- The update incorporates changes based on a randomized controlled trial of olaparib vs placebo, phase 1 and 2 studies of larotrectinib, and phase 1 and 2 studies of entrectinib.
Why this matters
- The guideline focuses advice on appropriate therapy after disease progression or intolerable toxicity.
- Patients likely to be candidates for post-first-line treatments should be tested during their initial assessment for actionable germline and somatic genomic alterations, including microsatellite instability/mismatch repair deficiency, BRCA mutations, and NTRK gene fusions.
- First-line therapy: Nab-paclitaxel or capecitabine or erlotinib can be added to gemcitabine for patients with either an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or a comorbidity profile that precludes more aggressive regimens, but who wish to receive cancer treatment.
- Proactive dose and schedule adjustments should be made to minimize toxicity.
- In patients with BRCA1/2 germline mutations who undergo first-line platinum-based chemotherapy and have no disease progression for a minimum of 16 weeks, continued treatment options include chemotherapy or olaparib.
- Patients with NTRK fusion-containing tumors should be treated with larotrectinib or entrectinib.
- Among patients who have undergone first-line treatment with a gemcitabine-based regimen, have an ECOG PS of 0-1, a favorable comorbidity profile, and a support system for aggressive medical therapy and can get a chemotherapy port and infusion pump management services, fluorouracil plus nanoliposomal irinotecan, or fluorouracil plus irinotecan if the former is not available, is preferred.
- For patients with ECOG PS 2 or unfavorable comorbidity profile for aggressive regimens, gemcitabine or fluorouracil can be used.
- Nab-paclitaxel can be added to gemcitabine or nanoliposomal irinotecan to fluorouracil, with proactive dose and schedule adjustments to minimize toxicity.