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  Access statistics : Table of Contents
   2018| July-September  | Volume 1 | Issue 1  
    Online since July 31, 2018

 
 
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REVIEW ARTICLES
Pneumonitis after precision oncology therapies: A concise review
Akash Jain, Vickie R Shannon, Ajay Sheshadri
July-September 2018, 1(1):26-37
DOI:10.4103/JIPO.JIPO_9_18  
With greater understanding of the molecular biology of cancer, precision oncology therapies are becoming increasingly prevalent. Adverse events associated with these therapies may cause significant harm to patients if not promptly recognized and treated. In this review, we focus on pneumonitis that occurs as a side effect of treatment with precision oncology agents. We discuss the incidence and time to onset of pneumonitis associated with a broad array of precision oncology agents. We highlight the common patterns of pneumonitis and offer a comprehensive approach to evaluation and treatment with therapy-specific guidelines where available.
  2,642 371 -
ORIGINAL ARTICLES
Erlotinib in patients with advanced non-small cell lung cancer in Middle Eastern population
Abdul Rahman Jazieh, Turki M Fayea, Mervat Mahrous, Tarek Darwish, Essam Fawzi, Ashwaq A Alolayan, Nagham Sheblaq, Mohammed Alkaiyat, Yosra Ali
July-September 2018, 1(1):19-25
DOI:10.4103/JIPO.JIPO_2_18  
Background: Although erlotinib is widely used in the management of non-small cell lung cancer (NSCLC), no prior studies were conducted in Middle Eastern population. Our study aims at evaluating erlotinib prospectively in this population. Patients and Methods: This open-label, prospective, single-arm, multicenter Phase IV clinical trial of erlotinib as single agent evaluated safety and efficacy of Erlotinib in Middle Eastern patients with advanced NSCLC. Results: A total of 56 patients were enrolled in five sites in Saudi Arabia. Majority of patients were males (60%) with median age of 57 years (34–80), Stage IV (98%), and adenocarcinoma (84%). Eastern Cooperative Oncology Group performance Status III (41.1%). Epidermal growth factor receptor (EGFR) mutations were present in 24 patients out of 36 patients tested (67%). The most common reported adverse events (AEs) were rash 36 (64%), diarrhea 29 (52%), fatigue 10 (18%), and anorexia 5 (9%). Grade 4 or 5 AEs were not observed. Complete response was achieved in 2 (3.6%) and overall disease control was 60.8%. Median overall survival (OS) was significantly longer in patients with EGFR mutation than wild type (20 vs. 3 months, P = 0.002). Progression-free survival was 10 months and significantly longer in patients with EGFR mutation than wild type (16 vs. 6 months, P = 0.037). Patients with unknown EGFR status had PSF and OS better than wild-type patients and worse than patients with EGFR mutation. Cox regression analysis showed that older age (P = 0.029, HR 1.064), EGFR wild type (P = 0.014, hazard ratio [HR]: 8.497), and receiving radiation (P = 0.033, HR 6.433) significantly increase risk of death for patients receiving erlotinib. Conclusion: Erlotinib has efficacy and safety profile in Middle Eastern population similar to the reported literature. The empiric use of erlotinib in patients with unknown EGFR status in our patient population is warranted due to high prevalence of the mutation. However, it should not be used in confirmed wild-type disease.
  2,162 178 1
The impact of immune checkpoint inhibitor-related adverse events and their immunosuppressive treatment on patients' outcomes
Hamzah Abu-Sbeih, Tenglong Tang, Faisal Shaukat Ali, Daniel Hartman Johnson, Wei Qiao, Adi Diab, Yinghong Wang
July-September 2018, 1(1):7-18
DOI:10.4103/JIPO.JIPO_12_18  
Background: Immune checkpoint inhibitors (ICPIs) are gaining more popularity as a treatment for advanced cancers. However, immune-related adverse events (irAEs) limit their use. We aimed to assess the impact of irAEs and their treatment on clinical and survival outcomes. Materials and Methods: We retrospectively reviewed records of the patients who received ICPIs between 2011 and 2017. Descriptive analyses were employed to compare different groups. Kaplan–Meier curves and log-rank tests were used to estimate and compare overall survival durations. Results: Of 427 identified patients, 202 (47.3%) had one or more irAEs. Overall, the patients who developed irAEs had better overall survival than did patients with no-irAEs, regardless of immunosuppressant treatment (P < 0.01). Patients with mild irAEs who did not require immunosuppressive treatment had longer overall survival duration than did patients without irAEs (P < 0.01). Patients with three or more irAEs had longer median overall survival compared to patients with two or less irAEs (P = 0.01). Infliximab was associated with shorter duration of steroid use as compared to steroid treatment only (2 months [standard deviation (SD), 8] vs. 4 months [SD, 4]). Steroid treatment for >30 days was associated with higher rate of infections compared to shorter duration (P = 0.03). Conclusion: IrAEs are associated with favorable overall survival, regardless of immunosuppression treatment requirement. IrAEs involving multiple organs appeared to be beneficial for overall survival. Early infliximab use shortens the duration of steroid treatment and therefore balances better cancer outcomes with decreased risk of infection.
  2,007 332 9
Pembrolizumab in advanced gastrointestinal malignancies with defective dna mismatch repair: A case series
David D Stenehjem, Courtney C Cavalieri, Eric Swanson, Benjamin Solomon, Jonathan Whisenant, Dao Tran, John Weis, G Weldon Gilcrease, Sunil Sharma, Ignacio Garrido-Laguna
July-September 2018, 1(1):1-6
DOI:10.4103/JIPO.JIPO_5_18  
Background: Tumors with deficient mismatch repair (dMMR) have a favorable immunological phenotype permitting exploitation by immunotherapies. We aimed to assess our institutional experience of dMMR advanced gastrointestinal (GI) cancers treated with the PD-1 inhibitor pembrolizumab. Materials and Methods: We conducted an observational cohort study of a clinical series of patients with dMMR metastatic GI cancers treated with pembrolizumab from 2015 to 2017. Patients were assessed for best response, time to and reason for discontinuation, and adverse events. Results: A total of 13 patients received at least one dose of pembrolizumab. Median age was 62 years (range 33–74 years). Diagnoses included colorectal (colorectal cancer [CRC], n = 7); extrahepatic and intrahepatic cholangiocarcinoma (EHCC, n = 2; n = 1); pancreatic (pancreatic ductal adenocarcinoma [PDAC], n = 2); and adenocarcinoma of the appendix (n = 1). Five patients received concurrent chemotherapy (FOLFOX or capecitabine) with pembrolizumab (200 mg intravenous [IV] q 2 weeks with FOLFOX or 2 mg/kg IV q 3 weeks with capecitabine). Pembrolizumab was administered 2 mg/kg IV q 3 weeks to all patients who received single-agent treatment. Eleven patients were evaluable for response assessment. Three patients had a complete response (CRC and two EHCC) and one of these patients received concomitant pembrolizumab and FOLFOX. Two patients had a partial response, one with PDAC (−88% per RECIST, continues on treatment after 15.7 months) and the other with CRC (−45% per RECIST, continues after 14.6 months), both patients received concomitant pembrolizumab and FOLFOX and are now maintained on single-agent pembrolizumab. The objective response rate was 42%. Three patients experienced immune-related adverse events requiring discontinuation. Conclusions: This single-institution case series confirms the activity of pembrolizumab in various GI cancers harboring dMMR. Future studies are warranted to determine the role of combinatorial treatment with chemotherapy and/or novel immunotherapies in this population.
  1,777 195 -
REVIEW ARTICLES
Understanding the toxicity of cancer immunotherapies: Use of patient-reported outcomes
Tito R Mendoza
July-September 2018, 1(1):38-45
DOI:10.4103/JIPO.JIPO_10_18  
Immunotherapy has transformed the treatment of various cancers by strengthening suppressed immune systems for antitumor effects. However, altering the immune balance also produces unconventional adverse events (AEs) that are collectively referred to as immune-related AEs. These AEs, which can be thought of as symptomatic toxicities, are typically reported via tabulation of AEs from the National Cancer Institute's Common Terminology Criteria for AEs. These AEs are reported by clinicians. However, it is well known that clinicians' reports of their patients' symptoms are underestimates and in some cases may not be consistent with patients' reports. The symptomatic adverse effects of immunotherapy are best reported by the patients themselves, known as patient-reported outcomes (PROs). This review describes the use of PROs specifically pertaining to symptom burden in cancer patients. The review also discusses challenges in the use of PROs in patients undergoing immunotherapy and provides recommendations for future research.
  1,623 259 -
CASE REPORTS
Bronchiolitis obliterans after combination immunotherapy with pembrolizumab and ipilimumab
Amulya Balagani, Muhammad H Arain, Ajay Sheshadri
July-September 2018, 1(1):49-52
DOI:10.4103/JIPO.JIPO_8_18  
Checkpoint inhibitor therapies are members of a new, groundbreaking class of drugs that reinvigorate the immune system to directly attack tumors. A rare side effect of checkpoint inhibitor therapy is pneumonitis, which typically presents as an interstitial lung disease. In this case report, we present a patient in whom combination therapy with the PD-1 inhibitor pembrolizumab and the CTLA-4 inhibitor ipilimumab induced severe airflow obstruction. This is the first report that shows that checkpoint inhibitors may induce airflow limitation.
  1,267 129 1
Inflammatory colitis after treatment of melanoma with talimogene laherparepvec (T-VEC)
Jennifer Gardner, Teresa Hyun, Gideon Steinbach, John Thompson
July-September 2018, 1(1):46-48
DOI:10.4103/JIPO.JIPO_3_18  
Talimogene laherparepvec (T-VEC) is an intralesional oncolytic viral therapy for the treatment of recurrent, unresectable cutaneous, subcutaneous, and nodal melanoma. It is thought to work through direct tumor oncolysis and by eliciting a tumor-specific systemic immune response. Immune-related adverse events have been reported only rarely with this therapy. We report a case of culture-negative, biopsy-proven colitis following pathologic complete response of recurrent, and intransit cutaneous melanoma to T-VEC. To the best of our knowledge, this is the first report of immune-related colitis following T-VEC.
  1,022 101 -