What is the preferred initial treatment approach, immunotherapy or chemotherapy, for an adult patient with advanced cancer, considering their overall health, cancer type, and stage?

Immunotherapy vs Chemotherapy for Advanced Cancer: Treatment Selection

For most adults with advanced cancer, the choice between immunotherapy and chemotherapy depends critically on cancer type, PD-L1 expression, and performance status, with combination chemoimmunotherapy now the preferred first-line approach for many solid tumors including non-small cell lung cancer.

Cancer Type-Specific Recommendations

Non-Small Cell Lung Cancer (NSCLC)

Squamous Cell Histology:

• For PD-L1 ≥50%: Single-agent immunotherapy (pembrolizumab, cemiplimab, or atezolizumab) is preferred, with 5-year overall survival rates of 18.4% versus 9.7% for chemotherapy alone 1
• For PD-L1 1-49%: Combination pembrolizumab plus platinum-based chemotherapy is strongly recommended, showing 5-year OS rate of 18.4% versus 9.7% with chemotherapy alone (HR 0.71) 1
• For PD-L1 <1%: Chemoimmunotherapy remains preferred over chemotherapy alone, though the benefit is less pronounced 1

Alternative strategies include dual immunotherapy (nivolumab plus ipilimumab) or nivolumab plus ipilimumab with 2 cycles of chemotherapy, particularly in patients with high tumor burden requiring rapid response 1, 2

Non-Squamous Histology:

• Combination approaches with platinum-pemetrexed plus pembrolizumab are standard across PD-L1 expression levels 1
• Bevacizumab should not be routinely added to pemetrexed-platinum therapy due to lack of survival benefit and increased toxicity 1

Hematologic Malignancies

For follicular lymphoma and mantle cell lymphoma:

• Immunochemotherapy (rituximab combined with chemotherapy such as R-CHOP, R-bendamustine, or R-CVP) is the standard approach, not immunotherapy alone 1
• Single-agent rituximab achieves only ~70% response rate with 2-4 year duration, reserved for patients who cannot tolerate chemotherapy 1
• Observation remains appropriate for asymptomatic advanced-stage follicular lymphoma to defer chemotherapy toxicity by median 2-3 years 1

Gynecologic Cancers

For ovarian, uterine serous, and carcinosarcomas:

• Platinum-taxane chemotherapy remains the backbone of treatment 1
• For carcinosarcomas specifically, ifosfamide/paclitaxel is category 1 recommendation with median OS of 13.5 months versus 8.4 months with ifosfamide alone 1
• Immunotherapy is not currently standard for these histologies 1

Performance Status and Patient Selection

Critical exclusion criteria for aggressive therapy:

• ECOG performance status ≥3 or Karnofsky score ≤50 indicates patients should receive best supportive care rather than chemotherapy or immunotherapy 1
• Patients with weeks-to-days life expectancy should not receive anticancer therapy but intensive palliative care focusing on symptom control 1, 3
• Patients with months-to-weeks life expectancy should consider discontinuing anticancer treatment and transition to hospice 1, 3

For patients with adequate performance status:

• Life expectancy measured in months-to-years supports palliative chemotherapy or immunotherapy, which can extend median survival from 3-4 months (best supportive care) to 7-10 months in appropriately selected patients 3
• The focus must shift from life prolongation to quality of life maintenance when performance status progressively declines 3

Second-Line Therapy Considerations

After first-line immunotherapy failure:

• Patients who received single-agent immunotherapy should receive histology-specific platinum-based chemotherapy 1
• For patients who never received checkpoint inhibitors, nivolumab, atezolizumab, or pembrolizumab show clear benefits over docetaxel 1, 2

After first-line chemotherapy:

• Checkpoint inhibitor therapy is preferred if not previously received 1
• Docetaxel with or without bevacizumab, or pemetrexed for non-squamous histology, are alternatives 1

Common Pitfalls to Avoid

Never smokers and light smokers: Chemoimmunotherapy may be preferable to immunotherapy alone due to consistently lower hazard ratios for monotherapy immunotherapy in never smokers 1

High disease burden: When rapid tumor response is needed for symptomatic relief, chemoimmunotherapy produces higher response rates than immunotherapy alone 1

Drug reactions: Platinum agents, taxanes, and checkpoint inhibitors all carry significant allergic reaction risks; desensitization protocols should be available, with ~90% of patients successfully desensitized 1

Bevacizumab contraindications: Squamous histology, hemoptysis, bulky mediastinal disease, and uncontrolled hypertension preclude bevacizumab use 1