Great progress has been made in the field of tumor immunology in the past decade, but optimism about the clinical application of currently available cancer vaccine approaches is based more on surrogate endpoints than on clinical tumor regression. In our cancer vaccine trials of 440 patients, the objective response rate was low (2.6%), and comparable to the results obtained by others. We consider here results in cancer vaccine trials and highlight alternate strategies that mediate cancer regression in preclinical and clinical models.

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Cancer immunotherapy: moving beyond current vaccines.

Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Purpose
The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epidermal growth factor receptor 2 (HER2/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS).

Patients and Methods
In this phase III study, eligible patients with stage IIIB/IV lung adenocarcinoma were screened for EGFR mutations. Mutation-positive patients were stratified by mutation type (exon 19 deletion, L858R, or other) and race (Asian or non-Asian) before two-to-one random assignment to 40 mg afatinib per day or up to six cycles of cisplatin plus pemetrexed chemotherapy at standard doses every 21 days. The primary end point was PFS by independent review. Secondary end points included tumor response, overall survival, adverse events, and patient-reported outcomes (PROs).

Results
A total of 1,269 patients were screened, and 345 were randomly assigned to treatment. Median PFS was 11.1 months for afatinib and 6.9 months for chemotherapy (hazard ratio [HR], 0.58; 95% CI, 0.43 to 0.78; P = .001). Median PFS among those with exon 19 deletions and L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months for chemotherapy (HR, 0.47; 95% CI, 0.34 to 0.65; P = .001). The most common treatmentrelated adverse events were diarrhea, rash/acne, and stomatitis for afatinib and nausea, fatigue, and decreased appetite for chemotherapy. PROs favored afatinib, with better control of cough, dyspnea, and pain.

Conclusion
Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.

Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations

/pdf/nccn-clinical-practice-guidelines-in-oncology-hepatobiliary-1kpacqqvi8.pdf

NCCN clinical practice guidelines in oncology: hepatobiliary cancers.

The use of monoclonal antibodies (mAbs) for cancer therapy has achieved considerable success in recent years. Antibody-drug conjugates are powerful new treatment options for lymphomas and solid tumours, and immunomodulatory antibodies have also recently achieved remarkable clinical success. The development of therapeutic antibodies requires a deep understanding of cancer serology, protein-engineering techniques, mechanisms of action and resistance, and the interplay between the immune system and cancer cells. This Review outlines the fundamental strategies that are required to develop antibody therapies for cancer patients through iterative approaches to target and antibody selection, extending from preclinical studies to human trials.

https://www.nature.com/articles/nrc3236.pdf?proof=t

Antibody therapy of cancer

Background: Superiority of irinotecan (CPT-11) plus cisplatin over etoposide plus cisplatin in small cell lung cancer (SCLC) has recently been demonstrated. This study determines do

Phase I Dose escalation study of carboplatin to a fixed Dose of irinotecan as first-line treatment of small cell lung cancer

Small cell lung cancer is a highly proliferative tumor with the potential of early hematogeneous spread. At the time of first diagnosis more than 80% of patients present with distant metastases. Although response rate to chemotherapy is high with > 50% confirmed objective responses, the majority of patients relapse within several months after first-line chemotherapy. The combination of cisplatin plus etoposide has become standard chemotherapy. In contrast to early stages, equal efficacy of cisplatin and carboplatin in combination with etoposide has been suggested in advanced disease in two randomized trials in the 1990s. Newer agents like the topoisomerase I inhibitors topotecan and irinotecan have been investigated for first line treatment. Two phase III studies demonstrated similar efficacy of topotecan when compared to etoposide. Results of first line therapy with irinotecan are more contradictory. A first trial demonstrated superiority of irinotecan/cisplatin over etoposide/cisplatin in a Japanese population. However, two subsequent North American phase III trials showed equivalent efficacy. Recently a Scandinavian phase III trial found superiority of irinotecan/carboplatin over etoposide/carboplatin. Prophylactic cranial irradiation (PCI) after first line chemotherapy has become standard of care in advanced stages, because a randomized phase III trial of the EORTC demonstrated a survival benefit. Second-line therapy in relapsed disease improves survival. A randomized trial showed similar efficacy of topotecan when compared to anthracyline containing chemotherapy, with an improvement of cancer related symptoms in the topotecan arm.

Controversies in the Treatment of Advanced Stages of Small Cell Lung Cancer

Die Behandlungsmodalitat des primaren Aderhautmelanoms hat bisher keinen direkten Einfluss auf die Uberlebensprognose des Patienten. Durch die Identifizierung signifikanter Prognoseparameter bezuglich des Risikos, Metastasen eines Aderhautmelanoms zu entwickeln, werden neue Behandlungsstrategien erarbeitet mit dem Ziel, die Entstehung von Metastasen zu verhindern. Dabei spielt die Immuntherapie durch die Entwicklung geeigneter Impfstoffe gegen melanomspezifische Tumorantigene eine zunehmende Rolle. Beim bereits metastasierten Aderhautmelanom betrug bis dato die mittlere Uberlebenszeit ca. 5 Monate. In der letzten Zeit konnte durch die intrahepatische Infusion von Fotemustin die mittlere Uberlebenszeit auf 14 Monate bei selektierten Patienten verlangert werden. Neue Therapieprotokolle werden aufgrund von Chemosensitivitatsuntersuchungen aktuell erarbeitet. Des Weiteren werden immuntherapeutische Modalitaten auch in der Behandlung von Metastasen von Aderhautmelanomen untersucht.

AderhautmelanomAdjuvante Therapie bei Hochrisikopatienten und neue Therapieansätze im metastasierten Stadium

First-in-man dose escalation and pharmacokinetic study of CAP7.1, a novel prodrug of etoposide, in adults with refractory solid tumours.

P-974 Treatment of non-small cell lung cancer (NSCLC) patients withthe trifunctional bispecific antibody catumaxomab (removab®) (anti-EpCAM × anti-CD3: Results of a phase I study

Alexander Schmittel

Papers

Phase I Dose escalation study of carboplatin to a fixed Dose of irinotecan as first-line treatment of small cell lung cancer

Controversies in the Treatment of Advanced Stages of Small Cell Lung Cancer

AderhautmelanomAdjuvante Therapie bei Hochrisikopatienten und neue Therapieansätze im metastasierten Stadium

First-in-man dose escalation and pharmacokinetic study of CAP7.1, a novel prodrug of etoposide, in adults with refractory solid tumours.

P-974 Treatment of non-small cell lung cancer (NSCLC) patients withthe trifunctional bispecific antibody catumaxomab (removab®) (anti-EpCAM × anti-CD3: Results of a phase I study