New Predictive Test Gains Momentum With 2 Positive Studies in Localized Colon Cancer

Immunoscore®, a host immune response classification tool, has demonstrated the ability to significantly affect treatment decision-making for patients with stage II colon cancer, particularly among those with high-risk disease, according to new findings that were presented virtually during the 2020 ASCO Quality Care Symposium.¹

The results of the study revealed that Immunoscore can improve the value of care by reducing unnecessary adjuvant chemotherapy and providing more precise treatment to individual patients.

“As City of Hope and other health care institutions embark on fulfilling the potential of precision oncology, diagnostic tests such as Immunoscore offer an evidence-based way to refine adjuvant chemotherapy prescription for stage II colon cancer patients,” said lead study author Afsaneh Barzi, MD, PhD.² “This is why I am exploring strategies to improve patient outcomes.”

Additional evidence of the clinical value of Immunoscore was published in the Journal of Clinical Oncology. The in vitro diagnostic test provided key insight into disease recurrence and use of adjuvant chemotherapy among patients with stage III colon cancer.³

In this study, patients with stage III disease and a high Immunoscore were shown to have prolonged survival and the lowest risk of recurrence versus patients with a low Immunoscore. At 3 years, the recurrence-free rates were 56.9% (95% CI, 50.3%-64.4%) in patients with low Immunoscores, 65.9% (95% CI, 60.8%-71.4%) in those with intermediate Immunoscores, and 76.4% (95% CI, 69.3%-84.3%) in those with high Immunoscores (HR for high vs low, 0.48; 95% CI, 0.32-0.71; P = .0003).

Immunoscore provides a comprehensive assessment of lymphocytic infiltration. The test was included in the 2020 ESMO Clinical Practice Guidelines for Diagnosis, Treatment, and Follow-up of Localized Colon Cancer.²

In the stage II colon cancer study, the main goal was to identify how oncologists utilize the information derived from Immunoscore to inform patient care.¹

The study enrolled 25 physicians to represent a range of practice settings, such as academic medical centers, high-volume hospital networks, and private community practices. All physicians had prior experience in treating patients with stage II colon cancer.

The oncologists were presented with 10 patient profiles representing real-life, de-identified stage II colon cancer cases that were submitted for clinical Immunoscore testing. The physicians’ recommendations for adjuvant chemotherapy and frequency of surveillance were assessed via an online survey.

After completing the survey, the physicians observed a 45-minute presentation on the data derived from Immunoscore. With Immunoscore high or low classification assigned to the patients, the physicians were asked to re-evaluate the same cases.

If at least 1 therapeutic modification, such as chemotherapy decision or surveillance intensity change, was made upon the second round of case evaluations, the physician was counted as having been influenced by the Immunoscore assessment.

With a one-sided alpha of 5% and 80% power, the study investigators hypothesized that a 30% change would be considered impactful, whereas a change of 10% or less would not be.

The results showed that 55% of the physicians made a modification to their initial treatment recommendation following the Immunoscore data presentation across 10 patient cases, meeting the primary objective of the study.

A higher rate of change for chemotherapy recommendation was observed compared with the change rate for surveillance. The rates of change were 34% and 21%, respectively.

All but 1 physician changed their initial recommendation for at least 1 case following the presentation of Immunoscore data. Additionally, 92% of physicians made at least 1 change in their preference for adjuvant chemotherapy. When physicians altered their chemotherapy recommendation, they rarely altered their initial surveillance strategy.

Prior to testing and in alignment with real-world practice, patients with lymphovascular invasion, T4 disease, and poor differentiation status were most often recommended for adjuvant chemotherapy. Across specific tumor factors, including lymphovascular invasion, T4 disease, poor differentiation status, inadequate lymph node harvest, microsatellite instable (MSI)/mismatch repair deficient disease, over 70 years of age, and preexisting comorbidities, more physicians elected against adjuvant chemotherapy after the Immunoscore data were revealed compared with before they were available.

These findings confirm the clinical utility of Immunoscore in the stage III colon cancer study.

The study, led by the Society for Immunotherapy of Cancer, evaluated 763 patients with a predefined consensus Immunoscore.³ All patients had stage III colon cancer defined by the American Joint Committee on Cancer and the Union for International Cancer Control Tumor, Node, Metastasis Staging System. Patients were split into 2 cohorts; cohort 1 included patients from Canada and the United States, and cohort 2 included patients from Europe and Asia.

A significant association with prolonged time-to-recurrence (TTR), overall survival, and disease-free survival was also observed among patients with a high Immunoscore (all P < .001).

Moreover, TTR was found to be independent of patient’s sex, T stage, N stage, tumor sidedness, and MSI status.

Patients with low- (HR for chemotherapy vs no chemotherapy, 0.42; 95% CI, 0.25-0.71; P = .0011) and high-risk (HR for chemotherapy vs no chemotherapy, 0.5; 95% CI, 0.33-0.77; P = .0015) disease who had a high Immunoscore were found to have better survival with chemotherapy compared with patients who had a low Immunoscore (P > .12).

“This study shows that a high Immunoscore is significantly associated with prolonged survival in stage III colon cancer,” said lead study author Bernhard Mlecnik, PhD.² “Our findings suggest that patients with a high Immunoscore will benefit the most from chemotherapy in terms of recurrence risk.”

Immunoscore continues to be evaluated in ongoing clinical trials across multiple tumor types to assess its relevance as a prognostic and predictive tool in patients’ response to treatment.

References

1. Barzi A, Poage GM, Catteau A, et al. Impact of immune assessment on patterns of care in stage II colon cancer. J Clin Oncol. 2020;38(suppl 29):295. doi:10.1200/JCO.2020.38.29_suppl.295
2. New data reinforce Immunoscore clinical utility in localized colon cancer. News release. HalioDx. October 20, 2020. Accessed October 23, 2020. https://bit.ly/3kqjhZy
3. Mlecnik B, Bifulco C, Bindea G, et al. Multicenter International Society for Immunotherapy of Cancer study of the consensus Immunoscore for the prediction of survival and response to chemotherapy in stage III colon cancer. Published September 8, 2020. J Clin Oncol. doi:10.1200/JCO.19.03205