL-W associates with significantly worse outcome in patients with PTCL, NOS. While clinical trials investigating the safety and efficacy of BCL-2 inhibition in PTCL, NOS are ongoing, these results suggest that concomitant BCL-W inhibition may be beneficial, and functional studies aimed at confirming these findings are highly needed.

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