May 21, 2019

A roundtable discussion featuring perspectives from Drs Tanios Bekaii-Saab and Alan P Venook on emerging research and cases from their practices.

• Introduction — Indications for and Practical Implementation of Biomarker Analysis for Patients with Metastatic Colorectal Cancer (mCRC)
• • Biomarker assessment for patients with mCRC (0:00)
  • Perspectives on genomic testing platforms used to perform biomarker analysis for mCRC (3:16)
  • Role of rebiopsy and repeat biomarker assessment for patients with progressive mCRC (7:11)
• Biology of mCRC and Role of Tumor Sidedness in First- and Later-Line Decision-Making
• • Implications of RAS testing for selection of therapy (10:22)
  • Tumor sidedness and therapeutic decision-making (13:55)
  • Similarities and differences in the design and primary endpoints of the Phase III CALGB-80405 and FIRE-3 trials evaluating first-line chemotherapy in combination with cetuximab and/or bevacizumab for KRAS wild-type mCRC (18:12)
  • Prognostic and predictive relevance of primary tumor sidedness in patients with RAS wild-type mCRC on the CALGB-80405 and FIRE-3 trials (22:11)
  • Efficacy of EGFR inhibitor- versus bevacizumab-based treatments for left- versus right-sided RAS wild-type mCRC (23:28)
  • Choosing between EGFR inhibitor- and bevacizumab-based treatments as first- and second-line therapy for patients with symptomatic left-sided RAS wild-type mCRC (31:39)
  • Case (Dr Venook): A woman in her thirties with left-sided RAS wild-type mCRC receives first-line FOLFOXIRI (40:14)
  • Therapeutic options for younger patients with left-sided RAS wild-type mCRC and disease progression on first-line FOLFOXIRI (43:58)
  • Case (Dr Bekaii-Saab): A man in his sixties with left-sided RAS wild-type mCRC and disease progression after 2 years of first-line “stop-and-go” FOLFIRI/bevacizumab receives FOLFIRI/panitumumab (45:56)
  • Activity of cetuximab versus panitumumab and practical considerations for use (49:37)
  • Clinical experience with and management of EGFR inhibitor-associated dermatologic toxicities (51:45)
  • Second opinion: Second-line therapy options for patients with left-sided RAS wild-type mCRC and disease progression on first-line FOLFIRI/bevacizumab (55:48)
  • Faculty perspectives on therapeutic algorithms for first- through later-line therapy for left- versus right-sided RAS wild-type mCRC (1:00:43)
• Current and Future Treatment Options for Patients with BRAF Mutations
• • Efficacy of EGFR inhibition in patients with mCRC and atypical (non-V600E) BRAF mutations (1:08:18)
  • Clinical presentation of and prognosis for patients with mCRC and a BRAF V600E tumor mutation (1:12:22)
  • Activity and tolerability of EGFR/MEK/BRAF-inhibitor combinations in patients with mCRC and a BRAF V600E tumor mutation (1:13:59)
  • Importance of BRAF testing in mCRC; strategies for first-line therapy and beyond (1:16:13)
  • Improved tolerability with triplet EGFR/MEK/BRAF-inhibitor combinations in comparison to anti-EGFR monotherapy or doublet combinations (1:19:54)
  • Case (Dr Venook): A woman in her forties with mCRC, a BRAF V600E tumor mutation and rapid disease progression on first-line FOLFOXIRI/bevacizumab attains long-term disease stabilization with encorafenib/binimetinib/panitumumab (1:22:13)
  • Case (Dr Bekaii-Saab): A man in his fifties with mCRC and a BRAF V600E tumor mutation receives second-line encorafenib/binimetinib/cetuximab on a clinical trial (1:23:27)
• Optimal Management of Microsatellite Instability (MSI)-High or DNA Mismatch Repair-Deficient mCRC
• • Assessment of MSI status and tumor mutation burden as predictors of response to immune checkpoint blockade (1:26:47)
  • Sequencing of anti-PD-1/PD-L1 checkpoint inhibitors for MSI-high mCRC (1:33:19)
  • Neoadjuvant ipilimumab with nivolumab for early-stage colon cancer (1:36:39)
  • Activity and tolerability of immune checkpoint inhibitors alone and in combination in patients with MSI-high mCRC (1:37:34)
  • Case (Dr Bekaii-Saab): A woman in her fifties with MSI-high, right-sided mCRC and a RAS mutation receives second-line pembrolizumab (1:42:11)
  • Case (Dr Venook): A woman in her forties with Stage III CRC initially treated with adjuvant FOLFOX experiences disease progression and receives an assessment of MSI-high disease (1:46:37)
  • Perspective on pseudoprogression in patients undergoing immune checkpoint inhibitor therapy (1:48:50)
• HER2 Positivity and Other Potential Biomarkers
• • Biology and epidemiology of mCRC with HER2 amplification/mutation (1:51:16)
  • Activity of and duration of response to dual HER2-targeted therapy in patients with mCRC and HER2 amplification/mutation (1:54:09)
  • Therapeutic options for patients with mCRC and HER2 amplification/mutation (1:55:45)
  • Case (Dr Venook): A man in his fifties with left-sided, RAS wild-type mCRC and HER2 amplification/mutation receives fourth-line trastuzumab/pertuzumab (2:00:13)
  • Case (Dr Bekaii-Saab): A woman in her sixties with left-sided, RAS wild-type mCRC and HER2 amplification/mutation receives third-line trastuzumab/tucatinib on a clinical trial (2:01:57)
  • Activity of tucatinib in patients with mCRC and HER2 amplification/mutation (2:04:40)
  • Optimizing the risk-benefit ratios of systemic therapy options for patients with mCRC (2:07:36)
  • Modulation of the gut microbiome to enhance response to anti-PD-1 immunotherapy; effects of antibiotics on response to immune checkpoint inhibitors (2:11:12)

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