Ado-trastuzumab Emtansine (Kadcyla)

Number: 0974

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses ado-trastuzumab emtansine (Kadcyla) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification:

Precertification of ado-trastuzumab emtansine (Kadcyla) is required of all Aetna participating providers and members in applicable plan designs. For precertification of ado-trastuzumab emtansine (Kadcyla), call (866) 752-7021, or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

1. Criteria for Initial Approval

   Aetna considers ado-trastuzumab emtansine (Kadcyla) medically necessary for the following indications: 

   1. Breast Cancer

      1. Subsequent treatment of HER2-positive metastatic or recurrent breast cancer or for HER2-positive breast cancer with no response to preoperative systemic therapy when used as a single agent; or
      2. Adjuvant treatment of HER2-positive early breast cancer when used as a single agent;

   2. Non-small Cell Lung Cancer

      Subsequent treatment of non-small cell lung cancer with HER2 (ERBB2) mutations when both of the following criteria are met:

      1. The disease is recurrent, advanced or metastatic; and
      2. The requested medication will be used as a single agent;

   3. Salivary Gland Tumor

      Treatment of recurrent HER2-positive salivary gland tumors as a single agent.

   Aetna considers all other indications as experimental and investigational (for additional information, see Experimental and Investigational and Background sections).  

2. Continuation of Therapy

   Aetna considers continuation of ado-trastuzumab emtansine (Kadcyla) therapy medically necessary in members requesting reauthorization for an indication listed in Section I when there is no evidence of unacceptable toxicity or disease progression while on the current regimen. Adjuvant treatment of breast cancer will be approved for a total of 12 months of therapy.

3. Related Policies

   1. CPB 0313 - Trastuzumab (Herceptin and biosimilars), Trastuzumab and Hyaluronidase-oysk (Herceptin Hylecta).

Dosage and Administration

Ado‐trastuzumab emtansine is available as Kadcyla in lyophilized powder in single-dose vials containing 100 mg or 160 mg per vial. 

The recommended dose of Kadcyla for breast cancer is 3.6 mg/kg given as an intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. The FDA-approved labeling recommends against administering ado-trastuzumab at doses greater than 3.6 mg/kg. The labeling also recommends against substituting ado-trastuzumab for or with trastuzumab.

Source: Genentech, 2022

Experimental and Investigational

Aetna considers ado-trastuzumab emtansine experimental and investigational for the following indications (not an all-inclusive list) because its effectiveness for these indications, other than the ones listed in Section I, has not been established:

• concomitant use with Herceptin (trastuzumab), Tykerb (lapatinib), or Perjeta (pertuzumab)
• colorectal cancer
• HER2-negative breast cancer
• gastric cancer
• hepatobiliary cancers [cholangiocarcinoma, gallbladder cancer, and salivary duct cancer].

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :
Other CPT codes related to the CPB:
96365	Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to 1 hour
96366	each additional hour (List separately in addition to code for primary procedure)
96372	Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular
96401 - 96450	Chemotherapy administration
HCPCS codes covered if selection criteria are met:
J9354	Injection, ado-trastuzumab emtansine, 1 mg
Other HCPCS codes related to the CPB:
J9306	Injection, pertuzumab, 1 mg
J9355	Trastuzumab, 10 mg
ICD-10 codes covered if selection criteria are met:
C07	Malignant neoplasm of parotid gland [HER2 positive]
C08.0 - C08.9	Malignant neoplasm of other and unspecified major salivary glands [HER2 positive]
C34.00 - C34.92	Malignant neoplasm of bronchus and lung [HER2-positive] [non-small cell lung cancer]
C50.011 - C50.929	Malignant neoplasm of breast [HER2 positive] [not covered for HER2 negative Breast cancer]
ICD-10 codes not covered for indications listed in the CPB (not all inclusive):
C16.0 - C16.9	Malignant neoplasm of stomach
C18.0 - C18.9	Malignant neoplasm of colon
C19	Malignant neoplasm of rectosigmoid junction
C20	Malignant neoplasm of rectum
C22.0 - C22.9	Malignant neoplasm of liver and intrahepatic bile ducts
C23	Malignant neoplasm of gallbladder
C24.0	Malignant neoplasm of extrahepatic bile duct

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications

• Metastatic Breast Cancer (MBC)

  Kadcyla, as a single agent, is indicated for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either received prior therapy for metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy.

• Early Breast Cancer (EBC)

  Kadcyla, as a single agent, is indicated for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment.

Compendial Uses

• Single-agent therapy for recurrent or stage IV (M1) HER2-positive breast cancer
• Non-small cell lung cancer with HER2 mutations
• HER2-positive recurrent salivary gland tumors

Trastuzumab emtansine (T-DM1), brand name Kadcyla, is an antibody-drug conjugate incorporating the HER2-targeted anti-tumor properties of trastuzumab with the targeted delivery to HER2 over-expressing cancer cells of an anti-microtubule agent, DM1 (N-methyl-N-[3-mercapto-1-oxopropyl]-l-alanine ester of maytansinol), a maytansine derivative.  The antibody and the cytotoxic agent are conjugated by means of a stable linker (non-reducible thioether linker) MCC (4‐[N‐maleimidomethyl] cyclohexane‐1‐carboxylate). Emtansine refers to the MCCDM1 complex. The antibody trastuzumab, is well characterized recombinant monoclonal antibody product produced by mammalian (Chinese hamster ovary) cells, and small molecule components (DM1 and MCC) are produced by chemical synthesis. As a conjugate, T-DM1's systemic adverse events (AEs) are significantly minimized due to its targeted delivery by trastuzumab to HER2-positive cells. 

Kadcyla carries a black box warning for hepatotoxicity, cardiac toxicity, and embryo-fetal toxicity.

Hepatotoxicity, liver failure and death have occurred in Kadcyla (ado‐trastuzumab emtansine)‐treated patients. Hepatotoxicity in the form of asymptomatic, transient increases in the concentrations of serum transaminases, has been observed. Serious hepatobiliary disorders, including 2 cases of severe drug‐induced liver injury and associated hepatic encephalopathy, have been reported in clinical trials with Kadcyla (ado‐trastuzumab emtansine). Cases of nodular regenerative hyperplasia (NRH) of the liver have been identified from liver biopsies (3 cases out of 884 treated patients). NRH is a rare liver condition characterized by widespread benign transformation of hepatic parenchyma into small regenerative nodules; NRH may lead to non‐cirrhotic portal hypertension.

Kadcyla may lead to reductions in left ventricular ejection fraction (LVEF). Left ventricular dysfunction occurred in 1.8% of patients in the Kadcyla (ado‐trastuzumab emtansine)‐treated group and 3.3% in the Tykerb (lapatinib) plus capecitabine‐treated group.

Exposure to Kadcyla during pregnancy can result in embryo-fetal harm. Kadcyla (ado‐trastuzumab emtansine) should not be used in women who are pregnant or lactating. There are no adequate and well‐controlled studies of Kadcyla (ado-trastuzumab emtansine) in pregnant women and no reproductive and developmental toxicology studies have been conducted with ado‐trastuzumab emtansine. Treatment with Herceptin (trastuzumab) during pregnancy in postmarketing setting has resulted in oligohydraminos, some associated with fatal pulmonary hypoplasia, skeletal abnormalities and neonatal death. DM1, the cytotoxic component of Kadcyla (ado-trastuzumab emtansine), can be expected to cause embryo‐fetal toxicity based on its mechanism of action.

Warnings and precautions include risk of pulmonary toxicity, infusion-related reactions, hemorrhage, thrombocytopenia, and neurotoxicity. For metastatic breast cancer, the most common adverse reactions (25% or more) with Kadcyla were fatigue, nausea, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, increased transaminases, constipation and epistaxis. For early breast cancer, the common adverse reactions (25% or more) with Kadcyla were fatigue, nausea, increased transaminases, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, peripheral neuropathy, and arthralgia.

Breast Cancer

Kadcyla (ado‐trastuzumab emtansine) is indicated as a single agent for the treatment of patients with HER2‐positive metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have received prior therapy for metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy.

Phase I and II clinical trials of T-DM1 as a single agent and in combination with paclitaxel, docetaxel and pertuzumab have shown clinical activity and a favorable safety profile in patients with HER2-positive MBC.  Two randomized phase III trials of T-DM1 are awaiting final results; the EMILIA trial is evaluating T-DM1 compared with lapatinib plus capecitabine.  The MARIANNE trial is evaluating T-DM1 plus placebo versus T-DM1 plus pertuzumab versus trastuzumab plus a taxane (Barginear et al, 2013).

Mathew and Perez (2011) reviewed the clinical data of T-DM1 in terms of safety and effectiveness, and described ongoing and future trials evaluating its potential role in the management of patients with HER2-positive MBC.  Phase I and II studies showed that the maximum tolerated dose, and thus the recommended dose for T-DM1, is 3.6  mg/kg body weight given intravenously every 3 weeks.  Single-arm phase Ib/II, II and a randomized phase II first-line study of T-DM1 versus the combination of trastuzumab plus docetaxel all showed improved tolerability, and at least equivalent efficacy, compared with the current standard of care.  Two randomized phase III registration studies are now active, evaluating this agent in the refractory and first-line HER2-positive settings.  The authors concluded that T-DM1 has been shown to be a very promising agent for the targeted delivery of chemotherapy and anti-HER2 monoclonal antibody therapy for patients with HER2-positive MBC. 

Burris and colleagues (2011) reported the findings of a single-arm phase II study that assessed safety and effectiveness of intravenous T-DM1 (3.6 mg/kg every 3 weeks) in patients with HER2-positive MBC who had tumor progression after prior treatment with HER2-directed therapy and who had received prior chemotherapy.  With a follow-up of greater than or equal to 12 months among 112 treated patients, the ORR by independent assessment was 25.9 % (95 % CI: 18.4 % to 34.4 %).  Median duration of response was not reached as a result of insufficient events (lower limit of 95 % CI: 6.2 months), and median PFS time was 4.6 months (95 % CI: 3.9 to 8.6 months).  The response rates were higher among patients with confirmed HER2-positive tumors (immunohistochemistry 3+ or FISH-positive) by retrospective central testing (n = 74).  Higher response rates were also observed in patients whose tumors expressed greater than or equal to median HER2 levels by quantitative reverse transcriptase PCR for HER2 expression, compared with patients who had less than median HER2 levels.  T-DM1 was well-tolerated with no dose-limiting cardiotoxicity.  Most adverse events (AEs) were grade 1 or 2; the most frequent grade greater than or equal to 3 AEs were hypokalemia (8.9 %), thrombocytopenia (8.0 %), and fatigue (4.5 %).  The authors concluded that T-DM1 has robust single-agent activity in patients with heavily pre-treated, HER2-positive MBC and is well-tolerated at the recommended phase II dose.

In a single-arm phase II study, Krop et al (2012) examined if T-DM1 is effective in patients with HER2-positive MBC who have previously received all standard HER2-directed therapies.  T-DM1 3.6 mg/kg was administered intravenously every 3 weeks to patients with HER2-positive MBC who had prior treatment with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine.  The primary objectives were ORR by independent review and safety.  Among 110 pre-treated patients (median, 7 prior agents for MBC; median follow-up, 17.4 months), the ORR was 34.5 % (95 % CI: 26.1 % to 43.9 %), clinical benefit rate was 48.2 % (95 % CI: 38.8 % to 57.9 %), median PFS was 6.9 months (95 % CI: 4.2 to 8.4 months), and median duration of response was 7.2 months (95 % CI: 4.6 months to not estimable).  In patients with confirmed HER2-positive tumors (n = 80 by retrospective central testing), the response rate was 41.3 % (95 % CI: 30.4 % to 52.8 %), and median PFS was 7.3 months (95 % CI: 4.6 to 12.3 months).  Most AEs were grades 1 to 2; the most frequent grade greater than or equal to 3 events were thrombocytopenia (9.1 %), fatigue (4.5 %), and cellulitis (3.6 %).  The authors concluded that T-DM1 is well-tolerated and has single-agent activity in patients with HER2-positive MBC who have previously received both approved HER2-directed therapies and multiple chemotherapeutic agents.

Verma and colleagues (2012) randomly assigned patients with HER2-positive advanced breast cancer, who had previously been treated with trastuzumab and a taxane, to T-DM1 or lapatinib plus capecitabine.  The primary end points were PFS (as assessed by independent review), OS, and safety.  Secondary end points included PFS (investigator-assessed), the ORR, and the time to symptom progression.  Two interim analyses of OS were conducted.  Among 991 randomly assigned patients, median PFS as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine (hazard ratio for progression or death from any cause, 0.65; 95 % CI: 0.55 to 0.77; p < 0.001), and median OS at the second interim analysis crossed the stopping boundary for efficacy (30.9 months versus 25.1 months; hazard ratio for death from any cause, 0.68; 95 % CI: 0.55 to 0.85; p < 0.001).  The ORR was higher with T-DM1 (43.6 %, versus 30.8 % with lapatinib plus capecitabine; p < 0.001); results for all additional secondary end points favored T-DM1.  Rates of grade 3 or 4 AEs were higher with lapatinib plus capecitabine than with T-DM1 (57 % versus 41 %).  The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1, whereas the incidences of diarrhea, nausea, vomiting, and palmar-plantar erythrodysesthesia were higher with lapatinib plus capecitabine.  The authors concluded that T-DM1 significantly prolonged PFS and OS with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane.

In a phase II clinical trial, Hurvitz et al (2013) compared the effects of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with HER 2-positive MBC.  Patients (n = 137) with HER2-positive MBC or recurrent locally advanced breast cancer were randomly assigned to trastuzumab plus docetaxel (HT; n = 70) or T-DM1 (n = 67) as first-line treatment until disease progression or unacceptable toxicity.  Primary end points were investigator-assessed PFS and safety.  Key secondary end points included OS, ORR, duration of objective response, clinical benefit rate, and quality of life.  Median PFS was 9.2 months with HT and 14.2 months with T-DM1 (hazard ratio, 0.59; 95 % CI: 0.36 to 0.97); median follow-up was approximately 14 months in both arms.  Objective response rate was 58.0 % (95 % CI: 45.5 % to 69.2 %) with HT and 64.2 % (95 % CI: 51.8 % to 74.8 %) with T-DM1.  T-DM1 had a favorable safety profile versus HT, with fewer grade greater than or equal to 3 AEs (46.4 % versus 90.9 %), AEs leading to treatment discontinuations (7.2 % versus 40.9 %), and serious AEs (20.3 % versus 25.8 %).  Preliminary OS results were similar between treatment arms; median follow-up was approximately 23 months in both arms.  The authors concluded that in this randomized phase II study, first-line treatment with T-DM1 for patients with HER2-positive MBC provided a significant improvement in PFS, with a favorable safety profile, versus HT.

On February 22, 2013, the FDA approved ado-trastuzumab emtansine (Kadcyla) for the treatment of patients with HER2-positive MBC and who were previously treated with trastuzumab and taxanes.  Referred to as T-DM1 during clinical research, Kadcyla was reviewed under the FDA’s priority review program, which provides for an expedited 6-month review of drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products.  Other FDA-approved drugs used to treat HER2-positive breast cancer include trastuzumab (1998), lapatinib (2007) and pertuzumab (2012).  The safety and effectiveness of Kadcyla were evaluated in a clinical study of 991 patients randomly assigned to receive Kadcyla or lapatinib plus capecitabine.  Patients received treatment until either the cancer progressed or the AEs became intolerable.  The study was designed to measure PFS and OS.  Results showed that patients treated with Kadcyla had a median PFS of 9.6 months compared to 6.4 months in patients treated with lapatinib plus capecitabine.  The median OS was 30.9 months in the Kadcyla group and 25.1 months in the lapatinib plus capecitabine group.  The most common AEs reported in patients treated with Kadcyla were constipation, fatigue, headache, elevated levels of liver enzymes, nausea, pain in the muscles or joints, and thrombocytopenia.  Kadcyla is being approved with a “Boxed Warning” alerting patients and health care professionals that the drug can cause liver toxicity, heart toxicity and death.  The drug can also cause severe life-threatening birth defects, and pregnancy status should be verified prior to starting Kadcyla treatment.

Central Nervous System (CNS) Metastases from HER2-Positive Breast Cancer

Askoxylakis and associates (2015) stated that CNS metastases represent a major problem in the treatment of HER2-positive breast cancer because of the disappointing efficacy of HER2-targeted therapies against brain lesions.  The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) has shown efficacy in trastuzumab-resistant systemic breast cancer.  These researchers tested the hypothesis that T-DM1 could overcome trastuzumab resistance in murine models of brain metastases.  They treated female nude mice bearing BT474 or MDA-MB-361 brain metastases (n = 9 to 11 per group) or cancer cells grown in organotypic brain slice cultures with trastuzumab or T-DM1 at equivalent or equipotent doses.  Using intra-vital imaging, molecular techniques and histological analysis these investigators determined tumor growth, mouse survival, cancer cell apoptosis and proliferation, tumor drug distribution, and HER2 signaling.  Data were analyzed with 1-way analysis of variance (ANOVA), Kaplan-Meier analysis, and coefficient of determination.  All statistical tests were 2-sided.  T-DM1 delayed the growth of HER2-positive breast cancer brain metastases compared with trastuzumab.  These findings were consistent between HER2-driven and PI3K-driven tumors.  The activity of T-DM1 resulted in a survival benefit (median survival for BT474 tumors: 28 days for trastuzumab versus 112 days for T-DM1, HR = 6.2, 95 % CI: 6.1 to 85.84, p < 0.001).  No difference in drug distribution or HER2-signaling was revealed between the 2 groups.  However, T-DM1 led to a statistically significant increase in tumor cell apoptosis (1-way ANOVA for ApopTag, p < 0.001), which was associated with mitotic catastrophe.  The authors concluded that T-DM1 can overcame resistance to trastuzumab therapy in HER2-driven or PI3K-driven breast cancer brain lesions due to the cytotoxicity of the DM1 component.  They stated that clinical investigation of T-DM1 for patients with CNS metastases from HER2-positive breast cancer is warranted.

Residual Invasive HER2-Positive Breast Cancer

von Minckwitz and colleagues (2018) noted that patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer.  Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1) provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy.  These researchers carried out a phase-III, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab.  Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles.  The primary end-point was invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral loco-regional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause).  At the interim analysis, among 1,486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2 %) and 165 patients in the trastuzumab group (22.2 %).  The estimated percentage of patients who were free of invasive disease at 3 years was 88.3 % in the T-DM1 group and 77.0 % in the trastuzumab group.  Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio [HR] for invasive disease or death, 0.50; 95 % confidence interval [CI]: 0.39 to 0.64; p < 0.001).  Distant recurrence as the 1st invasive-disease event occurred in 10.5 % of patients in the T-DM1 group and 15.9 % of those in the trastuzumab group.  The safety data were consistent with the known safety profile of T-DM1, with more adverse events (AEs) associated with T-DM1 than with trastuzumab alone.  The authors concluded that among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50 % lower with adjuvant T-DM1 than with trastuzumab alone.

Salivary Duct Cancer

Correa and colleagues (2018) stated that patients with salivary duct cancer (SDC) and HER2 over-expression could receive trastuzumab in combination with chemotherapy for metastatic disease.  No standard treatment exists for patients with HER2-positive metastatic SDC after progression.  These investigators reported an excellent patient response to 2nd-line treatment with ado-trastuzumab emtansine (T-DM1) after progression on paclitaxel plus trastuzumab.  In June 2014, a 79-year old man underwent right parotidectomy and ipsilateral radical neck dissection after the diagnosis of parotid carcinoma.  Pathological staging demonstrated locally advanced disease with the involvement of 13 lymph nodes (levels I, II, III, and IV), with extra-capsular extravasation.  He underwent adjuvant radiotherapy ending in December 2014.  A PET scan in March 2015 diagnosed recurrent and systemic disease, with bone lesions, neck lymph node involvement, and hepatic metastasis.  The immunohistochemistry showed HER2 receptor over-expression (+3/+3).  The patient received 1st-line trastuzumab plus paclitaxel beginning in April 2015.  After 6 cycles, his response was confirmed by PET scan.  In February 2016, he had symptoms of disease progression, and a PET scan revealed disease progression in the neck, bones, and liver.  He started T-DM1 in April 2016.  The neck skin lesions disappeared after 6 cycles, with low toxicity; PET scans performed every 3 months showed response in the liver and bone lesions.  The authors concluded reported the case of a patient with SDC treated with T-DM1, with a very good response.  Salivary carcinoma is a rare disease for which no randomized clinical trials are available.  The maintenance of HER2 blockage might be important in this disease.  These preliminary findings need to be further investigated.

Gallbladder Cancer

Lavingia et al (2022) stated that biliary tract cancers are clinically and genetically heterogeneous cancer type with a worst prognosis among gallbladder adenocarcinoma patients.  Systemic therapeutic options for metastatic biliary tract cancers are fewer, and there are limited treatment choices for the patients who progress on 1st line apart from symptomatic treatment.  Therefore, a biomarker-guided personalized treatment approach needs to be examined among biliary tract cancer subtypes.  These investigators described the case of 53-year-old man with human epidermal growth factor receptor 2 (HER2, ERBB2) positive metastatic gallbladder cancer, treated with 1st-line gemcitabine and cisplatin combination-based chemotherapy along with trastuzumab followed by 2nd-line treatment with mFOLFIRINOX.  On progression in 3rd line, treated with single agent ado-trastuzumab emtansine targeting HER2 and got survival benefit of nearly 6 months.  The authors concluded that this was the 1st reported case from India that examined the possibility and impact of ado-trastuzumab emtansine in advanced gallbladder cancer following exhausting standard therapeutic options.  It highlighted the possibility of examining ado-trastuzumab emtansine for treatment resilient, HER2-positive and advanced gallbladder adenocarcinoma.

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References