Longevity
Tovecimig plus paclitaxel lifted response rates in biliary tract cancer, but survival gain did not follow
By Life and Health Today Staff, . Life and Health Today.
What the trial set out to test
Biliary tract cancers, which arise in the bile ducts and gallbladder, are aggressive and difficult to treat once they have spread. Median overall survival in patients with advanced disease runs to about 12 months, according to MedPage Today's coverage of the COMPANION-002 trial results, presented at the European Society for Medical Oncology annual congress in Madrid and simultaneously published in the Journal of Clinical Oncology.
The trial tested tovecimig, an investigational bispecific antibody, meaning a laboratory-engineered protein designed to block two targets at once. Tovecimig targets VEGF-A and DLL4, two proteins involved in the growth of blood vessels that tumors rely on. It was combined with paclitaxel, a standard chemotherapy drug, in patients who had already received one prior round of treatment with gemcitabine and cisplatin.
What the trial found
Among 168 patients randomized in a 2-to-1 ratio to either the combination or paclitaxel alone, 18.0% of patients receiving tovecimig plus paclitaxel had a measurable tumor response, compared with 5.3% on paclitaxel alone, a statistically significant difference (P=0.0228), reported Nilofer S. Azad, MD, of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore.
Progression-free survival, the length of time before the disease worsened, was 4.7 months in the combination group versus 2.6 months with chemotherapy alone. The hazard ratio of 0.44 means the risk of progression was more than halved at any given point in time during the trial (95% confidence interval 0.30 to 0.66, P less than 0.0001).
Overall survival told a different story: 8.9 months with the combination versus 9.4 months with paclitaxel alone, a difference that was not statistically significant (hazard ratio 1.05, 95% CI 0.7 to 1.5, P=0.77). Azad suggested the trial's crossover design, which allowed patients on paclitaxel alone to switch to the combination once their disease progressed, may have muddied the survival comparison. Among the 57 patients originally assigned to paclitaxel, 54% crossed over, and those who did had a median overall survival of 12.8 months, compared with 6.1 months among the 26 who did not cross over (hazard ratio 0.54, 95% CI 0.3 to 0.98, P=0.04).
What the safety data showed
The most common side effects in the combination arm were hypertension, affecting 69.4% of patients, and fatigue, affecting 66.7%. Grade 3 or higher adverse events, meaning serious or severe, occurred in 93.5% of patients on the combination versus 64.2% on paclitaxel alone. There were six fatal adverse events in the combination arm, including two deaths considered treatment-related, from septic shock and from renal failure combined with sepsis. One fatal adverse event occurred in the paclitaxel-alone arm.
What experts made of it
Azad described the combination as "a promising new strategy for patients with biliary tract cancer," according to MedPage Today.
Sebastián Mondaca, MD, MBA, of the Pontificia Universidad Católica de Chile in Santiago, who served as the invited discussant at the ESMO congress, called the results encouraging given the mechanism and the limited options currently available in this setting. He was less certain about practice change, telling the congress that a phase III trial comparing the combination against FOLFOX (fluorouracil, leucovorin, and oxaliplatin), a different chemotherapy regimen, and demonstrating a clear overall survival benefit, would be the stronger basis for guideline adoption. He added that given the high unmet need, a formal review by a guideline committee was warranted.
Tovecimig is not approved by the US Food and Drug Administration. It remains investigational, meaning it is available only in clinical trials and has not been cleared for standard clinical use.
For patients with advanced biliary tract cancer and their physicians, the trial adds a combination with measurable activity at the second-line stage, though whether that activity translates into longer lives remains an open question that a larger, survival-powered trial would need to answer.
Source: https://www.medpagetoday.com/meetingcoverage/esmo/123567
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