ABSTRACT
BACKGROUND: PDL-1 inhibitors have emerged as the new standard of care for second line treatment of NSCLC. METHODS: Eligible patients included, histologically proven NSCLC, ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1 or 2, age 18 years and above, availability of pre-treatment tumor specimen, adequate end organ function, at least one prior platinum-based therapy. Patients who received a minimum of 6 doses of nivolumab were eligible. RESULTS: Eleven previously treated patients with chemotherapy, started on nivolumab from April of 2016 to December of 2018, were retrospectively studied and analysed. The median age of patients was 58 years. Eight (72.73%) of the eleven patients were male. Seven (63.64%) of the patients were current or former smokers. Majority of patients had non-squamous histology; seven (63.64%) adenocarcinoma and four (36.36%) squamous cell carcinoma. 5 (45.46%) of the patients received one prior therapy, three (27.27%) received two prior therapies, and three (27.27%) received three prior therapies. Four (36.36%) of the patients had brain metastasis. Two (18.18%) of the patients were more than 70 years of age. Median number of cycles of nivolumab administered were 10 (range, 6 to 21). At the time of analysis, the median PFS was 8 months (95% CI, 1.52-14.47) and median OS was 15 months (95% CI, 6.9-23.09). Treatment was well tolerated and generally side effects were grade 1 and grade 2, except two patients who develop grade 3/4 pneumonitis. CONCLUSIONS: This is a real-world study of eleven previously treated patients with chemotherapy, started on Nivolumab from April of 2016 to December of 2018. Although, our sample size was small, our data supports the use of nivolumab as a new treatment option for patients of stage 4 NSCLC.
ABSTRACT
INTRODUCTION: Checkpoint inhibitors demonstrate very good anticancer effects, and some patients are long-time responders. As our experience to use these drugs increases, we see more and more patients having different kind of side effects which are usually not seen with chemotherapy. We have observed a subset of patients who appear to be "hyper-progressors," with a greatly accelerated rate of tumor growth and clinical deterioration compared to pretherapy, which was also recently reported by Institut Gustave Roussy. MATERIALS AND METHODS: Medical records from all patients (N = 50) prospectively treated in our hospital by anti-PD-1/PD-L1 were analyzed. The tumor growth rate (TGR) prior ("REFERENCE;" REF) and upon ("EXPERIMENTAL"; EXP) anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth. Associations between TGR and overall survival (OS) were computed. RESULTS: Hyperprogressive disease (HPD) was defined as a RECIST progression at the first evaluation and as a ≥2-fold increase of the TGR between the REF and the EXP periods. Of 50 evaluable patients, four patients (8%) were considered as having HPD. At progression, patients with HPD had a higher rate of new lesions. HPD was associated with a worse outcome (OS). CONCLUSION: Hyperprogression was seen in 4 of 50 (8%) of patients, three of which had urothelial cancer and one malignant melanoma, treated with anti-PD-1 or anti-PD-L1 monotherapy. Patients, on immunotherapy, qualifying for hyperprogression had shorted OS. It is important to have a better understanding of hyperprogression on immunotherapy which shall be addressed in the ongoing immunotherapy studies.
ABSTRACT
Adjuvant ovarian suppression, on addition to chemotherapy, reduces the risk of breast cancer in pre-menopausal women after surgery and adjuvant hormonal therapy. Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) showed greater benefit with exemestane in high risk females in comparison to Tamoxifen. Ovarian Function Suppression (OFS) and exemestane became the standard of care, with 30% patients experiencing grade 3 and more side effects. Much higher benefit was seen in high risk group. But there are concerns about incomplete OFS (estrogen escape) with exemestane plus OFS. Updated analysis of TEXT AND SOFT showed better survival benefit with OFS plus Tamoxifen as compared to OFS plus exemestane. Overall survival is a better end point. Should preference be given to Tamoxifen over exemestane? Further research is required to get the final answer.
