Highlights on Gastrointestinal Malignancies
Gastrointestinal (GI) malignancies remain a central focus of research and treatment within the oncology community. Colorectal cancer remains the third most common cancer diagnosed in Europe. Experts focuse extensively on new treatments for malignancies across the GI spectrum.
Advances in Gastric Cancer Treatment
The phase II KEYNOTE-059 trial1 found that the immune checkpoint inhibitor pembrolizumab demonstrated relatively strong response rates among heavily pretreated patients with metastatic or recurrent gastric cancer.
The study included a cohort of 259 patients with metastatic disease and at least two previous lines of chemotherapy who were treated with the PD-1 inhibitor pembrolizumab alone, as well as two smaller cohorts of patients with newly diagnosed disease treated with either pembrolizumab in combination with chemotherapy (25 patients) or first-line pembrolizumab alone (31 patients).
In the pretreated group of patients, after a follow-up period of 6 months, there was an objective response rate of 12% with pembrolizumab monotherapy. Patients who expressed PD-L1 fared better, with a response rate of 16%, compared with 6% in those who did not. The median duration of response was 14.2 months, and some experienced durable responses of 19.0 months or longer.
The two newly diagnosed cohorts had objective response rates of 60% (combination therapy) and 26% (monotherapy). The therapy was generally well tolerated across the cohorts.
An update to the phase III study ATTRACTION-022 confirmed survival by nivolumab (n = 330) versus placebo (n = 163) in heavily pretreated mGC (5.3 vs. 4.1 months, HR 0.62, p < 0.0001). Asian patients with resectable progressive gastric carcinoma who were refractory or intolerant to at least two standard therapies were included in this study.
The one-year OS was 27 against 12%. The OS advantage is evident in all PD-L1 expression groups. The objective response rate (ORR) was 12 versus 0% (p <0.0001). Molecular analyzes complement the significance of PD-L1 expression. The data on the efficacy of nivolumab suggest a place for immunotherapy in patients with progressive GC. Additional studies, including first-line and non-Asians, are already in progress.
Trials in Colorectal Cancers
VOLFI3 is the first study comparing FOLFOXIRI (leucovorin/fluorouracil 3.200mg/m2 /oxaliplatin/ irinotecan 165mg/m2, n = 33) versus a combination of mFOLFOXIRI (leucovorin/fluorouracil 3.000mg/m2 /oxaliplatin/irinotecan 150mg/m2) with the monoclonal antibody panitumumab (n = 63) in the first-line treatment of the primary non-resectable metastatic RAS wild-type colorectal carcinoma (mCRC). The ORR, the primary endpoint, was significantly higher in the combination arm and was 85.7 vs. 60.6% (p = 0.0096), which resulted in a very high secondary resection rate (60 vs. 36.4%).
The addition of panitumumab to FOLFOXIRI achieved an impressive improvement in response rates in right (60 vs. 37.5%, p = 0.6372) and left-sided tumors (90.6 vs. 60%, p = 0.021) and in BRAF mutant mCRC (71.4 vs. 22.2%).
Another centerpiece of the GI cancers center on the debate surrounding 3 versus 6 months of adjuvant chemotherapy with FOLFOX or CAPOX regimens for colorectal cancer. Results of the IDEA collaboration4, a collection of six major trials, were presented during the 2017 ASCO Annual Meeting in Chicago.
Although those trials collectively found that 3 months of therapy was, in some cases, almost as effective as the standard 6 months, a pooled analysis of the trials found that 3 months failed to achieve noninferiority to 6 months of treatment, but this result varied by regimen and by disease stage. In general, experts agreed that low-risk patients can receive the shorter course of therapy with CAPOX, whereas higher-risk patients may need 6 months of FOLFOX. Some high-risk patients who are not candidates for CAPOX would still receive FOLFOX, and, in those patients, the IDEA trials show that 6 months is the better option.
One of the primary results of the IDEA trials was a substantially decreased neurotoxicity profile with CAPOX.
- Wainberg Z. et al, KEYNOTE-059 Update: Efficacy and safety of pemprolizumab alone or in combination with chemotherapy in patients with advanced gastric or gastroesophageal (G/GEJ) cancer
- Boku N. et al, A Phase 3 Study of nivolumab (Nivo) in previously treated advanced gastric or gastroesophageal junction (G/GEJ) cancer: Updated results and subset analysis by PD-LD1 expression (ATTRACTION-02)
- Geissler M. et al, mFOLFOXIRI + panitumumab versus FOLFOXIRI as first-line treatment in patients with RAS wild-type metastatic colorectal cancer m(CRC): A randomized phase II VOLFI trial of the AIO (AIO-KRK0109)
- André T. et al, The IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration: Prospective Combined Analysis of Phase III Trials Investigating Duration of Adjuvant Therapy with the FOLFOX (FOLFOX4 or Modified FOLFOX6) or XELOX (3 versus 6 months) Regimen for Patients with Stage III Colon Cancer: Trial Design and Current Status