Programmed Cell Death Protein-1 Inhibitor Research Articles

Atypical Response Patterns in Patients Treated With Nivolumab.

OBJECTIVE. The purpose of this study is to assess the frequency of atypical response patterns in oncology patients treated with the programmed cell death protein-1 inhibitor nivolumab. MATERIALS AND METHODS. This retrospective study included 254 patients treated with nivolumab alone or in combination, from January 2013 through August 2017. A blinded reader prospectively assessed treatment response. Among 166 patients (65%) who experienced a clinical benefit (defined as stable disease, partial response, or complete response as the best response), four response patterns were identified: pattern 1 is a decrease or less than 20% increase in the sum of the longest dimension (SLD) without a return to below the nadir, pattern 2 is a 10-19% increase in SLD with a return to below the nadir, pattern 3 is a 20% or greater increase in SLD with a return to below the nadir (classic pseudoprogression), and pattern 4 is the development of new lesions with a decrease in SLD lasting through at least two consecutive scans. Patterns 2, 3, and 4 were defined as atypical response patterns. RESULTS. Of 166 patients who experienced a clinical benefit, pattern 1 was seen in 133 (80%), pattern 2 was seen in 15 (9%), pattern 3 was seen in two (1%), and pattern 4 was seen in 16 (10%) patients. Thus, atypical response patterns were seen in 33 (20%) patients who experienced a clinical benefit, including 25 of 91 (27%) taking nivolumab and ipilimumab combined, six of 46 (13%) taking nivolumab alone, and two of 29 (7%) taking a combination of nivolumab and another chemotherapeutic agent (p = 0.02). CONCLUSION. Although classic pseudoprogression was rare, an atypical response was seen in 20% of patients who experienced a clinical benefit, and a delayed response up to 24 months of therapy may be seen. Radiologists should be aware of these atypical patterns to avoid errors in response assessment.

Isolated ZIC4 Antibodies and Autoimmune Encephalitis in a Microsatellite-Instability-High Metastatic Uterine Carcinosarcoma during Immune Checkpoint Inhibitor Treatment

Paraneoplastic neurological disorders (PNDs) are a group of neurological disorders associated with neoplasm and are relatively rare, accounting for less than 1% of cancer cases. We present the case of a 58-year-old woman who was diagnosed with metastatic uterine carcinosarcoma and received the programmed cell death protein-1 inhibitor Pembrolizumab. The patient developed agitation, hallucinations and short-term memory loss, followed by seizures and progressive unresponsiveness. Intensive care support and ventilation were required. Given the high suspicion for autoimmune encephalitis, paraneoplastic antibody testing was requested that was strongly positive for ZIC4 antibodies solely. The unresponsiveness of our patient after immunosuppressive treatment inferred poor prognosis, and after a few days, the patient died. To the best of our knowledge, this is the first case of PND with multifocal neurologic deficits in a patient with isolated ZIC4 antibodies associated with uterine carcinosarcoma. Immunotherapy has been shown to precipitate underlying autoimmune diseases, leading to a wide variety of neurological symptoms including encephalitis. Our case highlights the importance of evaluating serum/CSF onconeural antibodies in patients presenting with complex neurological symptoms to determine the possibility of paraneoplastic disorder.

Clinical outcomes of African American patients with advanced or metastatic non-small cell lung cancer on Nivolumab in a single community-based cancer center.

African Americans (AA) have the highest incidence and mortality rates with lung cancer. They are diagnosed at an earlier age with more advanced disease. Programmed cell death protein-1 inhibitor, Nivolumab, was approved as a second-line agent after failure of platinum-based therapy for advanced or metastatic non-small cell lung cancer (NSCLC). The original studies leading to the approval of Nivolumab had insufficient AA patients, thus there is still inadequate knowledge on treatment outcomes among AA patients. Our primary study endpoints were to determine the median overall survival, 1-year overall survival rate, median progression-free survival, and 1-year progression-free survival rate of patients with advanced or metastatic non-small cell lung cancer on Nivolumab. Our secondary study endpoints were to determine the overall tumor response rate, median time to response, median duration of response, and incidence of treatment-related adverse events of grade 3 or 4. In this retrospective study, we reviewed the charts of 38 patients, 29 of which were AA, with advanced or metastatic NSCLC who received Nivolumab from March 1, 2015 until November 30, 2017 from a single community-based cancer center and compared our results with historical data. Adenocarcinoma was the most common histology (71%) among all patients. Seven (18%) continued to use Nivolumab while 21 (55%) discontinued the treatment mainly due to progression of the disease. The median overall survival was 21.4months (95% CI 13.5-27.4) and 17.6months (95% CI 11.5-27.6) for all the patients and AA, respectively. Both have statistically significant difference (P < 0.001) compared to the historical studies of Borghaei et al. and Brahmer et al. At 1 year, the overall survival rate was 73% (95% CI 50-86) and 66% (95% CI 40-82) for all patients and AA, respectively. The median progression-free survival was also statistically significant (P < 0.001) between all the patients 6.3months (95% CI 2.8-8), AA 6.0months (95% CI 2.3-8.0), and the said historical studies. The 1-year progression-free survival rate was 23% (95% CI 10-39) and 28% (95% CI 12-47) for all patients and AA, respectively. Overall tumor response rate which includes complete and partial responses was 21% (95% CI 10-37) and 24% (95% CI 10-43) for all patients and AA, respectively. The median time to response was 3 and 2.8months for all patients and AA, respectively. The median duration of response was 3.8 and 4.0months for all patients and AA, respectively. Treatment-related adverse events of grade 3 or 4 were reported in 8 and 10% in all patients and AA, respectively, similar to the rates previously shown. AA patients with advanced or metastatic NSCLC on Nivolumab had increased overall survival and progression-free survival with similar grade 3 or 4 treatment-related adverse events. Providing adequate access to immunotherapy is indispensable to maximize survival benefit for AA patients.

Association between efficacy of immunotherapy and rate of cancer progression at the time of initiation of immunotherapy: An analysis in metastatic non-small cell lung cancer (NSCLC).

e21225Background: Despite improvements in survival with treatment using single agent Programmed Cell Death Protein-1 inhibitors (PD1i) in second and subsequent line setting for metastatic NSCLC, a ...

Programmed cell death protein-1 inhibitors for immunotherapy of advanced nonmelanoma skin cancer: showing early promise.

Programmed cell death protein-1 inhibitors for immunotherapy of advanced nonmelanoma skin cancer: showing early promise.