What are the different biological treatments (biologicals) available for an adult patient with a confirmed cancer diagnosis?

Biological Therapies for Cancer

The primary biological treatments for cancer include immune checkpoint inhibitors (anti-PD-1/PD-L1 and anti-CTLA-4 antibodies), monoclonal antibodies targeting specific tumor antigens or growth pathways (anti-EGFR, anti-HER2, anti-VEGF), CAR-T cell therapy, cancer vaccines, and cytokines, with selection based on cancer type, molecular characteristics, and disease stage. 1, 2

Immune Checkpoint Inhibitors

These represent the most significant advancement in cancer immunotherapy and are now standard treatments across multiple malignancies:

• Anti-PD-1 antibodies (nivolumab, pembrolizumab) are FDA-approved for melanoma, non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, head and neck squamous cell carcinoma, urothelial carcinoma, microsatellite instability-high colorectal cancer, hepatocellular carcinoma, and esophageal cancer 1

• Anti-CTLA-4 antibodies (ipilimumab) are used as monotherapy or in combination with anti-PD-1 agents for melanoma (category 1 recommendation), non-small cell lung cancer, renal cell carcinoma, malignant pleural mesothelioma, hepatocellular carcinoma, colorectal cancer, and esophageal cancer 2, 1

• Combination ipilimumab plus nivolumab shows superior efficacy in melanoma and is preferred for patients with low-volume, asymptomatic metastatic disease where time exists for immune response development 2, 1

• Close monitoring for immune-related adverse events is essential, with participation in risk evaluation and mitigation strategy (REMS) programs strongly recommended during ipilimumab treatment 2

Monoclonal Antibodies Targeting Growth Pathways

Anti-EGFR Antibodies

• Cetuximab and panitumumab are effective in metastatic colorectal cancer, but only in patients with RAS wild-type tumors (expanded RAS testing including KRAS exons 2,3,4 and NRAS exons 2,3,4 is mandatory before use) 2

• These agents improve response rates, progression-free survival, and overall survival when combined with FOLFIRI or FOLFOX chemotherapy in first-line treatment of left-sided, RAS wild-type metastatic colorectal cancer 2

• Characteristic skin toxicity requires management with topical corticosteroids and antibiotics 2

• In frail or elderly patients with left-sided, RAS wild-type tumors unable to tolerate chemotherapy, anti-EGFR monotherapy is a reasonable option 2

Anti-VEGF Pathway Agents

• Bevacizumab (anti-VEGF antibody), ramucirumab (anti-VEGFR2 antibody), and aflibercept (VEGF trap protein) demonstrate improved outcomes when combined with chemotherapy in metastatic colorectal cancer and other solid tumors 2

• Bevacizumab is used in metastatic breast cancer, glioblastoma at recurrence, and various other malignancies 2

Anti-HER2 Antibodies

• Trastuzumab and lapatinib are standard treatments for HER2-positive metastatic breast cancer 2

Targeted Therapy for Specific Mutations

• Vemurafenib is a category 1 recommendation for metastatic melanoma with documented BRAF V600 mutations 2

• BRAF-mutant melanoma patients with symptomatic disease or progression despite immunotherapy should receive vemurafenib 2

• Regular dermatologic evaluation is recommended for patients on vemurafenib to monitor for skin complications 2

Cytokine Therapy

• High-dose interleukin-2 remains an option for metastatic melanoma and renal cell carcinoma, though caution is warranted due to high toxicity 2

• Treatment should only occur at institutions with relevant expertise 2

• Contraindications include inadequate organ reserve, poor performance status, and untreated or active brain involvement 2

• Interferon alpha can be used for polycythemia vera-associated pruritus and has cytoreductive properties, though it is poorly tolerated 2

CAR-T Cell Therapy and Cancer Vaccines

• CAR-T cell therapy represents a promising biological treatment with recent trial data showing superiority in clinical outcomes over conventional chemotherapy 3

• Cancer vaccines are emerging as viable treatment options with encouraging results in recent trials 3

• These therapies are increasingly being incorporated into clinical practice, particularly for hematologic malignancies 3

Treatment Selection Algorithm

For melanoma:

• Low-volume, asymptomatic metastatic disease → immunotherapy (ipilimumab or interleukin-2) to allow time for immune response 2
• BRAF-mutant with symptomatic disease or immunotherapy failure → vemurafenib 2
• Resectable stage IV disease → surgery followed by clinical trial enrollment (adjuvant interferon alpha monotherapy is inappropriate) 2

For metastatic colorectal cancer:

• First-line left-sided, RAS wild-type → FOLFIRI or FOLFOX plus cetuximab or panitumumab 2
• RAS mutant or right-sided → chemotherapy plus bevacizumab 2
• MSI-H/dMMR after fluoropyrimidine, oxaliplatin, and irinotecan failure → nivolumab alone or with ipilimumab 1

For non-small cell lung cancer:

• PD-L1 ≥1%, no EGFR/ALK alterations → nivolumab plus ipilimumab first-line 1
• Resectable tumors ≥4 cm or node positive → neoadjuvant nivolumab with platinum-doublet chemotherapy 1

Critical Pitfalls to Avoid

• Never use anti-EGFR antibodies without confirming RAS wild-type status (expanded testing, not just KRAS exon 2) 2

• Do not administer high-dose interleukin-2 or biochemotherapy outside specialized centers 2

• Avoid ipilimumab without establishing immune-related adverse event monitoring protocols 2

• Do not use adjuvant interferon alpha for resected stage IV melanoma outside clinical trials 2

• For suspected lymphoma, avoid corticosteroids before histological confirmation unless neurological status requires it, as steroids cause rapid lymphoma cell disappearance and prevent diagnosis 4