e20539 Background: The PACIFIC trial ushered in a paradigm shift in the management of unresectable, non-metastatic non-small cell lung cancer (NSCLC), demonstrating improvement in 12,24,36-month overall survival (OS) and leading to the 2018 FDA approval for durvalumab in unresectable or locally advanced stage III NSCLC. With almost 3 years of FDA approval, we performed a retrospective analysis of patient experiences and outcomes at Levine Cancer Institute analyzing patient data to assess survival and potential points of clinical significance. Methods: Patients over the age of 18, who met criteria similar to the PACIFIC trial (i.e. unresectable or locally advanced stage III NSCLC) from February 2018 through September 2020 were analyzed. Those who were receiving active treatment at the data cutoff were excluded. Patient characteristics, prior treatment, durvalumab administration, immune-related adverse events (irAEs), and efficacy data were summarized and evaluated. OS and progression free survival (PFS) were evaluated with Kaplan Meier methods. Results: A total of 159 patients were evaluated. 40.9% were female and 59.1% were male. The median age was 67 (range 38-83 years). Of note, 86.8% of patients were white, whereas 13.2% were nonwhite. 50.3% patients experienced an irAE. The most common reasons for discontinuation of durvalumab were completion (at least 24 doses), progressive disease, or toxicity (33.3%, 30.8%, 26.4%, respectively). The median number of doses of durvalumab received was 14 (range 1-26 doses). The median PFS was 15.3 months with 12-and 24-month PFS being 54% and 41.1 %, respectively. Median OS was 42 months with 12-and 24-month OS being 78.1% and 67.8%, respectively. Our analysis compared outcomes in those who completed adjuvant durvalumab versus those who did not complete adjuvant therapy (Table). Conclusions: Data shows the best survival in those who completed durvalumab (comparable to historic values) and novel data shows a perceived survival benefit in those completing 12 doses compared to those who did not. Thus, partial treatment may provide a survival advantage. Further multivariate analysis will look for possible correlations to increased immune events and inability to complete therapy. Further investigation will delve into this cohort’s small proportion of non-white patients, evaluating for possible barriers to care that may lead to more patients being diagnosed with stage IV NSCLC.[Table: see text]
Background: In the U.S., around 252,710 new breast cancer cases will be diagnosed in the year 2017. About 15-20% of these patients will be candidates for treatment with Her-2 directed therapy. The College of American Pathologists (CAP) published initial guidelines for immunohistochemistry (IHC) in 2003 with revisions in 2007 and 2013. 2013 guidelines define 3+(positive) as >10% intense complete membrane staining similar to 2003; >30% complete in 2007. Equivocal 2+ category in 2013 includes incomplete staining > 10% for the first time; this was negative in 2003 and 2007.Hypothesis: The 2013 guidelines do not result in more true positives but increased equivocal cases resulting in clinical uncertainty and increased cost. Methods : A retrospective analysis was performed of all IHC and FISH testing done at a single institution with a single pathology reader from 2003-2016. Criteria for IHC and FISH positivity were followed for each time period and compared to one another for positive and negative HER2 expression. The equivocal categories than compared for outcome by FISH. Ultimate numbers for percentage in each category compared for statistical significance. Results: IHC NegativeEquivocalPositiveTotal(1) 2003279, 70.6%71, 17.9%45, 11.3%395(2) 2007187, 71.6%49, 18.7%25, 9.5%261(3) 2013181, 61.7%79, 26.9%33, 11.2%293Total647199103949Chi-SquareDFValueProbOverall410.40.03 Period 1 vs 220.50.75Period 1 vs 328.20.01Period 2 vs 326.40.04 IHC Equivocal Reflex to FISH NegativeEquivocalPositiveTotal(1) 200358, 82.8%1, 1.4%11, 15.7%70(2) 200734, 80.9%0, 0.0%8, 19.0%42(3) 201362, 82.6%6, 8.0%7, 9.3%75Total154726187DF4Chi-Square8.3Asymptotic Pr> ChiSq0.08Exact Pr ≥ ChiSq0.07 When further analysis was carried out, period 1 and 2 were added together and compared to period 3. When all positives and negatives were compared, there was no statistical difference between the periods. However in the equivocal category, Period 1 and 2 were statistically different than period 3. In fact the only change in period 3 was the increase in the equivocal cases (same case-equivocal IHC and FISH). Conclusion: In the 2013 CAP guidelines, 2+ IHC now includes incomplete staining in >10% of cells. This does not result in more positive cases as was the intention but an increase in the equivocal category by 8.19%. This adds to clinical uncertainty as to how to treat this group of patients. A send out for FISH is labor intensive, slow and costs on average of $650/case. With over 250,000 new cases expected this year in the U.S. this cost exceeds $13million. From all our data, the best parameters for IHC testing would be; positive-strong, complete staining in >10% cells and equivocal to eliminate the incomplete staining category. This would yield the highest number of true positives by FISH and almost eliminate ultimate equivocal cases. Citation Format: Sharma A, Vadehra D, Talal K, Hegde P, Wu R, Tannenbaum S. Value-based medicine: Are the 2013 guidelines for HER2 testing clinically significant and cost effective? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD7-02.
e18294 Background: Revised guidelines for HER-2 testing in Breast Cancer Specimens occurred in 2007 and again in 2013 with an intention to capture more patients who could benefit from HER-2 directed therapy. Methods: The purpose of this study was to compare the HER 2 + cases outright and the equivocal cases that resulted in a reflex FISH test that was ultimately positive utilizing both guidelines. The number of equivocal tests results and those that ultimately were positive, negative or remained equivocal were quantitated. A retrospective analysis on specimens from 2003-2008 and 2013-2016 was performed. Results: see table. Conclusions: An expansion of 8.8% is seen in the equivocal category after adoption of the 2013 guidelines. Despite an increased number of reflex FISH testing there was no significant increase in the number of FISH positive patients. The end result was a greater delay in time to treat patients appropriately for send-out FISH tests and significant increase in costs for testing that did not result in management change. If the additional costs are multiplied by the number of patients with breast cancer each year and resultant equivocal results calculated for the almost 9% increase, that extra cost is close to 12 million dollars. Based on our small institution study, reconsideration of guideline criteria is important in this era of value-based medicine. [Table: see text]
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