Taking a Look Back at Trials From ASCO GI 2022

Van K. Morris, MD

The 2022 Gastrointestinal Cancers Symposium encompassed more than 650 abstracts across solid tumors. Below, we review some of the most talked about abstracts that were presented at the meeting.

Colorectal Cancer

1. Phase I/II trial of encorafenib, cetuximab, and nivolumab in patients with microsatellite stable, BRAFV600E metastatic colorectal cancer (Abstract 12).¹

The study enrolled patients with microsatellite stable (MSS), BRAF V600E–mutant metastatic colorectal cancer (mCRC) who had received 1 to 2 prior lines of therapy not including a BRAF, MEK, ERK, EGFR, and checkpoint inhibitor.

The results showed that nivolumab (Opdivo) plus encorafenib (Braftovi) and cetuximab (Erbitux) led to an overall response rate (ORR) of 50% (95% CI, 28%-72%) among 22 evaluable patients. All responses were partial; the disease control rate was 96% (95% CI, 77%-100%).

At a median follow-up of 16.3 months (95% CI, 6.9-not applicable [NA]), the median progression-free survival (PFS) was 7.4 months (95% CI, 5.6-NA) and the median overall survival (OS) was 15.1 months (95% CI, 7.7-NA). Additionally, the median duration of response (DOR) was 7.7 months (95% CI, 3.8-NA).

The most common adverse effects (AEs) were headache (n = 17; 65%), nausea (n = 9; 35%), and maculopapular rash (n = 8; 31%). One event each of grade 3 colitis, maculopapular rash, asymptomatic elevated amylase/lipase, and leukocytosis, and grade 4 myositis was reported.

2. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): Final results from a phase 2, multicenter, open-label study (DESTINY-CRC01) (Abstract 119).²

Eligible patients included those with unresectable and/or mCRC with centrally confirmed HER2 expression and wild-type RAS/BRAF V600. Patients must have received at least 2 prior regimens.

Patients were randomized to 1 of 3 cohorts: patients with immunohistochemistry (IHC) 3+ or IHC 2+/in situ hybridization (ISH)+ disease (cohort A; n = 53); patients with IHC 2+/ISH-negative disease (cohort B; n = 15); and patients with IHC 1+ disease (cohort C; n = 18).

At a median follow-up of 62.4 weeks, patients in cohort A had an ORR of 45.3% (95% CI, 31.6%-59.6%), a median DOR of 7.0 months (95% CI, 5.8-9.5), a median PFS of 6.9 months (95% CI, 4.1-8.7), and a median OS of 15.5 months (95% CI, 8.8-20.8).

No responses were seen in cohorts B and C.

The safety profile was consistent with that of the primary analysis. Low-grade gastrointestinal and hematologic AEs were most common. Interstitial lung disease/pneumonitis occurred in 9.3% (n = 8) of patients; 3.5% of cases were grade 5.

3. A phase II study of pembrolizumab, binimetinib, and bevacizumab in patients with microsatellite-stable, refractory, metastatic colorectal cancer (mCRC) (Abstract 118).³

The study included patients with mCRC whose disease progressed on at least 2 prior lines of therapy.

Primary results indicated that pembrolizumab (Keytruda) plus binimetinib (Mektovi) and bevacizumab (Avastin) elicited a median PFS of 5.8 months (95% CI, 4.2-8.9). Five patients (13%) achieved a partial response, 24 patients (62%) reached stable disease and 29 patients (74%) derived clinical benefit at the first re-staging at 2 months.

The most common AEs were rash (n = 40; 85%), diarrhea (n = 28; 60%), and nausea (n = 20; 43%).

Biliary Tract Cancer

4. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1 (Abstract 378).⁴

Enrolled patients had locally advanced or metastatic biliary tract cancer. Patients must have been untreated if they presented with unresectable or metastatic disease at diagnosis and disease recurrence within 6 months of curative surgery or adjuvant therapy.

The results demonstrated that durvalumab (Imfinzi) plus gemcitabine and cisplatin led to a 20% reduction in the risk of death vs placebo plus chemotherapy (HR, 0.80; 95% CI, 0.66-0.97; P = 0.021).

At a median follow-up of 13.7 months in the durvalumab/chemotherapy arm and 12.6 months in the placebo/chemotherapy arm, the median OS was 12.8 months (95% CI, 11.1-14) vs 11.5 months (95% CI, 10.1-12.5), respectively. The 18-month OS rates were 35.1% (95% CI, 29.1%-41.2%) vs 25.6% (95% CI, 19.9%-31.7%), respectively. The 24-month OS rates were 24.9% (95% CI, 17.9%-32.5%) vs 10.4% (95% CI, 4.7%-18.8%), respectively.

The median PFS was 7.2 months (95% CI, 6.7-7.4) with durvalumab plus gemcitabine and cisplatin vs 5.7 months (95% CI, 5.6-6.7) with placebo plus gemcitabine and cisplatin (HR, 0.75; 95% CI, 0.64-0.89; P = .001).

The ORR was 26.7% with durvalumab vs 18.7% with placebo.

The most common AEs were anemia (48.2%), neutropenia (31.7%), and nausea (40.2%).

Hepatocellular Carcinoma

5. Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA (Abstract 379).⁵

HIMALAYA enrolled patients with confirmed unresectable and untreated hepatocellular carcinoma (HCC) without portal vein thrombosis. Patients must have had Barcelona Clinic Liver Cancer (BCLC) B disease that was not eligible for locoregional therapy, BCLC C or Child-Pugh A disease.

At data cutoff, durvalumab plus tremelimumab led to a significant improvement in OS vs sorafenib (Nexavar) as frontline therapy in patients with unresectable HCC, meeting the primary end point of the study (HR, 0.78; 96.02% CI, 0.65-0.92; P = .0035).

Additionally, durvalumab demonstrated noninferior OS vs sorafenib (HR, 0.86; 96% CI, 0.73-1.03). The median OS was 16.4 months (95% CI, 14.2-19.6) with durvalumab/tremelimumab, 16.6 months (95% CI, 14.1-19.1) with durvalumab, and 13.8 months (95% CI, 12.3-16.1) with sorafenib.

The 24-month rate was 40.5% with durvalumab/tremelimumab, 39.6% with durvalumab, and 32.6% with sorafenib. The 36-month OS rates were 30.7%, 24.7%, and 20.2%, respectively.

The ORR was 20.1% (n = 79) with durvalumab/tremelimumab, 17.0% (n = 66) with durvalumab alone, and 5.1% (n = 20) with sorafenib alone.

In terms of safety, durvalumab/tremelimumab and durvalumab monotherapy had manageable safety profiles with lower rates of grade 3/4 treatment-related AEs (TRAEs) and TRAEs leading to discontinuation vs sorafenib without any increase in liver toxicity or bleeding risk.

References

1. Morris VK, Parseghian CM, Escano M, et al. Phase I/II trial of encorafenib, cetuximab, and nivolumab in patients with microsatellite stable, BRAFV600E metastatic colorectal cancer. J Clin Oncol. 2022;40(suppl; abstr 12). doi:10.1200/JCO.2022.40.4_suppl.012.
2. Yoshino T, Di Bartolomeo M, Raghav K, et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing metastatic colorectal cancer (mCRC): final results from a phase 2, multicenter, open-label study (DESTINY-CRC01). J Clin Oncol. 2022;40(suppl; abstr 119). doi:10.1200/JCO.2022.40.4_suppl.119.
3. Friedrich T, Blatchford PJ, Lentz RW, et al. A phase II study of pembrolizumab, binimetinib, and bevacizumab in patients with microsatellite-stable, refractory, metastatic colorectal cancer (mCRC). J Clin Oncol. 2022;40(suppl; abstr 118). doi:10.1200/JCO.2022.40.4_suppl.118.
4. Oh DY, He AR, Qin S, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. J Clin Oncol. 2022;40(suppl; abstr 378).doi:10.1200/JCO.2022.40.4_suppl.378.
5. Abou-Alfa G, Chan SL, Kudo M, et al. Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA. J Clin Oncol. 2022;40(suppl; abstr 379). doi:10.1200/JCO.2022.40.4_suppl.379.