Treatment Options Following First-line Therapy
Recommendation 3.1 (New)
➤ In patients with tumors harboring NTRK fusions, treatment with
larotrectinib or entrectinib is recommended (Moderate recommendation;
EB-B-L).
Recommendation 3.2
➤ PD-1 immune checkpoint inhibitor pembrolizumab is recommended as
second-line therapy for patients who have tested positive for dMMR or
MSI-H (Strong recommendation; EB-B-H).
Recommendation 3.3 (New)
➤ In patients who have a germline BRCA1 or BRCA2 mutation and have
received first-line platinum-based chemotherapy without disease
progression for at least 16 weeks, options for continued treatment
include chemotherapy or PARP inhibitor olaparib (Moderate
recommendation; EB-B-L).
Qualifying Statement. For the group of platinum-sensitive patients included in
recommendation 3.3, the decision to continue treatment with chemotherapy or proceed to
maintenance therapy with olaparib should be based on a discussion between the patient
and the oncologist, including consideration of whether a maximum response and plateau
in response to chemotherapy have been achieved, level of cumulative toxicities associated
with chemotherapy treatment, patient preference, convenience, toxicity, goals of care, cost,
and clinical evidence, including a lack of overall survival benefit demonstrated in the
POLO randomized controlled trial.
Recommendation 3.4
➤ Gemcitabine plus NAB-paclitaxel may be offered as second-line therapy
to patients who meet all of the following criteria: first-line treatment
with FOLFIRINOX, an ECOG PS of 0 to 1, a relatively favorable
comorbidity profile, and patient preference and a support system for
aggressive medical therapy (Moderate recommendation; IC-B-L).
Recommendation 3.5 (Updated)
➤ Fluorouracil plus nanoliposomal irinotecan, or fluorouracil plus
irinotecan where the former combination is unavailable, is preferred as
second-line therapy for patients who meet all of the following criteria:
first-line treatment with a gemcitabine-based regimen, an ECOG PS of
0 to 1, a relatively favorable comorbidity profile, patient preference
and a support system for aggressive medical therapy, and access to
chemotherapy port and infusion pump management services (Moderate
recommendation; IC-B-L).
