Most Read Articles
Pearl Toh, 22 Oct 2020
The combination therapy comprising carfilzomib, cyclophosphamide and dexamethasone (KCd) is effective, with a tolerable safety profile, in an Asian cohort with high-risk multiple myeloma (MM) — thus providing a more economical alternative as a potential upfront regimen in resource-limited settings, according to leading experts during a myeloma education webinar.
Pearl Toh, 21 Sep 2020
Early and sustained treatments with simplified regimen are the key to achieving good asthma control, said experts during a presentation at the ERS 2020 Congress.
4 days ago
Weight suppression appears to result in future onset of eating disorders characterized by dietary restriction or compensatory weight control behaviours, suggesting weight-suppressed women represent an at-risk group that may benefit from selective prevention programmes, a study has found.
Pearl Toh, 3 days ago
Quadrivalent human papillomavirus (HPV) vaccination can substantially reduce the risk of invasive cervical cancer, by up to almost 90 percent in women who were vaccinated early, a large Swedish registry-based study has shown.

Andecaliximab disappoints in gastric cancer

Audrey Abella
15 Feb 2019

The addition of the monoclonal antibody andecaliximab to nivolumab or a chemotherapy regimen (modified FOLFOX6*) did not provide survival benefit in patients with pretreated metastatic or untreated HER2-negative gastric/gastroesophageal (G/GEJ) adenocarcinoma, according to data presented at ASCO GI 2019.

In a phase II study, 144 individuals (mean age 59 years, 69 percent male) with pretreated metastatic G/GEJ were randomized 1:1 to receive nivolumab 3 mg/kg either alone or in combination with andecaliximab 800 mg. Treatment was administered every 2 weeks for 2 years or until progression, toxicity, or withdrawal of consent. [ASCO GI 2019, abstract 75]

There were no significant differences between the monotherapy arm and the combination arm in terms of overall response rate (ORR, 6.9 percent, 95 percent confidence interval [CI], 2.3–15.5 percent vs 11.1 percent, 95 percent CI, 4.9–20.7 percent; p=0.60), progression-free survival (PFS, median, 1.9 vs 1.8 months, hazard ratio [HR], 0.82, 95 percent CI, 0.58–1.15; p=0.23), or overall survival (OS, median, 5.9 vs 7.2 months, HR, 0.81, 95 percent CI, 0.55–1.18; p=0.27).

In a separate phase III trial (GAMMA-1**), 432 participants with untreated HER2-negative G/GEJ adenocarcinoma were randomized 1:1 to receive modified FOLFOX6 with or without andecaliximab on 28-day treatment cycles. Oxaliplatin was administered on days 1 and 15 of each cycle (total of 6 cycles), followed by leucovorin and 5-fluorouracil on days 1 and 15 until disease progression. Andecaliximab 800 mg was infused on days 1 and 15 of each cycle until disease progression. [ASCO GI 2019, abstract 4]

Despite the slightly improved ORR in the andecaliximab-chemotherapy arm vs the chemotherapy only arm (50.5 percent vs 41.1 percent; p=0.049), there was no difference in terms of PFS (median, 7.5 vs 7.1 months, HR, 0.84, 95 percent CI, 0.67–1.04; p=0.10) or OS (median, 12.5 vs 11.8 months, HR, 0.93, 95 percent CI, 0.74–1.18; p=0.56).

Subgroup analysis showed that participants aged ≥65 years had improved median PFS compared with those aged <65 years (8.7 vs 5.6 months, HR, 0.50; p<0.001). Median OS also appeared better with the combination regimen in this subgroup (13.9 vs 10.5 months, HR, 0.64; p=0.029), highlighting the potential of andecaliximab in providing survival benefit in a certain subset of patients, said study author Dr Manish Shah from the Weill Cornell Medicine/New York Presbyterian Hospital in New York, US.

Moreover, a sensitivity analysis that grouped the subjects by quartiles showed that increasing age was associated with an increasing trend for benefit, noted Shah. “Older people did get more treatment, but that is because they were on treatment for [a longer time],” he pointed out. “This is an area of active research [as there might be] something in the immune microenvironment … [of] older people [that may be different from] younger people,” he added.

Andecaliximab inhibits the enzymatic activity of matrix metalloproteinase 9 (MMP9), an important protein that remodels the extracellular matrix involved in the tumour microenvironment, noted Shah. “All gastric cancers express MMP9 and most overexpress it. [Therefore, MMP9] seems to be a good target for gastric cancer.”

Despite the “disappointing” results, given the favourable outcomes observed in the elderly subset, andecaliximab still merits more comprehensive analyses to establish its potential in this setting, Shah pointed out. “There may be a signal here … More research needs to be done to understand some of the subgroups that may benefit [from andecaliximab],” said Shah.

 

Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Doctor - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
Pearl Toh, 22 Oct 2020
The combination therapy comprising carfilzomib, cyclophosphamide and dexamethasone (KCd) is effective, with a tolerable safety profile, in an Asian cohort with high-risk multiple myeloma (MM) — thus providing a more economical alternative as a potential upfront regimen in resource-limited settings, according to leading experts during a myeloma education webinar.
Pearl Toh, 21 Sep 2020
Early and sustained treatments with simplified regimen are the key to achieving good asthma control, said experts during a presentation at the ERS 2020 Congress.
4 days ago
Weight suppression appears to result in future onset of eating disorders characterized by dietary restriction or compensatory weight control behaviours, suggesting weight-suppressed women represent an at-risk group that may benefit from selective prevention programmes, a study has found.
Pearl Toh, 3 days ago
Quadrivalent human papillomavirus (HPV) vaccination can substantially reduce the risk of invasive cervical cancer, by up to almost 90 percent in women who were vaccinated early, a large Swedish registry-based study has shown.