INDICATION AND LIMITATIONS OF USE

Vectibix® is indicated for the treatment of adult patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test) metastatic colorectal cancer (mCRC): Read More

Vectibix® is indicated for the treatment of adult patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test) metastatic colorectal cancer (mCRC): Read More

Prescribing Information Indication Important Safety Information Patient Site
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Study

Head-to-head evidence from a phase 3 study demonstrating Vectibix® superiority over Avastin® in WT RAS* left-sided mCRC1

PARADIGM TELLS THE LEFT SIDE STORY

Join Bradley G. Somer, MD, as he explains the relevance of tumor sidedness and molecular biomarkers in the context of data from the phase 3 PARADIGM study, a head-to-head evaluation of Vectibix® vs Avastin® for patients with left-sided, WT RAS* mCRC.

Bradley G. Somer, MD, is a paid consultant for Amgen.

*Defined as wild type in both KRAS and NRAS.

KRAS = Kirsten rat sarcoma viral oncogene homolog; mCRC = metastatic colorectal cancer; NRAS = neuroblastoma RAS viral oncogene homolog; PARADIGM = Pantiumumab and RAS Diagnostically useful Gene Mutation for metastatic colorectal cancer (mCRC); RAS = rat sarcoma viral oncogene homolog; WT = wild type. 

Reference: Vectibix® (panitumumab) prescribing information, Amgen.

Find Registrational Pivotal Trial Data
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First phase 3 study comparison between Vectibix® (panitumumab) and Avastin®

First phase 3 study designed to prospectively compare Vectibix® and Avastin® in combination with mFOLFOX6 for patients with WT RAS * left-sided mCRC1

Head-to-head study

Head-to-head study (N=823) comparing Vectibix® to Avastin® in combination with chemotherapy in Japanese patients with WT RAS * mCRC and left-sided primary tumors1

First prospective study comparing the effects of biologic therapies on patients with left-sided primary tumors

First prospective study comparing the effects of biologic therapies in patients with left-sided primary tumors1

PARADIGM reinforces the value of:

  • Conducting early biomarker testing to determine a patient’s RAS status
  • Including tumor sidedness as a criterion for the selection of biologic therapies
  • Choosing Vectibix® + FOLFOX as 1L therapy in newly diagnosed patients with WT RAS* and left-sided mCRC

*Defined as wild type in both KRAS and NRAS.2

1L = first line; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; mCRC = metastatic colorectal cancer; PARADIGM = Panitumumab and RAS, Diagnostically useful Gene Mutation for metastatic colorectal cancer (mCRC); RAS = rat sarcoma viral oncogene homolog; WT = wild type.

THE EFFICACY OF VECTIBIX® AS 1L THERAPY WAS FIRST ESTABLISHED IN PRIME, A PHASE 3 STUDY2,3

Early targeted therapy with Vectibix® + FOLFOX4 improved survival in newly diagnosed WT RAS* mCRC patients2,3

Results from the post hoc analysis of the WT RAS* subgroup

10.1 months, 7.9 months
10.1 months, 7.9 months
25.8 months, 20.2 months
25.8 months, 20.2 months

There are no OS or PFS benefits in patients with RAS-mutant mCRC treated with Vectibix®2

PRIME PHASE 3 STUDY DESIGN

PRIME was an open label, randomized (1:1), multicenter study of Vectibix® Q2W + FOLFOX4 vs FOLFOX4 Q2W alone in treatment of newly diagnosed mCRC patients. Among the study population of 1,183 patients with previously untreated mCRC, 656 were WT KRAS† patients. The extended RAS population in the post hoc analysis consisted of 512 WT RAS* patients. Of these, 259 received Vectibix® + FOLFOX4 and 253 received FOLFOX4 alone.2,3

*Defined as wild type in both KRAS and NRAS.2

†Exon 2 in codons 12 and 13.1

1L = first line; CI = confidence interval; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; HR = hazard ratio; KRAS = Kirsten rat sarcoma viral oncogene homolog; mCRC = metastatic colorectal cancer; OS = overall survival; PFS = progression-free survival; PRIME = Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy; Q2W = every 2 weeks; RAS = rat sarcoma viral oncogene homolog; WT = wild type.

paradigm:

STUDY DESIGN

Phase 3, randomized, open-label, multicenter study in Japanese patients1

TapClick arrow to see Important Study Considerations

  • Japanese patients with WT RAS† mCRC1
    • Unresectable disease
    • No previous chemotherapy‡
    • Age: 20–79 years
    • ECOG performance status 0–1
    • At least 1 evaluable lesion
    • Adequate organ function
    • Life expectancy ≥ 3 months
    Primary endpoint1
    • OS: left-sided§ and overall population
    Secondary endpoints1
    • PFS, RR, DOR, R0 resection: left-sided§ and overall populations
    • Safety: all treated patients
    Exploratory endpoints1
    • ETS, depth of response, DCR: left-sided§ and overall populations

    *Until disease progression, unacceptable toxicity, withdrawal of consent or investigator’s judgement or curative intent resection.1

    †Defined as wild type in both KRAS and NRAS.2

    ‡Adjuvant fluoropyrimidine monotherapy allowed if completed ≥ 24 weeks before enrollment.

    §Primary tumor in descending colon, sigmoid colon, rectosigmoid, and rectum.1

    DCR = disease control rate; DOR = duration of response; ECOG = Eastern Cooperative Oncology Group; ETS = early tumor shrinkage; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; KRAS = Kirsten rat sarcoma viral oncogene homolog; mCRC = metastatic colorectal cancer; NRAS = neuroblastoma RAS viral oncogene homolog; OS = overall survival; PARADIGM = Panitumumab and RAS, Diagnostically useful Gene Mutation for metastatic colorectal cancer (mCRC); PFS = progression-free survival; R0 = curative resection; RAS = rat sarcoma viral oncogene homolog; RR = response rate; WT = wild type.
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Outcomes

Vectibix® vs Avastin® in combination with mFOLFOX6

  • VECTIBIX® SIGNIFICANTLY INCREASED OVERALL SURVIVAL IN JAPANESE PATIENTS WITH WT RAS* mCRC1

    Primary Endpoint

    18% reduction in the risk of death for patients with left-sided tumors treated with Vectibix® vs Avastin®

    Vectibix® (panitumumab) vs Avastin® + mFOLFOX6: Overall survival in left-sided population graph
    content1-2x-mb

    Vectibix® plus mFOLFOX6 provided a survival benefit vs Avastin® plus mFOLFOX6, reinforcing the clinical value of Vectibix® as a first-line treatment in patients with WT RAS*, left-sided metastatic colorectal cancer.

    *Defined as wild type in both KRAS and NRAS.2
    CI = confidence interval; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; HR = hazard ratio; mCRC = metastatic colorectal cancer; RAS = rat sarcoma viral oncogene homolog; WT = wild type.

  • NO DIFFERENCE IN PFS1

    secondary endpoints

    Vectibix® (panitumumab) vs Avastin® + mFOLFOX6: Progression-free Survival in left sided population graph
    Vectibix® (panitumumab) vs Avastin® + mFOLFOX6: Progression-free Survival in left sided population graph

    Analysis was not powered or adjusted for multiplicity to assess efficacy on this endpoint.

    Patients who underwent curative resection were censored from the PFS analysis on the final day when no progressive disease was confirmed. This censoring could have impacted the PFS results.

    CI = confidence interval; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; HR = hazard ratio; PFS = progression-free survival.

  • RESPONSE RATES, DURATION OF RESPONSE, AND CURATIVE RESECTION RATES1

    secondary endpoints

    Response rate, duration of response, and curative resection rates table
    content3-2x-mb

    Analyses were not powered or adjusted for multiplicity to assess efficacy on these endpoints.

    *DOR was evaluated in patients with complete or partial response.1
    CI = confidence interval; DOR = duration of response; FOLFOX = fluorouracil, leucovorin, and oxaliplatin.

WHAT COULD TUMOR SHRINKAGE BE AT 8 WEEKS?

The PARADIGM Study exploratory endpoints could inform your expectations for patient treatment response. These analyses were not powered to assess efficacy.

  • RATES OF EARLY TUMOR SHRINKAGE AT WEEK 8 COMPARED TO BASELINE1

    Exploratory endpoints

    Early tumor shrinkage in 30% or greater and 20% or greater analyses
    content4-2x-mb

    Analysis was not powered or adjusted for multiplicity to assess efficacy in this endpoint.

    CI = confidence interval; FOLFOX = fluorouracil, leucovorin, and oxaliplatin.

  • CONSIDER ETS DATA FROM PRIME, PEAK, AND PARADIGM

    Exploratory endpoints

    content5-2x
    content5-2x-mb

    *Defined as wild type in both KRAS and NRAS.2

    1L = first line; CI = confidence interval; ETS = early tumor shrinkage; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; KRAS = Kirsten rat sarcoma viral oncogene homolog; mCRC = metastatic colorectal cancer; mo = months; NRAS = neuroblastoma RAS viral oncogene homolog; OS = overall survival; RAS = rat sarcoma viral oncogene homolog;
    WT = wild type.

  • DEPTH OF RESPONSE8

    Exploratory endpoints

    Vectibix® (panitumumab) vs Avastin® + mFOLFOX6: Depth of response in Left-sided population
    Vectibix® (panitumumab) vs Avastin® + mFOLFOX6: Depth of response in Left-sided population

    Depth of response is defined as the best percentage change from baseline in target lesions. Depth of response evaluated in patients with measurable lesions in baseline.

    Horizontal dotted line at ~30% indicates threshold for partial response, a decrease in target lesion size by approximately 30%, as defined by RECIST v1.1.

    Predefined exploratory endpoint. Analysis was not powered or adjusted for multiplicity to assess efficacy.

    FOLOX = fluorouracil, leucovorin, and oxaliplatin; RECIST = Response Evaluation Criteria in Solid Tumors.

  • OVERALL SURVIVAL IN PATIENTS WITH RIGHT-SIDED TUMORS1

    Exploratory endpoints

    Vectibix® (panitumumab) vs Avastin® + mFOLFOX6: Overall survival in Right-sided population
    content7-2x-mb

    Predefined exploratory endpoint. Analysis was not powered or adjusted for multiplicity to assess efficacy.

    FOLFOX = fluorouracil, leucovorin, and oxaliplatin.

Outcomes
  • Investigators modified the primary endpoint after the study began, from overall survival (OS) in all patients to OS in patients with left-sided tumors1
    • This change was based on evidence from at least seven (7) randomized clinical trials suggesting that the benefit of anti-EGFR antibodies combined with chemotherapy is enhanced in patients with left-sided tumors1,9-11
    • The statistical analysis plan was modified to require a
      2-sided P-value of 0.042 as the threshold for statistical significance in the left-sided population1
  • There were no differences between panitumumab and bevacizumab in patients with right-sided tumors1
  • Panitumumab did not differ from bevacizumab on progression-free survival, and survival curves did not separate before 24 months1
    • Other response outcomes were directionally consistent for panitumumab, including response rates, duration of response, curative resection rates, depth of response, and early tumor shrinkage1
    • Similar proportions of patients in each group received subsequent lines of therapy1
    • Fewer panitumumab vs bevacizumab patients received subsequent anti-EGFR treatments1
      • Two separate studies have shown that anti-EGFR treatments may prolong survival in later lines of therapy2,12
  • Although other response outcomes were directionally consistent for panitumumab, the study was not designed to establish statistical significance on these endpoints1

EGFR = epidermal growth factor receptor.

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SAFETY

Most Frequent Adverse Events In PARADIGM8

Adverse events of any grade ≥ 20% in either treatment arm.8

Vectibix® (panitumumab) vs Avastin® + mFOLFOX6: Dermatological toxicity reactions
Vectibix® (panitumumab) vs Avastin® + mFOLFOX6: Dermatological toxicity reactions

Dermatological toxicity reactions occurred predominantly in the Vectibix® arm.1 Prophylactic measures may help reduce the severity of dermatologic toxicities.13 Examples of prophylactic skin treatments can be found here.

PARADIGM = Panitumumab and RAS, Diagnostically useful Gene Mutation for metastatic colorectal cancer (mCRC).

How would you approach treatment?

See the medical history and presentation of a patient with newly-diagnosed, left-sided mCRC.*

*A hypothetical patient profile of treatment for a newly diagnosed mCRC patient.

mCRC = metastatic colorectal cancer.

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EXPLORE PARADIGM POST HOC

IMPORTANT SAFETY INFORMATION

BOXED WARNING:
DERMATOLOGIC TOXICITY

Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC Grade 3 and higher) in 15% of patients receiving Vectibix monotherapy

  • Vectibix® can cause dermatologic toxicity, which may be severe. Clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures.
  • Among 229 patients who received Vectibix® as monotherapy, dermatologic toxicity occurred in 90% including Grade 3 (15%). Among 585 patients who received Vectibix® in combination with FOLFOX, dermatologic toxicity occurred in 96% including Grade 4 (1%) and Grade 3 (32%). In 126 patients receiving Vectibix® in combination with sotorasib across clinical studies, dermatologic toxicities occurred in 94%, including Grade 3 (16%) of patients.
  • Monitor patients who develop dermatologic or soft tissue toxicities while receiving Vectibix® for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix®. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix®. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune- related effects (eg, Stevens Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix® for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix® concerning dermatologic toxicity are provided [see Dosage and Administration (2.3)].
  • Vectibix® monotherapy or in combination with oxaliplatin-based chemotherapy is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as “RAS.”
  • Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents. Additionally, in Study 20050203, 272 patients with RAS-mutant mCRC tumors received Vectibix® in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with RAS-mutant mCRC who received Vectibix® and FOLFOX versus FOLFOX alone.
  • Vectibix® can cause progressively decreasing serum magnesium levels leading to severe (Grade 3 or 4) hypomagnesemia. Among 229 patients who received Vectibix® as monotherapy, hypomagnesemia occurred in 38% including Grade 4 (1.3%) and Grade 3 (2.6%). Among 585 patients who received Vectibix® in combination with FOLFOX, hypomagnesemia occurred in 51% including Grade 4 (5%) and Grade 3 (6%). In 126 patients receiving Vectibix® in combination with sotorasib across clinical studies, decreased magnesium occurred in 69%, including Grade 4 (2.4%) and Grade 3 (14%).
  • Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix® treatment, periodically during Vectibix® treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate.
  • In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC Grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix® administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions.
  • Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix. Among 229 patients who received Vectibix® as monotherapy, acute renal failure occurred in 2% including Grades 3 or 4 (2%). Among 585 patients who received Vectibix® in combination with FOLFOX, acute renal failure occurred in 2% including Grade 3 or 4 (2%). In 126 patients receiving Vectibix® in combination with sotorasib across clinical studies, acute renal failure occurred in 3.2%, including Grade 3 (0.8%). Monitor patients for diarrhea and dehydration, provide supportive care (including anti-emetic or anti‑diarrheal therapy) as needed, and withhold Vectibix® if necessary.
  • Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix. Grade 1 ILD/pneumonitis occurred in 0.8% (1/126) of patients enrolled in clinical studies of Vectibix® in combination with sotorasib. In the event of acute onset or worsening of pulmonary symptoms interrupt Vectibix® therapy. Discontinue Vectibix® therapy if ILD is confirmed.
  • In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix® versus the risk of pulmonary complications must be carefully considered.
  • Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix®.
  • Serious cases of keratitis, ulcerative keratitis, and corneal perforation have occurred with Vectibix® use. Among 585 patients who received Vectibix® in combination with FOLFOX, keratitis occurred in 0.3%. In 126 patients receiving Vectibix® in combination with sotorasib across clinical studies, keratitis occurred in 1.6%, ulcerative keratitis occurred in 0.8%, and vernal keratoconjunctivitis in 0.8% (all were Grade 1-2). Monitor for evidence of keratitis, ulcerative keratitis, or corneal perforation. Interrupt or discontinue Vectibix® therapy for acute or worsening keratitis, ulcerative keratitis, or corneal perforation.
  • In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix® to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC Grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC Grade 3-4 adverse reactions occurring at a higher rate in Vectibix-treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs <1%), and hypomagnesemia (4% vs 0). NCI-CTC Grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix-treated patients (7% vs 3%) and included fatal events in three (< 1%) Vectibix-treated patients.
  • As a result of the toxicities experienced, patients randomized to Vectibix, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy.
  • Based on data from animal studies and its mechanism of action, Vectibix® can cause fetal harm when administered to a pregnant woman. When given during organogenesis, panitumumab administration resulted in embryolethality in cynomolgus monkeys at exposures approximately 1.25 to 5 times the recommended human dose. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of Vectibix®.
  • In monotherapy, the most commonly reported adverse reactions (≥ 20%) in patients with Vectibix® were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea.
  • The most commonly reported adverse reactions (≥ 20%) with Vectibix® + FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. Serious adverse reactions (≥ 2% difference between treatment arms) were diarrhea and dehydration.

Please see Vectibix® full Prescribing Information, including Boxed WARNING.

INDICATION

Vectibix® is indicated for the treatment of adult patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test) metastatic colorectal cancer (mCRC):

  • In combination with FOLFOX for first-line treatment
  • As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.

LIMITATIONS OF USE

Vectibix® is not indicated for the treatment of patients with RAS-mutant mCRC unless used in combination with sotorasib in KRAS G12C-mutated mCRC. Vectibix® is not indicated for the treatment of patients with mCRC for whom RAS mutation status is unknown.

For information about the use of Vectibix® in combination with sotorasib, see Vectibix® Prescribing Information.

Please see Vectibix® full Prescribing Information, including Boxed WARNING.

IMPORTANT SAFETY INFORMATION FOR LUMAKRAS®

  • LUMAKRAS can cause hepatotoxicity and increased ALT or AST which may lead to drug-induced liver injury and hepatitis.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS 960 mg hepatotoxicity occurred in 27% of patients, of which 16% were Grade ≥ 3. Among patients with hepatotoxicity who required dosage modifications, 64% required treatment with corticosteroids.
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS 960 mg, 17% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); of which 9% were Grade ≥ 3. The median time to first onset of increased ALT/AST was 6.3 weeks (range: 0.4 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 9% of patients treated with LUMAKRAS. LUMAKRAS was permanently discontinued due to increased ALT/AST in 2.7% of patients. Drug-induced liver injury occurred in 1.6% (all grades) including 1.3% (Grade ≥ 3).
  • In this pooled safety population of NSCLC patients who received single agent LUMAKRAS 960 mg, a total of 40% patients with recent (≤ 3 months) immunotherapy prior to starting LUMAKRAS had an event of hepatotoxicity. An event of hepatotoxicity was observed in 18% of patients who started LUMAKRAS more than 3 months after last dose of immunotherapy and in 17% of those who never received immunotherapy. Regardless of time from prior immunotherapy, 94% of hepatotoxicity events improved or resolved with dosage modification of LUMAKRAS, with or without corticosteroid treatment.
  • Monitor liver function tests (ALT, AST, alkaline phosphatase and total bilirubin) prior to the start of LUMAKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, reduce the dose or permanently discontinue LUMAKRAS based on severity of the adverse reaction. Consider administering systemic corticosteroids for the management of hepatotoxicity.

Interstitial Lung Disease (ILD)/Pneumonitis

  • LUMAKRAS can cause ILD/pneumonitis that can be fatal.
  • In the pooled safety population of NSCLC patients who received single agent LUMAKRAS 960 mg ILD/pneumonitis occurred in 2.2% of patients, of which 1.1% were Grade ≥ 3, and 1 case was fatal. The median time to first onset for ILD/pneumonitis was 8.6 weeks (range: 2.1 to 36.7 weeks). LUMAKRAS was permanently discontinued due to ILD/pneumonitis in 1.3% of LUMAKRAS-treated patients. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.

Most Common Adverse Reactions

  • The most common adverse reactions ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough.

Drug Interactions

  • Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
  • Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS®.
  • If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS® 4 hours before or 10 hours after a locally acting antacid.

INDICATION

LUMAKRAS® is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.


This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Please see accompanying LUMAKRAS® full Prescribing Information.

IMPORTANT SAFETY INFORMATION

BOXED WARNING:
DERMATOLOGIC TOXICITY

Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC Grade 3 and higher) in 15% of patients receiving Vectibix monotherapy

References

1. Watanabe J, Muro K, Shitara K, et al. JAMA. 2023;329:1271-1282 2. Vectibix® (panitumumab) prescribing information, Amgen. 3. Douillard J-Y, Oliner KS, Siena S, et al. N Engl J Med. 2013;369:1023-1034. 4. AVASTIN® (bevacizumab) prescribing information, Genentech. 5. Ma P, Yang BB, Wang YM, et al. J Clin Pharmacol. 2009;49:1142-1156. 6. Peeters M, Price T, Taieb J, et al. Br J Cancer. 2018;119:303-312. 7. Muro K, Watanabe J, Shitara K, et al. Poster presented at: Annual Meeting of the European Society of Medical Oncology (ESMO); September, 2022; Paris, France. 8.Yoshino, T. Presented at: 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL. 9. Chen D, Li L, Zhang X, et al. Medicine (Baltimore). 2018;97:e0097. 10. Arnold D, Lueza B, Douillard JY, et al. Ann Oncol. 2017;28:1713-1729. 11. Tejpar S, Stintzing S, Ciardiello F, et al. JAMA Oncol. 2017;3;194-201. 12. Loree JM, Dowers A, Tu D, et al. Clin Cancer Res. 2021;27:52-59. 13. Kobayashi Y, Komatsu Y, Yuki S, et al. Future Oncol. 2015;11:617-627.

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