Gastrointestinal cancers witnessed some exciting updates at the ASCO 2023 which have a huge potential of changing the way of treatment. This article provides some of the most interesting abstracts from the same.

Prospect trial

1. Unblinded randomisation was used to assign 1194 eligible patients with locally advanced rectal cancer to either the experimental arm, which received 6 cycles of modified FOLFOX6, or the control arm, which received chemoradiation delivered as 5,040 cGy over 5.5 weeks along with concurrent chemotherapy using either oral capecitabine or intravenous 5-FU. Following chemotherapy, participants in the experimental group were retested.
2.  If tumours regressed by ≥ 20%, then the participants bypassed radiation and underwent rectal surgery with a total mesorectal excision. Participants with suboptimal responses (< 20% tumour regression) received chemoradiation before surgery. This happened in 9% of patients.
3. At a median follow-up of 58 months, the 5-year disease-free survival rate for the experimental arm was 80.8% compared with 78.6% in the 5-FU CRT arm (HR 0.92, 90.2% CI [0.74, 1.14]; stratified noninferiority P = .0051), meeting the criterion for noninferiority. 5-year overall survival was also similar in both arms.
4. The experimental arm experienced more grade 3 adverse events preoperatively (41.0% vs. 22.8% control), but the control arm experienced more grade 3 adverse events postoperatively (39.0% vs. 25.6% experimental).

PRODIGE 23 -7 year update

1. The three-year findings from this study were previously reported. 
2. Patients with locally advanced rectal cancer were randomly assigned to neoadjuvant mFOLFIRINOX chemotherapy followed by preoperative chemoradiotherapy versus the standard-of-care arm (preoperative chemoradiotherapy only).
3. Disease free survival (DFS) rate after 7 years was 67.6% in the neoadjuvant therapy arm compared with 62.5% in the standard-of-care arm. For patients with metastatic relapse, the median overall survival (OS) was 44.4 months in the neoadjuvant arm compared with 39.4 months in the standard-of-care arm.

These benefits at a mature follow-up are reassuring for the wide applicability of this approach. However, it is not possible to ascertain whether the OS benefit is due to only the neoadjuvant approach or because of the triplet therapy in the same.

MORPHEUS-Liver study

1. Tiragolumab is a human anti-TIGIT monoclonal antibody that, when used in conjunction with other immunotherapies such PD-L1 inhibitors, may improve antitumour responses.TIGIT is an immunological checkpoint and coinhibitory receptor that is expressed on regulatory T cells, natural killer cells, and activated T cells.
2. This study is a phase 1b/2, open-label, multicenter, randomised umbrella study that enrolled participants with advanced hepatocellular carcinoma (HCC) who had not yet received prior systemic therapy using atezolizumab/bevacizumab as a backbone.
3. The primary outcome, as measured by the investigator and based on RECIST 1.1 criteria, increased from 11.1% in the atezolizumab/bevacizumab arm to 42.5% in patients who were randomly assigned to the triplet of tiragolumab plus atezolizumab/bevacizumab. The incidence of grade 1/2 immune-mediated rash was higher in the tiragolumab arm.

NORPACT 1 Study

1. The study in resectable pancreatic cancer explored outcomes after four cycles of neoadjuvant FOLFIRINOX followed by restaging and surgery, followed by adjuvant modified FOLFIRINOX for eight cycles vs upfront surgery followed by adjuvant modified FOLFIRINOX for 12 cycles.
2. Neoadjuvant therapy did not improve overall survival. On the contrary, a numerical advantage was observed for upfront surgery, which yielded a median overall survival of 38.5 months as compared with 25.1 months with the neoadjuvant approach (hazard ratio = 1.52; P = .096) in the intention-to-treat analysis.

NeoCol Study

1. This trial randomly assigned 250 patients with locally advanced colon cancer to upfront surgery or neoadjuvant chemotherapy with either 3 cycles of oxaliplatin, capecitabine every 3 weeks (CAPOX) or 4 cycles of oxaliplatin, 5FU every 2 weeks (FOLFOX).
2. In both arms, the 5-year disease-free survival rate exceeded 75% (P = .94), and the overall survival rate exceeded 85% (P = .95) showing no significant benefit of any one approach.

DESTINY-CRC02 trial

1. This study assessed the efficacy and safety of two doses, 5.4 mg/kg and 6.4 mg/kg respectively of T-DXd in 82 patients with HER2-positive unresectable, recurrent or metastatic colorectal cancer.
2. Regardless of RAS mutation status or prior anti-HER2 treatment, antitumour effectiveness was seen.
3. Safety was in line with the known safety profile of T-DXd, and the 5.4 mg/kg dose was preferred, including for pneumonitis and all-grade interstitial lung disease.

To learn more about ASCO highlights, click on the following links:

1. Breast Cancer: Key Highlights from the 2023 ASCO Conference

2. Key ASCO Highlights on Lung Cancer

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Bipinesh Sansar, DM Medical Oncology, Associate Professor Medical Oncology at MPMMCC and HBCH, Varanasi.